Nanoscale analysis of the interaction between cyanoacrylate and vacuum metal deposition in the development of latent fingermarks on low-density polyethylene.
Vacuum metal deposition (VMD) has been previously demonstrated as an effective development technique for latent fingermarks and in some cases has been shown to enhance prints developed with cyanoacrylate (CA) (superglue) fuming. This work utilizes scanning electron microscopy (SEM) to investigate the interactions of the two development techniques when applied to latent fingermarks on low-density polyethylene. CA is shown to act principally on the eccrine deposits around sweat pores, where polymerization results in long polymer fibrils a few 100 nm in width. Subsequent VMD processing results in additional areas of development, for example, between pores. However, the primary mode of deposition of zinc is by interaction with the polymerized CA, the fibrils of which become decorated with zinc nanoparticles. Areas with limited CA deposition and no significant polymerization are also enhanced with the VMD process, resulting in increased print development.


Ranking in importance of allergen extract characteristics for sublingual immunotherapy by Italian specialists.
The efficacy of allergen immunotherapy (AIT) is well supported by evidence from trials and meta-analyses. However, its actual performance in daily practice may be diminished by several pitfalls, including inappropriate patient selection, and, especially, the use of allergen extracts of insufficient quality. We performed a survey, the Allergen Immunotherapy Decision Analysis, to evaluate which criteria specialists use to choose products for sublingual immunotherapy (SLIT) in adult patients suffering from allergic respiratory disease. We surveyed a total of 169 Italian allergists randomly chosen from a database belonging to a market research company (Lexis Ricerche, Milan, Italy). The survey was performed between October and November 2012 under the aegis of the European Center for Allergy Research Foundation and consisted of a questionnaire-based electronic survey prepared by a scientific board of 12 AIT experts. The questionnaire comprised two parts, the first of which contained 14 items to be ranked by each participant according to the importance assigned to each when choosing SLIT products. The physicians' rankings assigned major importance to the level of evidence-based validation of efficacy and safety, standardization of the product, efficacy based on personal experience, and defined content(s) of the major allergen(s) in micrograms. The results of this survey show that Italian allergists rank the quality-related characteristics of allergen extracts as highly important when choosing products for AIT. The allergists' preference for high-quality products should be addressed by regulatory agencies and by producers.


Fibrinolytic activity after administration of diflunisal and aspirin. A double-blind, randomized, placebo-controlled clinical trial.
A double-blind, randomized, placebo-controlled clinical trial was conducted to determine whether fibrinolysis was increased by the chronic administration of aspirin or diflunisal. Healthy male and female volunteers were randomized to receive either aspirin (1,300 mg every 12 h; 10 subjects), diflunisal (1,000 mg initially, then 500 mg every 12 h; 10 subjects), or placebo (10 subjects) for 8 days. Fibrinolytic activity was examined with the clot lysis assay, using native whole blood, platelet-rich plasma, and platelet-poor plasma, and with the kaolin-activated euglobulin lysis test. In addition, measurements were made of fibrinogen, fibrin/fibrinogen degradation products, plasminogen, and the thrombin time. Clot lysis was greater in whole blood and platelet-rich plasma than in platelet-poor plasma, and increased lysis was observed in specimens obtained in the afternoon as compared to those obtained in the morning. Fibrinolytic activity in the afternoon samples was significantly enhanced by both aspirin and diflunisal at the start of the trial (p less than 0.05), but by the afternoon of day 8, only aspirin showed some enhancement. Fibrinolytic activity, as measured by the euglobulin lysis time, actually declined in all study groups during the course of drug administration. No significant changes were recorded in any of the other assayed hemostatic parameters. We conclude that aspirin and diflunisal exert a modest, nonsustained enhancing effect on fibrinolysis in normal subjects.


Fronting of Southern British English high-back vowels in articulation and acoustics.
The fronting of the two high-back vowels /uː/ and /ʊ/ in Southern British English is very well documented, but mainly in the acoustic domain. This paper presents articulatory (ultrasound) data, comparing the relative tongue position of these vowels in fronting and non-fronting consonantal contexts, i.e., preceding a coronal consonant (food, foot) and preceding a coda /l/ (fool, full). Particular attention is paid to the comparison between articulatory results and corresponding acoustic measurements of F2 in both vowels. Results show that the average differences between food and foot and their dynamic profiles are similar in articulation and acoustics. In /uːl/ sequences (fool), tongue position is more advanced than could be inferred from its low F2. In addition, even though the tongue position in fool and full is clearly distinct, there is no comparable corresponding difference in F2. This suggests that the common articulatory metaphor that characterises F2 increase as fronting must be used cautiously. In the case of English high-back vowel fronting, special attention must be paid to the flanking consonants when estimating vowel distances. This paper also provides specific recommendations for recording and analysing ultrasound data in research on vowel variation and change.


The relation of pericoronal third molar follicle dimension and bcl-2/ki-67 expression: An immunohistochemical study.
Most common impacted teeth are the mandibular third molars and decision about extraction of them is usually controversial. The presence of pericoronal pathologic changes is an acceptable reason for removal of impacted teeth. Differences in the proliferation rate and apoptosis of odontogenic epithelial cells may influence on the formation of odontogenic epithelial lesions. Therefore, the aim of the present study is to evaluate the immunohistochemical expression of the bcl-2 apoptosis-inhibiting protein and the cell-cycle-related ki-67 antigen in pericoronal follicle of impacted third molars with ≥2.5 mm and <2.5 mm radiolucency. This was a cross-sectional study that 20 follicles with <2.5 mm radiolucency and 20 follicles with ≥2.5 mm radiolucency were selected by a professional radiologist in digital panoramic radiographs and then referred to a surgeon. Formalin fixed paraffin-embedded tissues were immunohistochemical analyzed for immunoreactivity of bcl-2 protein and ki-67 antigen. The data was analyzed using logistic regression, Spearman correlation coefficient and t-test and Mann-Whitney. P<0.05 was considered significant. The findings showed correlation between size of the third molar's follicles and expression of bcl-2 protein (P < 0.001, r = 0.556) but there was no correlation between size of third molar's follicles and staining with ki-67 antigen (P = 0.546, r = 0.098). The follicles with radiolucency ≥2.5 mm showed increased immunoreactivity for bcl-2 protein. The results of study suggest that impacted third molars with radiolucency ≥2.5 mm may be associated with deregulation of cell death, indicated with increased expression of the anti- apoptotic protein bcl-2, while cell proliferation (ki-67) does not seem to play a significant role.


Phase Ib Trial of Phenformin in Patients with V600-mutated Melanoma Receiving Dabrafenib and Trametinib.
Preclinical studies show that activation of AMP kinase by phenformin can augment the cytotoxic effect and RAF inhibitors in BRAF V600-mutated melanoma. We conducted a phase Ib dose-escalation trial of phenformin with standard dose dabrafenib/trametinib in patients with metastatic BRAF V600-mutated melanoma. We used a 3+3 dose-escalation design which explored phenformin doses between 50 and 200 mg twice daily. Patients also received standard dose dabrafenib/trametinib. We measured phenformin pharmacokinetics and assessed the effect of treatment on circulating myeloid-derived suppressor cells (MDSC). A total of 18 patients were treated at dose levels ranging from 50 to 200 mg twice daily. The planned dose-escalation phase had to be cancelled because of the COVID 19 pandemic. The most common toxicities were nausea/vomiting; there were two cases of reversible lactic acidosis. Responses were seen in 10 of 18 patients overall (56%) and in 2 of 8 patients who had received prior therapy with RAF inhibitor. Pharmacokinetic data confirmed drug bioavailability. MDSCs were measured in 7 patients treated at the highest dose levels and showed MDSC levels declined on study drug in 6 of 7 patients. We identified the recommended phase II dose of phenformin as 50 mg twice daily when administered with dabrafenib/trametinib, although some patients will require short drug holidays. We observed a decrease in MDSCs, as predicted by preclinical studies, and may enhance immune recognition of melanoma cells. This is the first trial using phenformin in combination with RAF/MEK inhibition in patients with BRAF V600-mutated melanoma. This is a novel strategy, based on preclinical data, to increase pAMPK while blocking the MAPK pathway in melanoma. Our data provide justification and a recommended dose for a phase II trial.


[Experimental study on ototoxicity of cisplatin].
The ototoxicity of cisplatin and a comparison of the ototoxicity between cisplatin and kanamycin had been studied by morphological and biochemical methods. The results showed that the ototoxic effects of both drugs were similar, mainly affecting the cochlea, and next the vestibule. Lesions developed from the periphery to the center. The stria vascularis, the spiral ligament and the secretory epithelium of the vestibule were slightly injured by cis-platin. The K+ and Na+ concentrations of cochlear perilymph changed after the administration of both drugs. The ototoxicity of cis-platin appeared to be accumulated. So, while using cisplatin clinically, we stress the need for careful monitoring of the cochlear and vestibular functions.


Effectiveness of treatment for adolescents and adults with anorexia nervosa in a routine residential setting.
Residential treatment is a necessary element of treatment in some cases of anorexia nervosa, where it is used prior to transitioning to complete the treatment in a less intensive setting. This study tests how effective residential treatment is at helping adolescent and adult patients to reduce their eating pathology to levels that can be managed in outpatient settings. Ninety-eight patients with anorexia nervosa started treatment in a routine residential setting (83 completers). The adolescent and adult groups showed comparable levels of benefit, showing gains in weight and reductions in eating pathology, compatible with transitioning to less intensive treatment. Change was particularly substantial over the first 6 weeks. This effectiveness study has shown that an appropriate period of residential treatment can be used to prepare patients to be able to benefit from a less intensive treatment, regardless of age group.


A Comprehensive Guide to Sleeping Beauty-Based Somatic Transposon Mutagenesis in the Mouse.
Recent advances in whole genome analyses made possible by next-generation DNA sequencing, high-density array comparative genome hybridization (aCGH), and other technologies have made it apparent that cancers harbor numerous genomic changes. However, without functional correlation or validation, it has proven difficult to determine which genetic changes are necessary or sufficient to produce cancer. Thus, it is still necessary to perform unbiased functional studies using model organisms to help interpret the results of whole genome analyses of human tumors. To this end, a Sleeping Beauty (SB) transposon-based mutagenesis technology was developed to identify genes that, when mutated, can cause cancer. Herein a detailed methodology to initiate and carry out an SB transposon mutagenesis screen is described. Although this system might be used to identify genes involved with many cellular phenotypes, it has been primarily implemented for cancer. Thus, SB transposon somatic cell screens for cancer development are highlighted. Curr. Protoc. Mouse Biol. 1:347-368 © 2011 by John Wiley & Sons, Inc.


Human neutrophil elastase inhibition with a novel cotton-alginate wound dressing formulation.
Occlusion and elasticity were combined in a novel cotton-based alginate dressing containing a nontoxic elastase inhibitor. Cotton gauzes were modified with a textile finishing process for incorporating alginate to yield a dressing material that retains elasticity while enhancing absorption. The algino-cellulose conjugates were formed through citric acid crosslinking of cellulose and alginate. The alginate-citrate finishes were applied to cotton gauzes in various formulations containing citric acid, sodium hypophosphite, and polyethylene glycol. The modified gauzes contain a citrate conjugate of alginate and cellulose that gels upon hydration. The alginate-citrate finishes were combined with the neutrophil elastase inhibitor, oleic acid, to demonstrate the ability of the algino-cellulose fibers to release the inhibitor and neutralize destructively high levels of neutrophil elastase found in nonhealing and burn wounds. Four types of gauzes were examined for the effect of the algino-cellulose finish on cotton gauze absorbency and elasticity. Fourier transform infrared (FTIR) spectroscopy of the film and alginate-citrate finished cotton showed formation of the alginate and citrate cellulose esters. Scanning electron microscopy analysis revealed large areas of the yarn surface covered by the alginate film with a smooth surface on the original fibers. Wetting of the gauze surface resulted in formation of a hydrated gel on the yarns with apparent swelling of the film and the fiber-coated alginate.


Disparity in perception of the working condition of dental hygienists between dentists and dental hygiene students in Japan.
In Japan, there continues to be a shortage of active dental hygienists. The scope of dental hygienists' practice is also considered to be unclear. One of the reasons for this is that dental hygienists find the working conditions during dental hygiene education different from those in reality. The purpose of this study was to clarify the actual working condition of dental hygienists in dental clinics, as well as evaluate the awareness of dental hygiene students and dentists regarding the working condition of dental hygienists. Questionnaires were sent by post to 481 dentists and were distributed to 89 dental hygiene students. The awareness about the working condition of dental hygienists was compared between dentists and dental hygiene students. Two hundred twenty-two dentists and 89 dental hygiene students responded to questionnaires. Dental hygiene students considered the team of 'dental hygienist, dental technician and clerk' to be more effective in providing dental care than dentists (P < 0.001). Among the dentists, 37.1% did not find any clear distinction between hygienists and assistants in their clinics. However, 97.4% of dental hygiene students answered that dental team members should clearly inform patients of the distinction between hygienists and assistants. This study indicated that there was disparity between dentists' and dental hygiene students' perception of dental hygienists' working conditions, and dental team work was not always effective. For training high quality dental hygienists, all educational institutions related to dentistry must educate students regarding the more realistic dental hygienists' working condition, as well as benefits.


Cerebrospinal and Blood Biomarkers in Alzheimer's Disease: Did Mild Cognitive Impairment Definition Affect Their Clinical Usefulness?
Despite Alzheimer's Disease (AD) being known from the times of Alois Alzheimer, who lived more than one century ago, many aspects of the disease are still obscure, including the pathogenesis, the clinical spectrum definition, and the therapeutic approach. Well-established biomarkers for AD come from the histopathological hallmarks of the disease, which are Aβ and phosphorylated Tau protein aggregates. Consistently, cerebrospinal fluid (CSF) Amyloid β (Aβ) and phosphorylated Tau level measurements are currently used to detect AD presence. However, two central biases affect these biomarkers. Firstly, incomplete knowledge of the pathogenesis of diseases legitimates the search for novel molecules that, reasonably, could be expressed by neurons and microglia and could be detected in blood simpler and earlier than the classical markers and in a higher amount. Further, studies have been performed to evaluate whether CSF biomarkers can predict AD onset in Mild Cognitive Impairment (MCI) patients. However, the MCI definition has changed over time. Hence, the studies on MCI patients seem to be biased at the beginning due to the imprecise enrollment and heterogeneous composition of the miscellaneous MCI subgroup. Plasma biomarkers and novel candidate molecules, such as microglia biomarkers, have been tentatively investigated and could represent valuable targets for diagnosing and monitoring AD. Also, novel AD markers are urgently needed to identify molecular targets for treatment strategies. This review article summarizes the main CSF and blood AD biomarkers, underpins their advantages and flaws, and mentions novel molecules that can be used as potential biomarkers for AD.


Translating the hierarchical taxonomy of psychopathology (HiTOP) from potential to practice: Ten research questions.
The Hierarchical Taxonomy of Psychopathology (HiTOP) is a novel diagnostic system grounded in empirical research into the architecture of mental illness. Its basic units are continuous dimensions-as opposed to categories-that are organized into a hierarchy according to patterns of symptom co-occurrence observed in quantitative studies. Previous HiTOP discussions have focused on existing evidence regarding the model's structure and ability to account for neurobiological, social, cultural, and clinical variation. The present article looks ahead to the next decade of applied research and clinical practice using the HiTOP rubric. We highlight 10 topics where HiTOP has the potential to make significant breakthroughs. Research areas include genetic influences, environmental contributions, neural mechanisms, real-time dynamics, and lifespan development of psychopathology. We also discuss development of novel assessments, forecasting methods, and treatments. Finally, we consider implications for clinicians and educators. For each of these domains, we propose directions for future research and venture hypotheses as to what HiTOP will reveal about psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Medaka spalt acts as a target gene of hedgehog signaling.
In vertebrates, pattern formation in the eye, central nervous system, somites, and limb depends on hedgehog activity, but a general target gene controlled by hedgehog in all these signaling centers has remained largely elusive. The medaka fish gene spalt encodes a zinc-finger transcription factor, which is expressed in all known hedgehog signaling centers of the embryo and in the organizer region at the midbrain-hindbrain boundary. We show that the spalt expression domains expand in response to ectopic hedgehog activity and narrow in the presence of protein kinase A activity, an antagonist of hedgehog signaling, indicating that spalt is a hedgehog target gene. Our results also suggest a signaling mechanism for anterior-posterior patterning of the vertebrate brain that controls spalt expression at the midbrain-hindbrain boundary in a protein kinase A dependent manner likely to involve an unknown member of the hedgehog family.


Children's literature for the primary inclusive classroom: increasing understanding of children with hearing impairments.
As a result of recent federal legislation and positive research findings of educators, children with disabilities, including hearing impairment, are being included in general education classrooms. This development has many implications at the state, district, and classroom levels. While helping the child with disabilities assimilate into the general education classroom may appear to be the teacher's primary challenge, increasing awareness and understanding among those students without disabilities is a growing concern of educators. The use of children's literature featuring children with disabilities is one way to promote this understanding. This article includes an annotated bibliography of children's literature featuring children with hearing impairment, along with related classroom activities to enhance experiences with the books.


People with higher autistic traits show stronger binding for color-shape associations.
Non-synesthetes exhibit a tendency to associate specific shapes with particular colors (i.e., circle-red, triangle-yellow, and square-blue). Such color-shape associations (CSAs) could potentially affect the feature binding of colors and shapes, thus resulting in people reporting more binding errors in the case of incongruent, rather than congruent, colored-shape pairs. Individuals with autism spectrum disorder (ASD) exhibit atypical sensory processing and impaired multisensory integration. Here, we examined whether autistic traits (Autism-Spectrum Quotient; AQ) influence the strength of color-shape associations, as evidenced by the occurrence of binding errors in incongruent minus congruent conditions. Participants took part in an experiment designed to reveal binding errors induced by incongruent and congruent colored-shape pairs, and completed the Japanese version of the AQ score. The results revealed a significant correlation between AQ scores and occurrence of binding errors when participants were presented with the circle-red and triangle-yellow CSAs: That is, individuals with higher autistic traits tend to make more binding errors in incongruent minus congruent colored-shape pairs, indicating a stronger binding of circle-red and triangle-yellow associations. These results therefore suggest that autistic traits play a role in forming color-shape associations, shedding light on the nature of both color-shape associations and autistic perception.


Autophagosome supports coxsackievirus B3 replication in host cells.
Recent studies suggest a possible takeover of host antimicrobial autophagy machinery by positive-stranded RNA viruses to facilitate their own replication. In the present study, we investigated the role of autophagy in coxsackievirus replication. Coxsackievirus B3 (CVB3), a picornavirus associated with viral myocarditis, causes pronounced intracellular membrane reorganization after infection. We demonstrate that CVB3 infection induces an increased number of double-membrane vesicles, accompanied by an increase of the LC3-II/LC3-I ratio and an accumulation of punctate GFP-LC3-expressing cells, two hallmarks of cellular autophagosome formation. However, protein expression analysis of p62, a marker for autophagy-mediated protein degradation, showed no apparent changes after CVB3 infection. These results suggest that CVB3 infection triggers autophagosome formation without promoting protein degradation by the lysosome. We further examined the role of the autophagosome in CVB3 replication. We demonstrated that inhibition of autophagosome formation by 3-methyladenine or small interfering RNAs targeting the genes critical for autophagosome formation (ATG7, Beclin-1, and VPS34 genes) significantly reduced viral replication. Conversely, induction of autophagy by rapamycin or nutrient deprivation resulted in increased viral replication. Finally, we examined the role of autophagosome-lysosome fusion in viral replication. We showed that blockage of the fusion by gene silencing of the lysosomal protein LAMP2 significantly promoted viral replication. Taken together, our results suggest that the host's autophagy machinery is activated during CVB3 infection to enhance the efficiency of viral replication.


Visual hallucinations in Alzheimer's disease is significantly associated with clinical diagnostic features of dementia with Lewy bodies.
Visual hallucinations (VHs) are among the most striking features of dementia with Lewy bodies (DLB). Given that Lewy body pathology is frequently observed in the brains of patients with AD, we aimed to study factors associated with VHs in AD and examine their association with DLB features. This cross-sectional study enrolled a consecutive series of AD patients who visited the dementia clinic of a regional hospital. Clinically diagnosed possible or probable DLB cases were excluded. VH frequency and associated factors including age, sex, education, disease severity, DLB features, vascular risk factors, cognitive function, and neuropsychiatric symptoms were compared between AD patients with VHs (VH+) and those without VHs (VH-). Among a total of 295 patients analyzed, 42 (14.2%) had VHs. After adjusting for age, sex, and disease severity, DLB features including fluctuations in cognition scores, rapid-eye-movement behavioral disorder (RBD), and severe neuroleptic sensitivity were more frequent in the VH+ group. Furthermore, depression score, total Neuropsychiatric Inventory (NPI) score, and total caregiver burden score as assessed by the NPI were higher in the VH+ group. Among neuropsychiatric symptoms, delusions, hallucinations in the non-visual domains, anxiety, and disinhibition were more frequent in the VH+ group. Conversely, none of the vascular risk factors (VRFs) or cognitive domains of the Cognitive Abilities Screening Instrument (CASI) was associated with VHs in AD. In summary, VHs, albeit occurring at a low rate, had a high impact on AD. Diagnostic features of DLB, including fluctuations, RBD, and severe neuroleptic sensitivity were significantly associated with VHs in AD. AD patients with VHs tended to have more severe neuropsychiatric symptoms and greater caregiver burden.


Collision detection for moving polyhedra.
We consider the collision-detection problem for a three-dimensional solid object moving among polyhedral obstacles. The configuration space for this problem is six-dimensional, and the traditional representation of the space uses three translational parameters and three angles (typically Euler angles). The constraints between the object and obstacles then involve trigonometric functions. We show that a quaternion representation of rotation yields constraints which are purely algebraic in a seven-dimensional space. By simple manipulation, the constraints may be projected down into a six-dimensional space with no increase in complexity. The algebraic form of the constraints greatly simplifies computation of collision points, and allows us to derive an efficient exact intersection test for an object which is translating and rotating among obstacles.


Vitamin D status during pregnancy and the risk of subsequent postpartum depression: a case-control study.
Epidemiological studies have provided evidence of an association between vitamin D insufficiency and depression and other mood disorders, and a role for vitamin D in various brain functions has been suggested. We hypothesized that low vitamin D status during pregnancy might increase the risk of postpartum depression (PPD). The objective of the study was thus to determine whether low vitamin D status during pregnancy was associated with postpartum depression. In a case-control study nested in the Danish National Birth Cohort, we measured late pregnancy serum concentrations of 25[OH]D3 in 605 women with PPD and 875 controls. Odds ratios [OR) for PPD were calculated for six levels of 25[OH]D3. Overall, we found no association between vitamin D concentrations and risk of PPD (p = 0.08). Compared with women with vitamin D concentrations between 50 and 79 nmol/L, the adjusted odds ratios for PPD were 1.35 (95% CI: 0.64; 2.85), 0.83 (CI: 0.50; 1.39) and 1.13 (CI: 0.84; 1.51) among women with vitamin D concentrations < 15 nmol/L, 15-24 nmol/L and 25-49 nmol/L, respectively, and 1.53 (CI: 1.04; 2.26) and 1.89 (CI: 1.06; 3.37) among women with vitamin D concentrations of 80-99 nmol/L and ≥ 100 nmol/L, respectively. In an additional analysis among women with sufficient vitamin D (≥ 50 nmol/L), we observed a significant positive association between vitamin D concentrations and PPD. Our results did not support an association between low maternal vitamin D concentrations during pregnancy and risk of PPD. Instead, an increased risk of PPD was found among women with the highest vitamin D concentrations.


OXA-46, a new class D beta-lactamase of narrow substrate specificity encoded by a blaVIM-1-containing integron from a Pseudomonas aeruginosa clinical isolate.
A novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette inserted into a class 1 integron from a multidrug-resistant Pseudomonas aeruginosa clinical isolate. The variable region of the integron also contained a bla(VIM-1) metallo-beta-lactamase cassette and a duplicated aacA4 aminoglycoside acetyltransferase cassette. OXA-46 belongs to the OXA-2 lineage of class D beta-lactamases. It exhibits 78% sequence identity with OXA-2 and the highest similarity (around 92% identity) with another OXA-type enzyme detected in clinical isolates of Burkholderia cepacia and in unidentified bacteria from a wastewater plant. Expression of bla(OXA-46) in Escherichia coli decreased susceptibility to penicillins and narrow-spectrum cephalosporins but not to extended-spectrum cephalosporins, cefsulodin, aztreonam, or carbapenems. The enzyme was overproduced in E. coli and purified by two anion-exchange chromatography steps (approximate yield, 6 mg/liter). OXA-46 was made of a 28.5-kDa polypeptide and exhibited an alkaline pI (7.8). In its native form OXA-46 appeared to be dimeric, and the oligomerization state was not affected by EDTA. Kinetic analysis of OXA-46 revealed a specificity for narrow-spectrum substrates, including oxacillin, other penicillins (but not temocillin), and narrow-spectrum cephalosporins. The enzyme apparently did not interact with temocillin, oxyimino-cephalosporins, or aztreonam. OXA-46 was inactivated by tazobactam and carbapenems and, although less efficiently, also by clavulanic acid. Enzyme activity was not affected either by EDTA or by divalent cations and exhibited low susceptibility to NaCl. These findings underscore the functional and structural diversity that can be encountered among class D beta-lactamases.


The molecular basis for ANE syndrome revealed by the large ribosomal subunit processome interactome.
ANE syndrome is a ribosomopathy caused by a mutation in an RNA recognition motif of RBM28, a nucleolar protein conserved to yeast (Nop4). While patients with ANE syndrome have fewer mature ribosomes, it is unclear how this mutation disrupts ribosome assembly. Here we use yeast as a model system and show that the mutation confers growth and pre-rRNA processing defects. Recently, we found that Nop4 is a hub protein in the nucleolar large subunit (LSU) processome interactome. Here we demonstrate that the ANE syndrome mutation disrupts Nop4's hub function by abrogating several of Nop4's protein-protein interactions. Circular dichroism and NMR demonstrate that the ANE syndrome mutation in RRM3 of human RBM28 disrupts domain folding. We conclude that the ANE syndrome mutation generates defective protein folding which abrogates protein-protein interactions and causes faulty pre-LSU rRNA processing, thus revealing one aspect of the molecular basis of this human disease.


Effect Transformation of the Micro Electrode Recording (MER) Data to Fast Fourier Transform (FFT) for the Main Target Nucleus Determination for STN-DBS.
Advanced PD stimulation of the STN reduces tremor, rigidity, and bradykinesia. Due to hemorrhagic complications the use of micro electrode recordings during DBS operation was still questioning for some of surgeons. But use micro electrodes were still the best choice for the positioning during surgery of DBS. The aim of the current study was to investigate the effect transformation of the micro electrode recording data to fast fourier transform for the main target nucleus determination. This process needs a multidisciplinary approach from neurosurgery, neurology and specialists on electrophysiology such as biophysics. We present the case of a 63 year-old male with medically intractable PD is focused on behalf of the surgical treatment. Patient had a 4-year history of progressively severe hand tremor on right side. The patient was successfully treated unilaterally with the STN DBS.


Depletion of nuclear histone H2A variants is associated with chronic DNA damage signaling upon drug-evoked senescence of human somatic cells.
Cellular senescence is associated with global chromatin changes, altered gene expression, and activation of chronic DNA damage signaling. These events ultimately lead to morphological and physiological transformations in primary cells. In this study, we show that chronic DNA damage signals caused by genotoxic stress impact the expression of histones H2A family members and lead to their depletion in the nuclei of senescent human fibroblasts. Our data reinforce the hypothesis that progressive chromatin destabilization may lead to the loss of epigenetic information and impaired cellular function associated with chronic DNA damage upon drug-evoked senescence. We propose that changes in the histone biosynthesis and chromatin assembly may directly contribute to cellular aging. In addition, we also outline the method that allows for quantitative and unbiased measurement of these changes.


Bioinformatics tools and data resources for assay development of fluid protein biomarkers.
Fluid protein biomarkers are important tools in clinical research and health care to support diagnosis and to monitor patients. Especially within the field of dementia, novel biomarkers could address the current challenges of providing an early diagnosis and of selecting trial participants. While the great potential of fluid biomarkers is recognized, their implementation in routine clinical use has been slow. One major obstacle is the often unsuccessful translation of biomarker candidates from explorative high-throughput techniques to sensitive antibody-based immunoassays. In this review, we propose the incorporation of bioinformatics into the workflow of novel immunoassay development to overcome this bottleneck and thus facilitate the development of novel biomarkers towards clinical laboratory practice. Due to the rapid progress within the field of bioinformatics many freely available and easy-to-use tools and data resources exist which can aid the researcher at various stages. Current prediction methods and databases can support the selection of suitable biomarker candidates, as well as the choice of appropriate commercial affinity reagents. Additionally, we examine methods that can determine or predict the epitope - an antibody's binding region on its antigen - and can help to make an informed choice on the immunogenic peptide used for novel antibody production. Selected use cases for biomarker candidates help illustrate the application and interpretation of the introduced tools.


Musculoskeletal abnormalities of the tibia in juvenile rheumatoid arthritis.
To characterize local bone geometry, density, and strength, using peripheral quantitative computed tomography (pQCT), compared with general bone characteristics as measured using dual x-ray absorptiometry (DXA), and to assess their relationship to disease-related factors in children with juvenile rheumatoid arthritis (JRA). Forty-eight children ages 4-18 years with JRA (17 pauciarticular, 23 polyarticular, 8 systemic) were compared with age-matched healthy controls (n = 266). Measurements included cortical and trabecular bone geometry, density, and strength at the distal and midshaft tibia determined by pQCT, and whole-body, lumbar spine, and femoral neck measurements by DXA. Methotrexate (MTX) was prescribed to 23 of 48 patients (47.9%) and glucocorticoids and MTX were prescribed to 15 of 48 patients (31.3%), with the greatest use in children with systemic JRA. All JRA patients had decreased tibia trabecular bone density, cortical bone size and strength, and muscle mass. Children with systemic JRA had lower femoral neck densities. Systemic JRA was associated with a shorter, less mineralized skeleton, while a narrower, less mineralized skeleton was observed in polyarticular JRA. The tibia diaphysis was narrower with decreased muscle mass, but normal, size-adjusted bone mineral in all subtypes indicated a localized effect of JRA on bone. Patients exposed to glucocorticoids and MTX or to glucocorticoids or MTX alone had greatly reduced trabecular density, cortical bone geometry properties, and bone mineral content, muscle mass, and bone strength. Children with JRA have decreased skeletal size, muscle mass, trabecular bone density, cortical bone geometry, and strength. Not surprisingly, these bone abnormalities are more pronounced in children with greater disease severity.


Relationship between negative experiences and drinking experience among 15- to 16-year-old adolescents in Finland.
To assess the relationship between negative experiences and frequency of alcohol drinking and drunkenness among 15- to 16-year-old adolescents in Finland. A school-based survey as part of the European School Project on Alcohol and Other Drugs (ESPAD) conducted in Finland in 2003. Nationally representative sample of Finnish adolescents, aged 15-16 (n = 3,321). Response rate 92%. Negative experiences, alcohol use and drunkenness were assessed using a self-administered questionnaire. Logistic regression analysis was used to examine the relationship between negative experiences and drinking experience. Prevalence of negative experiences increased with increased frequency of drinking and drunkenness. Certain harms (troubles with the police, engaging in regretted and unprotected sexual intercourse) were experienced primarily with frequent drinking and drunkenness (>20 occasions). Logistic regression analysis indicated that only the drunkenness-related drinking style was significantly related to troubles with the police and engaging in sexual intercourse regretted the next day. While under-aged youths experience many problems in relationship to their alcohol use, certain problems are highly associated with frequent and heavy drinking, especially with drunkenness-related drinking style. These findings should be acknowledged when implementing effective alcohol education and alcohol-related policies to reduce under-aged alcohol use and related harms.


1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose increases a population of T regulatory cells and inhibits IgE production in ovalbumin-sensitized mice.
1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) is a gallotannin isolated from various plants. In a previous study, it was reported that PGG suppressed interleukin (IL)-4 induced signal pathway in B cell which is indispensable for immunoglobulin E (IgE) production. However, the suppressive effect of PGG on IgE production in allergen-sensitized mice remains unclear. Therefore, the aim of this study was to investigate the inhibitory effect of PGG on IgE production in ovalbumin (OVA)-sensitized mice. Mice orally administered PGG showed a decrease in total and OVA-specific IgE levels in serum. Oral administration of PGG strongly suppressed production of type 2 T helper (IL-4 and IL-13), type 1 T helper (IFN-γ), and pro-inflammatory cytokines (TNF-α and IL-6), but not anti-inflammatory cytokine (IL-10) from splenocytes of OVA-sensitized mice against OVA re-stimulation. A population of T regulatory (Treg) cells with immunosuppressive properties was increased in mesenteric lymph nodes and spleen of PGG-fed mice. PGG administration not only reduced expression levels of eotaxin, tissue inhibitors of metalloproteinases-1, and TNF-α, which assisted with IgE production, but also increased the expression of insulin-like growth factor binding protein-3 which inhibits IgE production. Additionally, PGG increased the levels of Treg cell-inducing factors such as IL-2, IL-10 and platelet factor-4 in serum. These data suggest that the inhibitory effect of PGG on IgE production could be partially caused by increasing a population of Treg cells in conjunction with Treg-inducing factors.


Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial.
A deficit of mitochondrial energy metabolism may play a role in migraine pathogenesis. We found in a previous open study that high-dose riboflavin was effective in migraine prophylaxis. We now compared riboflavin (400 mg) and placebo in 55 patients with migraine in a randomized trial of 3 months duration. Using an intention-to-treat analysis, riboflavin was superior to placebo in reducing attack frequency (p = 0.005) and headache days (p = 0.012). Regarding the latter, the proportion of patients who improved by at least 50%, i.e. "responders," was 15% for placebo and 59% for riboflavin (p = 0.002) and the number-needed-to-treat for effectiveness was 2.3. Three minor adverse events occurred, two in the riboflavin group (diarrhea and polyuria) and one in the placebo group (abdominal cramps). None was serious. Because of its high efficacy, excellent tolerability, and low cost, riboflavin is an interesting option for migraine prophylaxis and a candidate for a comparative trial with an established prophylactic drug.


Australasian emergency nurses' willingness to attend work in a disaster: a survey.
The type of disaster, individual demographic factors, family factors and workplace factors, have been identified in the international, multidisciplinary literature as factors that influence a person's willingness to attend and assist in their workplace during a disaster. However, it is unknown if these factors are applicable to Australasian emergency nurses. The research aims to determine the extent to which Australasian emergency nurses are willing to attend their workplace in a disaster. This research was exploratory and descriptive study design, using online and paper based surveys as a means of data collection. Australasian emergency nurses from two Australasian emergency nursing colleges and four Australian hospitals were recruited to participate. Data analysis was conducted using both descriptive and inferential statistics. In total, 451 Australasian emergency nurses participated in this research. Participants were more willing to attend their workplace during a conventional disaster (p ≤ 0.001), if they worked full-time (p = 0.01), had received formal education pertaining to disasters (p ≤ 0.001), had a family disaster plan (p = 0.008), did not have children (p = 0.001) and worked in an environment in which they perceived their colleagues, managers and organisation to be prepared. The factors that influenced Australasian emergency nurses to attend their workplace in a disaster were similar to that described in the international multidisciplinary literature. Of particular note, improving disaster knowledge and skills, having a family disaster plan and improving the perceptions of the nurses' workplace preparedness can enhance the nurses' willingness to assist in a disaster.


Citizen Preferences for Primary Health Care reform in Greece.
The Greek National Health System is currently pursuing the strengthening of Primary Health Care (PHC). Citizen preferences for healthcare service utilization, their views on structural reform of the current system, and the profiling of those in favor of PHC are essential in planning a reform that respects citizens' needs. However, data on this topic in the country are scarce. The present study maps citizen preferences for health care reform in the primary care sector in Greece. In March 2017, a sample of 1,002 citizens were surveyed by telephone. The survey was repeated with a different sample of 1,001 persons in October 2017. Both samples were defined via a random multistage selection process using a quota for the municipality of residence, sex, and age. Responders were asked to rate their satisfaction with the existing healthcare system and to rank their preferences as to the most important elements of future structural reform. Barriers to accessing healthcare services and in the implementation of structural reform as well as actual healthcare services utilization were also recorded. A logistic regression model was used to identify sample characteristics independently associated with the most requested reform. Citizens preferred to visit physicians -as outpatients- in their private practices (50.5 % in March and 44 % in October) rather than in public health services (17.8 % and 18 %, respectively). For 86.9 % and 85.6 %, respectively, structural reform of the current health system was considered "very" or "extremely necessary". The introduction of family physicians in the system was the most requested reform (48 % and 49.4 %, respectively). Citizens in older age groups were more likely to request the implementation of family physicians (25-39 years old: OR: 2.14, 95 % CI: 1.36-3.37; 40-54 years old: OR: 2.89, 95 % CI: 1.85-4.52; 55-64 years old: OR: 3.62, 95 % CI: 2.27-5.78; and over 65 years old: OR: 3.32, 95 % CI: 2.10-5.26). Male responders were 23 % less likely (OR: 0.77, 95 % CI: 0.63-0.93) to be in favor of this reform, after controlling for the other variables in the model. Both survey streams reveal the growing demand for structural reform in the current healthcare system. Strengthening PHC is the most requested reform. Older and female citizens were more likely to be in favor of this reform. Integrating the private sector in developing a comprehensive PHC system, enhancing existing public health services, and increasing public awareness of the advantages of PHC should be considered critical elements of a high-quality PHC system. HIPPOKRATIA 2019, 23(3): 111-117.


JEMs and incompatible occupational coding systems: effect of manual and automatic recoding of job codes on exposure assignment.
In epidemiological studies, occupational exposure estimates are often assigned through linkage of job histories to job-exposure matrices (JEMs). However, available JEMs may have a coding system incompatible with the coding system used to code the job histories, necessitating a translation of the originally assigned job codes. Since manual recoding is usually not feasible in large studies, this is often done by use of automated crosswalks translating job codes from one system to another. We set out to investigate whether automatically translating job codes led to different exposure estimates compared with those resulting from manual recoding using the original job descriptions. One hundred job histories were randomly drawn from the Netherlands Cohort Study on diet and cancer (NLCS), using a sampling strategy designed to oversample potentially exposed jobs. This resulted in 220 job codes that were automatically translated from the original Dutch coding system to the International Standard Classification of Occupations (ISCO)-68 and ISCO-88 as well as manually recoded from the job descriptions in the original questionnaire by two coders. Exposure to several agents (i.e. chromium, asbestos, silica, pesticides, aromatic solvents, and extremely low-frequency magnetic fields) was assigned by JEMs based on job codes resulting from automatic and manual recodings. The agreement between occupational exposure estimates based on the crosswalk versus those based on manual recoding reached a Cohen's Kappa (κ) of 0.66 or higher and were similar to the agreements between the two coders. Results of this study indicate that using automated crosswalks to recode job codes from one occupational classification system to another results only in a limited loss in agreement in assigned occupational exposure estimates compared with direct manual recoding. Therefore, in this case, crosswalks provide an efficient alternative to the costly and time-consuming direct manual recoding from job history descriptions from questionnaires.


In Vitro Evaluation of Sulforaphane and a Natural Analog as Potent Inducers of 5-Fluorouracil Anticancer Activity.
Isothiocyanates (R-NCS) are sulphur-containing phytochemicals. The main source are plants of the Brassicaceae family. The best known plant-derived isothiocyanate is sulforaphane that has exhibited anticancer activity in both in vivo and in vitro studies. Recent attempts to expand their use in cancer therapy involve combining them with standard chemotherapeutics in order to increase their therapeutic efficacy. The aim of this paper is to determine the impact of sulforaphane and its natural analog alyssin on the anticancer activity of the well-known anticancer drug 5-fluorouracil. The type of drug-drug interactions was determined in prostate and colon cancer cell lines. Confocal microscopy, western blot and flow cytometry methods were employed to determine the mechanism of cytotoxic and cytostatic action of the combinations. The study revealed that additive or synergistic interactions were observed between 5-fluorouracil and both isothiocyanates, which enhanced the anticancer activity of 5-fluorouracil, particularly in colon cancer cell lines. An increased cytostatic effect was observed in case of alyssin while for sulforaphane the synergistic interaction with 5-fluorouracil involved an intensification of apoptotic cell death.


[Study on the changing regularity of special antibody and expression of stomach and enteric involvement on SARS-coronavirus infection in the recovery period of severe acute respiratory syndrome].
To study the change of special antibodies titer IgG, IgM and nucleocapsid to SARS coronavirus (CoV) and observing the expression of stomach and enteric involvement on SARS-CoV infection by monoclonal antibody against N protein of SARS-CoV in the 7-year recovery period among family clustering cases of severe acute respiratory syndrome. Special antibody titer to SARS-CoV of 14 patients from 5 different families and their 10 kinfolks continuously tested by IFA and antigen-capturing ELISA methods. Samples were taken in the 1(st) - 7(th) year periods after SARS patients infected by SARS-CoV, being diluted and measured on it titers of three kinds of antibodies. Immunochemical staining with monoclonal antibody (mAb) against N protein of SARS-CoV was used to determine the stomach and enteric tissues among 5 SARS patients with their nucleocapsid antibody titer ascended obviously after 1(st)-7(th) year. When testing the IgG antibody titer of the 14 SARS patients by IFA method, the average titer was 1/71 (95%CI: 1/58 - 1/85) in the 1(st) year, but began to descend in the following years, and the IgG antibody of the most SARS patients disappeared in the 7(th) year. Regarding the IgM titer, it disappeared in most of the SARS patients 1 year later. The average value of nucleocapsid antibody titer was 1/146 (95%CI: 1/122 - 1/171) in the 1(st) year, and it descended as the IgG antibody titer did. In 5 cases, differences appeared. The nucleocapsid antibody titer was between 1/156 and 1/210 in 3 cases, and 2 cases were normal. Immunochemical staining with mAb against N protein of SARS-CoV was identified in the stomach and enteric tissues of 5 SARS patients with the nucleocapsid antibody titer increased significantly, 1(st)-7(th) year later. The five patients were detected by gastroscopy detection and cell immunohistochemistry test. 3 cases showed N protein antibody positive in the serum, and positive immunohistochemical expression in most of the cytoplasm in the gastric tissue mucous gland epithelial cells. 1 case also expressed in the intestinal tissue slurry columnar epithelium and interstitial cells. The other two cases showed negative on both serum N protein antibody and immunohistochemical expression. The biopsy results of the 5 patients were as follows: 1 case diagnosed as "signet-ring cell carcinoma of the stomach and rectum multiple transfer", 1 case of gastric polyp, 1 case of superficial antral gastritis and 2 cases were normal. By testing the special IgG, IgM, nucleocapsid antibody to SARS-CoV of the 14 family clustering cases, we found that they all decreased in the 7(th) year, and most of them disappeared. The nucleocapsid antibody titer was related to pathogenetic condition. SARS-CoV was proved to be still present in stomach and enteric tissues of SARS patients with the nucleocapsid antibody titer increased significantly after the 7(th) year.


Breaking down silos: engaging students to help fix the US health care system.
The field of health care is becoming a team effort as patient care becomes increasingly complex and multifaceted. Despite the need for multidisciplinary education, there persists a lack of student engagement and collaboration among health care disciplines, which presents a growing concern as students join the workforce. In October 2013, the Emory-Georgia Tech Healthcare Innovation Program organized a student driven symposium entitled "US Healthcare: What's Broken and How to Fix It: The Student Perspective". The symposium engaged students from multiple disciplines to work together in addressing problems associated with US health care delivery. The symposium was organized and carried out by a diverse group of student leaders from local institutions who adopted a multidisciplinary approach throughout the planning process. The innovative planning process leading up to the symposium revealed that many of the student-discipline groups lacked an understanding of one another's role in health care, and that students were interested in learning how to work together to leverage each other's profession. The symposium was widely attended and positively received by students and faculty from the Atlanta metropolitan area, and has since helped to promote interdepartmental collaboration and multidisciplinary education across institutions. The student symposium will become an annual event and incorporate broader discipline representation, as well as a patient perspective. Proposals for additional institution-wide, multidisciplinary educational offerings are being addressed with the help of faculty and health care providers across the network. Accordingly, the implementation of student-driven symposia to engage students and stimulate institution-wide changes may be a beneficial and cost-effective means for academic health centers looking to facilitate multidisciplinary health care education.


The PEDtracker: An Automatic Staging Approach for Drosophila melanogaster Larvae.
The post-embryonal development of arthropod species, including crustaceans and insects, is characterized by ecdysis or molting. This process defines growth stages and is controlled by a conserved neuroendocrine system. Each molting event is divided in several critical time points, such as pre-molt, molt, and post-molt, and leaves the animals in a temporarily highly vulnerable state while their cuticle is re-hardening. The molting events occur in an immediate ecdysis sequence within a specific time window during the development. Each sub-stage takes only a short amount of time, which is generally in the order of minutes. To find these relatively short behavioral events, one needs to follow the entire post-embryonal development over several days. As the manual detection of the ecdysis sequence is time consuming and error prone, we designed a monitoring system to facilitate the continuous observation of the post-embryonal development of the fruit fly Drosophila melanogaster. Under constant environmental conditions we are able to observe the life cycle from the embryonic state to the adult, which takes about 10 days in this species. Specific processing algorithms developed and implemented in Fiji and R allow us to determine unique behavioral events on an individual level-including egg hatching, ecdysis and pupation. In addition, we measured growth rates and activity patterns for individual larvae. Our newly created RPackage PEDtracker can predict critical developmental events and thus offers the possibility to perform automated screens that identify changes in various aspects of larval development. In conclusion, the PEDtracker system presented in this study represents the basis for automated real-time staging and analysis not only for the arthropod development.


A New Prognostic Instrument Specifically Designed for Patients Irradiated for Recurrent Carcinoma of the Bladder.
To develop an instrument that could estimate the 1-year survival probabilities of patients irradiated for recurrent carcinoma of the bladder. Thirty patients irradiated for locally recurrent bladder carcinoma were included. Six pre-treatment factors [age, gender, Karnofsky score (KPS), pack years, grading and time between cancer diagnosis and radiotherapy] were evaluated for survival. Of those factors showing a trend or significance on multivariate analysis, 1-year survival rates were added. On multivariate analysis, KPS was significant (hazard ratio(HR)=3.76, p=0.008), age showed a trend (HR=2.04, p=0.13). Patient scores were five, nine, ten or fourteen points with 1-year survival rates of 13%, 25%, 57% and 82% (p=0.003). Three groups were designed, A (5-9 points), B (10 points) and C (14 points) with 1-year survival rates of 17%, 57% and 82% (p=0.001). This score, including three groups with different 1-year survival probabilities, can aid physicians treating patients with recurrent bladder carcinoma.


Using Organizational Philosophy to Create a Self-Sustaining Compensation Plan Without Harming Academic Missions.
Academic physician reimbursement has moved to productivity-based compensation plans. To be sustainable, such plans must be self-funding. Additionally, unless research and education are appropriately valued, faculty involved in these efforts will become disillusioned, yet revenue generation in these activities is less robust than for clinical care activities. Faculty at the Department of Medicine, University of Florida Health, elected a committee of junior and senior faculty and division chiefs to restructure the compensation plan in fiscal year (FY) 2011. This committee was charged with designing a new compensation plan based on seven principles of organizational philosophy: equity, compensation coupled to productivity, authority aligned with responsibility, respect for all academic missions, transparency, professionalism, and self-funding in each academic mission. The new compensation plan was implemented in FY2013. A survey administered at the end of FY2015 showed that 61% (76/125) of faculty were more satisfied with this plan than the previous plan. Since the year before implementation, clinical relative value units per faculty increased 7% (from 3,458 in FY2012 to 3,704 in FY2015, P < .002), incentives paid per faculty increased 250% (from $3,191 in FY2012 to $11,153 in FY2015, P ≤ .001), and publications per faculty increased 15% (from 2.6 in FY2012 to 3.0 in FY2015, P < .001). Grant submissions, external funding, and teaching hours also increased per faculty but did not reach statistical significance. An important next step will be to incorporate quality metrics into the compensation plan, without affecting costs or throughput.


Concurrent immune-mediated haemolytic anaemia and severe thrombocytopenia in 21 dogs.
The medical records of 21 dogs with concurrent immune-mediated haemolytic anaemia (imha) and severe thrombocytopenia (defined as an automated platelet count of less than 50x10(9)/l, confirmed by the examination of a blood smear) were reviewed. Their mean (sd) age was 5.8 (2.5) years. When compared with the 24,759 dogs in the hospital population for the same period Airedale terriers and dobermanns appeared to be over-represented with odds ratios of 22.5 (95 per cent confidence interval [ci] 5.2 to 97.9) and 7.6 (95 per cent ci 1.8 to 32.7) respectively. The median duration of the dogs' clinical signs was seven days, with a range from one to 17 days. Eleven of the dogs had a history of a tendency to bleed, and 15 had evidence of bleeding when examined. Twenty of the 21 dogs had been treated with glucocorticoids, nine with vincristine, and seven with azathioprine. Their median stay in hospital was four days, with a range from one to 17 days. The median period for which they survived after admission to hospital was five days, with a range from one to 558 days, and 16 of the 21 dogs had died or been euthanased within 30 days of their admission.


Analysis of the endoplasmic reticular Ca2+ requirement for alpha1-antitrypsin processing and transport competence.
Depletion of Ca2+ sequestered within the endoplasmic reticulum (ER) of HepG2 hepatoma cells results in the luminal accumulation of immature alpha1-antitrypsin possessing Man8-9 GlcNAc2 oligosaccharide side chains. This study explores the basis for this arrest and describes consequent alterations in the size and rate of secretion of the complex endoglycosidase H-resistant form of the protein. Inhibition of glucosidase I and II with castanospermine or alpha-1,2-mannosidase with 1-deoxymannojirimycin produced altered ER processing intermediates that were rapidly secreted. Subsequent mobilization of ER Ca2+ stores resulted in the appearance and retention of slightly larger related forms of these intermediates. Retention of glycosylated intermediates was not ascribable to an association with alpha1,2-mannosidase or lectin-like chaperones, the intermediates were not degraded and all evidence of ER retention or size alterations produced by Ca2+ depletion was quickly reversed by Ca2+ restoration. Cells that were Ca2+ depleted for 2 h slowly secreted an abnormal slightly smaller complex oligosaccharide form of alpha1-antitrypsin at approximately the same rate as the non-glycosylated protein generated by treatment with tunicamycin. The hypothesis that Ca2+ affects the folding and ER transport competence of glycosylated forms of alpha1-antitrypsin is discussed.


Child food insecurity increases risks posed by household food insecurity to young children's health.
The US Food Security Scale (USFSS) measures household and child food insecurity (CFI) separately. Our goal was to determine whether CFI increases risks posed by household food insecurity (HFI) to child health and whether the Food Stamp Program (FSP) modifies these effects. From 1998 to 2004, 17,158 caregivers of children ages 36 mo were interviewed in six urban medical centers. Interviews included demographics, the USFSS, child health status, and hospitalization history. Ten percent reported HFI, 12% HFI and CFI (H&CFI). Compared with food-secure children, those with HFI had significantly greater adjusted odds of fair/poor health and being hospitalized since birth, and those with H&CFI had even greater adverse effects. Participation in the FSP modified the effects of FI on child health status and hospitalizations, reducing, but not eliminating, them. Children in FSP-participating households that were HFI had lower adjusted odds of fair/poor health [1.37 (95% CI, 1.06-1.77)] than children in similar non-FSP households [1.61 (95% CI, 1.31-1.98)]. Children in FSP-participating households that were H&CFI also had lower adjusted odds of fair/poor health [1.72 (95% CI, 1.34-2.21)] than in similar non-FSP households [2.14 (95% CI, 1.81-2.54)]. HFI is positively associated with fair/poor health and hospitalizations in young children. With H&CFI, odds of fair/poor health and hospitalizations are even greater. Participation in FSP reduces, but does not eliminate, effects of FI on fair/poor health.


Exploring the effects of icon characteristics on user performance: the role of icon concreteness, complexity, and distinctiveness.
Because icons, signs, and symbols are now widely used to communicate information, it is essential for system designers to know what makes them easy to use and interpret. The authors report a series of studies that examine characteristics considered central to icon usability. After quantifying the properties of icon concreteness, complexity, and discriminability, the authors assessed each property's effects on user performance when user experience, task demands, and presentation context were systematically varied. Findings indicated that the effects of icon concreteness were primarily associated with the initial grasp of meaning, whereas complexity effects were found to persist longer and to be associated with search efficacy. The effects of icon distinctiveness were complex, but distinctiveness was enhanced by using both semantic and visual contrasts. The implications of these findings for interface design are discussed.


Effects of shaker-1 mutations on myosin-VIIa protein and mRNA expression.
Numerous mammalian diseases have been found to be due to mutations in components of the actin cytoskeleton. Recently, mutations in the gene for an unconventional myosin, myosin-VIIa, were found to be the basis for the deafness and vestibular dysfunction observed in shaker-1 (sh1) mice and for a human deafness-blindness syndrome, Usher syndrome type 1B. Seven alleles of sh1 mice were analyzed to assess the affects of different myosin-VIIa mutations on both gene expression and tissue function. Myosin-VIIa is expressed in the inner ear and the retina, as well as the kidney, lung, and testis. Northern blot analysis indicated that myosin-VIIa mRNA expression, size, and stability were unaffected in the seven sh1 alleles. Immunoblot analysis showed that all seven alleles expressed some full-length myosin-VIIa protein. The range of expression, however, ran from sh1 [original], which expressed wild-type levels of protein, to two strains, sh1(4494SB) and sh1(4626SB), which expressed less than 1% of the normal level of myosin-VIIa protein. For the three alleles of sh1 that have been characterized and that have mutations in the motor domain, sh1 [original], sh1(816SB) and sh1(6J), the level of protein expression observed in these sh1 alleles correlated well with the predicted effects of the mutations on motor function. No change in retinal or testicular structure was observed at the light microscopic level during the life span of the seven sh1 alleles. Myosin-VIIa protein, when detectable, was observed to locate properly in the sh1 mice. On the basis of these results, we propose that the mutations in myosin-VIIa in the sh1 alleles leads to both motor dysfunction and to a protein destabilization phenotype.


Femoral bone loss in revision total hip arthroplasty: evaluation and management.
Primary total hip arthroplasty (THA) is one of the most effective procedures for managing end-stage hip arthritis. The burden of revision THA procedures is expected to increase along with the rise in number of primary THAs. The major indications for revision THA include instability, aseptic loosening, infection, osteolysis, wear-related complications, periprosthetic fracture, component malposition, and catastrophic implant fracture. Each of these conditions may be associated with mild or advanced bone loss. Careful patient evaluation and bone loss classification guide preoperative planning and overall patient care. Historically, uncemented fixation has provided the best results, but cemented fixation is required in some cases.


Experiential knowledge in mental health services: Analysing the enactment of expertise in peer support.
The shift towards recovery-oriented mental health care has led to the extensive growth of peer support in contemporary service delivery. When enacting peer support, peer workers (PWs) use their lived experiences of mental illness to provide support to individuals experiencing mental health difficulties. While PWs are increasingly an integrated part of mental health services, the way in which peer support unfolds in everyday practices remains understudied. Drawing on ethnographic fieldwork from Danish mental health centres, this paper investigates how peer workers and users enact experiential knowledge and expertise to support one another. Theoretically, this paper draws on a micro-sociological approach that comprehends expertise as an interactional accomplishment enacted within institutional arrangements. First, the analysis shows how PWs and users develop affective relations based on shared illness experiences that enable the enactment of expertise. Second, it demonstrates how PWs and users engage in these relations by exchanging sympathy and knowledge according to different situational demands. Third, it shows how experiences of relational limitations make service users contest the value of experiential knowledge and PWs' position as valid experts. Centrally, this paper contributes to a general discussion of expertise and the implications of bringing lived experiences into mental health services.


The Legal, Ethical, and Scientific Considerations for Returning Explanted Orthopaedic Hardware to the Patient.
Orthopaedic hardware explantation is a multifaceted topic with complex legal, ethical, and scientific aspects that require thorough exploration. Issues of device ownership, explant-induced disease propagation, and potential device resale pose legal risks to providers and health-care institutions. Ethically, implant removal highlights the potential that performing procedures at the request of the patient will incentivize patient compliance and strengthen the patient-surgeon relationship. However, the return of explanted hardware to patients could hinder scientific study and innovation, ultimately limiting advancement in risk reduction and patient outcomes. Continued research into these topics remains paramount to ensure that clinicians and institutions deliver optimal patient care while abiding with legal and ethical imperatives. This article addresses the legal, ethical, and scientific issues that are pertinent to returning an explanted orthopaedic implant to the patient and the potential ramifications of such practice.


Molecular pathways: not a simple tube--the many functions of blood vessels.
Although the ability of blood vessels to carry fluid and cells through neoplastic tissue is clearly important, other functions of vascular elements that drive tumor growth and progression are increasingly being recognized. Vessels can provide physical support and help regulate the stromal microenvironment within tumors, form niches for tumor-associated stem cells, serve as avenues for local tumor spread, and promote relative immune privilege. Understanding the molecular drivers of these phenotypes will be critical if we are to therapeutically target their protumorigenic effects. The potential for neoplastic cells to transdifferentiate into vascular and perivascular elements also needs to be better understood, as it has the potential to complicate such therapies. In this review, we provide a brief overview of these less conventional vascular functions in tumors.


School and work absenteeism due to menstruation in three West African countries: findings from PMA2020 surveys.
Reports of school and work absences due to unmet menstrual needs have prompted increased attention to menstruation in policy and practice. However, there appear to be few quantitative studies reported in published literature capturing the prevalence of this hypothesised absenteeism. This study undertook secondary analysis of nationally representative Performance Monitoring and Accountability 2020 (PMA2020) data from Burkina Faso and Nigeria, and city-representative data from Niamey, Niger to determine the extent of women's and girls' self-reported absence from school and work due to menstruation. Among women and adolescent girls aged 15-49 years who had worked outside the household in the past month in Burkina Faso (n = 998), Niger (n = 212) and Nigeria (n = 3638), 19%, 11% and 17%, respectively, reported missing work due to menstruation. Among those aged 15-24 years who attended school in the past year in Burkina Faso (n = 461), Niger (n = 213) and Nigeria (n = 1574), 17%, 15% and 23% reported missing school in the past year due to menstruation. Findings support the assertion that menstruation is a source of absenteeism in West Africa and indicate that greater attention from research, practice, and policy is needed. In presenting this data we also reflect critically on the performance of questions regarding menstrual-related absenteeism in national monitoring surveys. Future monitoring efforts should consider the interpretability of similar survey data when many respondents did not attend any school or work and were ineligible to answer questions regarding absenteeism. Further, without additional research identifying the reasons for absenteeism, findings from similar survey questions may be difficult to interpret with relevance for policy decision making.


AbCD: arbitrary coverage design for sequencing-based genetic studies.
Recent advances in sequencing technologies have revolutionized genetic studies. Although high-coverage sequencing can uncover most variants present in the sequenced sample, low-coverage sequencing is appealing for its cost effectiveness. Here, we present AbCD (arbitrary coverage design) to aid the design of sequencing-based studies. AbCD is a user-friendly interface providing pre-estimated effective sample sizes, specific to each minor allele frequency category, for designs with arbitrary coverage (0.5-30×) and sample size (20-10 000), and for four major ethnic groups (Europeans, Africans, Asians and African Americans). In addition, we also present two software tools: ShotGun and DesignPlanner, which were used to generate the estimates behind AbCD. ShotGun is a flexible short-read simulator for arbitrary user-specified read length and average depth, allowing cycle-specific sequencing error rates and realistic read depth distributions. DesignPlanner is a full pipeline that uses ShotGun to generate sequence data and performs initial SNP discovery, uses our previously presented linkage disequilibrium-aware method to call genotypes, and, finally, provides minor allele frequency-specific effective sample sizes. ShotGun plus DesignPlanner can accommodate effective sample size estimate for any combination of high-depth and low-depth data (for example, whole-genome low-depth plus exonic high-depth) or combination of sequence and genotype data [for example, whole-exome sequencing plus genotyping from existing Genomewide Association Study (GWAS)].


Distance from Healthcare Facilities Is Associated with Increased Morbidity of Acute Infection in Pediatric Patients in Matiari, Pakistan.
The relationship between environmental factors and child health is not well understood in rural Pakistan. This study characterized the environmental factors related to the morbidity of acute respiratory infections (ARIs), diarrhea, and growth using geographical information systems (GIS) technology. Anthropometric, address and disease prevalence data were collected through the SEEM (Study of Environmental Enteropathy and Malnutrition) study in Matiari, Pakistan. Publicly available map data were used to compile coordinates of healthcare facilities. A Pearson correlation coefficient (r) was used to calculate the correlation between distance from healthcare facilities and participant growth and morbidity. Other continuous variables influencing these outcomes were analyzed using a random forest regression model. In this study of 416 children, we found that participants living closer to secondary hospitals had a lower prevalence of ARI (r = 0.154, p < 0.010) and diarrhea (r = 0.228, p < 0.001) as well as participants living closer to Maternal Health Centers (MHCs): ARI (r = 0.185, p < 0.002) and diarrhea (r = 0.223, p < 0.001) compared to those living near primary facilities. Our random forest model showed that distance has high variable importance in the context of disease prevalence. Our results indicated that participants closer to more basic healthcare facilities reported a higher prevalence of both diarrhea and ARI than those near more urban facilities, highlighting potential public policy gaps in ameliorating rural health.


Effects of long-term restricted feeding on motor activity rhythm in the rat.
The motor activity circadian rhythm of the rat is driven by at least two different pacemakers, one entrained by light-dark cycles and the other by periodic food access. The interaction between these two pacemakers generates the overt rhythm in many variables in the rat. In this paper we study the effects of restricted feeding (RF) for > 300 days on the motor activity of two groups of eight rats each (4 males and 4 females) that were kept under different light patterns. The first group was kept under dim red light, and the second group was kept initially for 70 days under bright light and afterward under dim red light. Rats had access to food for only 2 h/day. Results show that strong alterations in the motor activity pattern, such as relative coordination, bouncing, and several cases of entrainment, are shown in the first group. When these animals return to ad libitum feeding conditions the presence of the food component is clear, in some cases for > 20 days. In contrast, the rats that were previously subjected to bright light did not entrain to RF. In this group, there was a masking effect when lights were on, but a free-running component appeared when lights were off. The endogenous period (tau) of this component was not modified during the course of the experiment. After RF these rats showed a longer tau than the former group.(ABSTRACT TRUNCATED AT 250 WORDS)


Real-time imaging of photosynthetic oxygen evolution from spinach using LSI-based biosensor.
The light-driven splitting of water to oxygen (O2) is catalyzed by a protein-bound tetra-manganese penta-oxygen calcium (Mn4O5Ca) cluster in Photosystem II. In the current study, we used a large-scale integration (LSI)-based amperometric sensor array system, designated Bio-LSI, to perform two-dimensional imaging of light-induced O2 evolution from spinach leaves. The employed Bio-LSI chip consists of 400 sensor electrodes with a pitch of 250 μm for fast electrochemical imaging. Spinach leaves were illuminated to varying intensities of white light (400-700 nm) which induced oxygen evolution and subsequent electrochemical images were collected using the Bio-LSI chip. Bio-LSI images clearly showed the dose-dependent effects of the light-induced oxygen release from spinach leaves which was then significantly suppressed in the presence of urea-type herbicide 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Our results clearly suggest that light-induced oxygen evolution can be monitored using the chip and suggesting that the Bio-LSI is a promising tool for real-time imaging. To the best of our knowledge, this report is the first to describe electrochemical imaging of light-induced O2 evolution using LSI-based amperometric sensors in plants.


Diagnosis of prostate cancer: comparison of serum prostate specific antigen, digital rectal examination and transrectal ultrasonography.
While prostate specific antigen (PSA) is useful as a tumor marker for monitoring patients with prostate cancer after definitive therapy, limitations have been noted when it is used for early detection of prostate cancer. We reviewed the charts of 121 patients who had undergone prostate needle biopsies, documented digital rectal examination (DRE) and serum PSA determination before biopsy from January 1993 to October 1994. Indications for biopsy included abnormal DRE. PSA level greater than 4.0 ng/ml or abnormal lesions on transrectal ultrasonography (TRUS). Seventeen patients (14%) had stage A carcinoma with normal DRE and PSA levels from 0.1 to 34.9 ng/ml (mean 9.0 ng/ml). Four patients (3%) had stage B carcinoma with an average PSA level of 32.3 ng/ml and less than one lobe indurated on DRE. Six patients (5%) had stage C carcinoma and had an average PSA level of 48.5 ng/ml and less than one lobe indurated on DRE. Ninety-four (78%) patients had stage D carcinoma with an average PSA level of 120 ng/ml and more than one lobe indurated on DRE. While hypoechoic sectors were more than twice as likely as isoechoic sectors of the prostate to contain malignancy on biopsy, nearly 20% of cancers were found in isoechoic sectors. Serum PSA is the most accurate of the three diagnostic tests evaluated. The addition of DRE or TRUS improves the detection rate of prostate cancer over PSA alone.


Intergenerational environmental effects: functional signals in offspring transcriptomes and metabolomes after parental jasmonic acid treatment in apomictic dandelion.
Parental environments can influence offspring traits. However, the magnitude of the impact of parental environments on offspring molecular phenotypes is poorly understood. Here, we test the direct effects and intergenerational effects of jasmonic acid (JA) treatment, which is involved in herbivory-induced defense signaling, on transcriptomes and metabolomes in apomictic common dandelion (Taraxacum officinale). In a full factorial crossed design with parental and offspring JA and control treatments, we performed leaf RNA-seq gene expression analysis, LC-MS metabolomics and total phenolics assays in offspring plants. Expression analysis, leveraged by a de novo assembled transcriptome, revealed an induced response to JA exposure that is consistent with known JA effects. The intergenerational effect of treatment was considerable: 307 of 858 detected JA-responsive transcripts were affected by parental JA treatment. In terms of the numbers of metabolites affected, the magnitude of the chemical response to parental JA exposure was c. 10% of the direct JA treatment response. Transcriptome and metabolome analyses both identified the phosphatidylinositol signaling pathway as a target of intergenerational JA effects. Our results highlight that parental environments can have substantial effects in offspring generations. Transcriptome and metabolome assays provide a basis for zooming in on the potential mechanisms of inherited JA effects.


Critical review of host specificity and its coevolutionary implications in the fig/fig-wasp mutualism.
Figs (Ficus spp., Moraceae) and their pollinating wasps (Agaonidae, Chalcidoidea) constitute perhaps the most tightly integrated pollination mutualism that is known. Figs are characterized by extraordinarily high global and local species diversity. It has been proposed that the diversification of this mutualism has occurred through strict-sense coadaptation and cospeciation between pairs of fig and wasp species that are associated in highly specific one-to-one relationships. However, existing studies cast doubt on the generality of this proposition. Here, we review our current knowledge of the evolutionary history of the fig/fig-wasp mutualism. We critically examine the idea that codivergence between figs and their pollinators has been dominated by strict-sense cospeciation. We present phylogenetic and population genetic data from neotropical fig and fig wasp species that suggest that a more accurate model for diversification in this mutualism is that of groups of genetically well defined wasp species coevolving with genetically less well defined (frequently hybridizing) groups of figs. Last, we use our results to assess previously proposed hypotheses on models of speciation in this mutualism.


An improved procedure for the generation of recombinant single-chain Fv antibody fragments reacting with human CD13 on intact cells.
A procedure was developed to generate recombinant single chain Fv (scFv) antibody fragments reacting with the extracellular domain of human cell surface antigen CD13 (hCD13; aminopeptidase N) on intact cells. Membrane fractions prepared from a stably transfected hCD13-positive murine NIH/3T3 cell line were used to immunize BALB/c mice, with the intention that hCD13 would be the major immunogenic molecule recognized by the immune system. Spleen RNA from the immunized mice served to generate a combinatorial scFv phage display library. The library was adsorbed against non-transfected NIH/3T3 or Sf21 insect cells to eliminate nonrelevant binders. The supernatant was then used for panning with either hCD13-transfected Sf21 insect cells or a hCD13-expressing human leukemia-derived cell line. Therefore, the key concepts of the procedure were the presentation of hCD13 as the sole human antigen on murine NIH/3T3 cells and a screening strategy where hCD13 was the major common antigen of the material used for immunization and panning. Two different hCD13-reactive phages were isolated and the soluble scFvs were expressed in E. coli and purified. The two scFvs, anti-hCD13-1 and anti-hCD13-3, differed at four amino acid positions in their V(H) regions and both had high affinities for hCD13 as determined by surface plasmon resonance (K(D)=7 and 33x10(-10) M, respectively). Both efficiently recognized hCD13 on intact cells. Therefore, the procedure allowed the production of high affinity scFvs reacting with a desired antigen in its native conformation without requiring extensive purification of the antigen and should be useful for the preparation of scFvs against other conformation-sensitive cell-surface antigens.


Optical coherence tomography angiography characterisation of Best disease and associated choroidal neovascularisation.
To characterise the vasculature of the retina in patients with Best vitelliform dystrophy, including those with choroidal neovascularisation (CNV), using optical coherence tomography angiography (OCTA) and correlate with fluorescein angiography (FA). This prospective observational study included 19 eyes of 10 patients with Best disease. Using OCTA, all layers of retina were qualitatively characterised for each eye. Patients with CNV also underwent FA, and areas of CNV were measured by OCTA and FA and correlated. Retinal characteristics revealed 14 (74%) eyes with abnormal foveal avascular zone (FAZ) in the superficial layer, 19 eyes (100%) had an abnormal FAZ in deep layers, 11 (58%) eyes had a hyper-reflective centre in the superficial layer, 18 (95%) had patchy vascularity loss in the deep layer, 17 (89%) eyes had hyporeflective centre in the choriocapillary (CC) layer and 12 (63%) of those eyes had hyper-reflective material within the hyporeflective centre. Also, notably 6 (86%) CNV eyes had a "halo" or a hypolucent area surrounded in the CNV complex in the outer retinal layer. CNV patterns resembled dense net, loose net, mixed and a new found pattern of a ring shape. CNV measurements revealed an average area of 1.66±1.18mm2 using OCTA and an average area of 0.88±0.76mm2 using FA (p=0.15). OCTA reveals that eyes with Best disease have abnormal FAZ, patchy vascularity loss in the superficial and deep layers of the retina and capillary dropout with a hyporeflective centre in CC layer. Further, OCTA is superior to FA in measuring CNV.


Reeling in the damages: Harmful algal blooms' impact on Lake Erie's recreational fishing industry.
Lake Erie is one of the most valuable natural resources in the United States, providing billions of dollars in benefits each year to recreationalists, homeowners and local governments. The ecosystem services provided by Lake Erie, however, are under threat due to harmful algal blooms. This paper provides recreational damage estimates using spatially and temporally varying algae measures and monthly fishing permit sales collected between 2011 and 2014. Results indicate that fishing license sales drop between 10% and 13% when algal conditions surpass the World Health's Organization's moderate health risk advisory threshold of 20,000 cyanobacteria cells/mL. For Lake Erie adjacent counties experiencing a large, summer-long algal bloom, this would result in approximately 3600 fewer fishing licenses issued and approximately $2.25 million to $5.58 million in lost fishing expenditures. Our results show a discrete jump in reduced angling activity upon crossing this threshold, with limited additional impacts associated with more severe algal blooms. This suggests that policies aimed at eliminating, rather than mitigating, algal levels are most beneficial to the Ohio angling industry.


Pressure-induced endothelial Ca(2+) oscillations in lung capillaries.
Endothelial second messenger responses may contribute to the pathology of high vascular pressure but remain poorly understood because of the lack of direct in situ quantification. In lung venular capillaries, we determined endothelial cytosolic Ca(2+) concentration [Ca(2+)](i) by the fura 2 ratioing method. Pressure elevation increased mean endothelial [Ca(2+)](i) by Ca(2+) influx through gadolinium-inhibitable channels and amplified [Ca(2+)](i) oscillations by Ca(2+) release from intracellular stores. Endothelial [Ca(2+)](i) transients were induced by pressure elevations of as little as 5 cmH(2)O and increased linearly with higher pressures. Heptanol inhibition of [Ca(2+)](i) oscillations in a subset of endothelial cells indicated that oscillations originated from pacemaker endothelial cells and were propagated to adjacent nonpacemaker cells by gap junctional communication. Our findings indicate the presence of a sensitive, active endothelial response to pressure challenge in lung venular capillaries that may be relevant in the pathogenesis of pressure-induced lung microvascular injury.


Expression of integrin-alphaE by mucosal mast cells in the intestinal epithelium and its absence in nematode-infected mice lacking the transforming growth factor-beta1-activating integrin alphavbeta6.
Peak intestinal mucosal mast cell (MMC) recruitment coincides with expulsion of Trichinella spiralis, at a time when the majority of the MMCs are located within the epithelium in BALB/c mice. Although expression of integrin-alpha(E)beta(7) by MMCs has not been formally demonstrated, it has been proposed as a potential mechanism to account for the predominantly intraepithelial location of MMCs during nematode infection. Co-expression of integrin-alpha(E)beta(7) and the MMC chymase mouse mast cell protease-1, by mouse bone marrow-derived mast cells, is strictly regulated by transforming growth factor (TGF)-beta(1). However, TGF-beta(1) is secreted as part of a latent complex in vivo and subsequent extracellular modification is required to render it biologically active. We now show, for the first time, that intraepithelial MMCs express integrin-alpha(E)beta(7) in Trichinella-infected BALB/c and S129 mice. In S129 mice that lack the gene for the integrin-beta(6) subunit and, as consequence, do not express the epithelial integrin-alpha(v)beta(6), integrin-alpha(E) expression is virtually abolished and recruitment of MMCs into the intestinal epithelium is dramatically reduced despite significant overall augmentation of the MMC population. Because a major function of integrin-alpha(v)beta(6) is to activate latent TGF-beta(1,) these findings strongly support a role for TGF-beta(1) in both the recruitment and differentiation of murine MMCs during nematode infection.


Scottish survey of public place defibrillators.
Public place defibrillators can reduce delays to defibrillation but their cost-effectiveness has not been evaluated in randomised trials. In Scotland, unlike England, no health sector funding has been provided. Nonetheless, anecdotal evidence suggests they are increasing in number. A cross-sectional survey was conducted of all airports, shopping malls, leisure centres, and major train and bus stations to determine whether defibrillators had been purchased and by whom, the training and maintenance arrangements, and whether they had been discharged. Of the 183 eligible sites, 153 (84%) participated. 33 (22%) had at least one defibrillator. Those in airports and shopping malls were purchased privately. Those in leisure centres were bought by charities or local authorities. The majority (97%) provided training to existing staff, but 6 (18%) provided no training to new staff. Only 6 (18%) had a maintenance agreement and 8 (24%) a replacement policy. Only one site permitted public access. Defibrillators had been discharged in 10 (30%) sites. Of the 32 people shocked, 23 (72%) survived until the ambulance arrived. Despite absence of health sector funding, defibrillators are located in 22% of high footfall public places. Those purchasing defibrillators need to ensure adequate maintenance, replacement and training arrangements.


The ocean noise coherence matrix and its rank.
An expression for the cross-spectral density matrix of ocean noise naturally separates into a Toeplitz part and a Hankel part [Harrison (2017). J. Acoust. Soc. Am. 141, 2812-2820]. The Toeplitz part is shown to be substantially rank-deficient for all practical acoustic cases, which has implications for adaptive beam forming. The influence of the Hankel part on passive fathometry is investigated, and its effect on adaptive beam forming is shown to be weak or negligible. Numerical demonstrations of these findings including beam patterns and eigenvalue spectra derived via circulant matrices are given based on a simple half-space with a Rayleigh reflection coefficient. Two sets of experimental data are revisited in this context, deriving eigenvalue spectra, beam patterns, and passive fathometry impulse responses with conventional and adaptive processing and differing amounts of averaging. The solution to a long-standing puzzle of processing inconsistency is suggested.


Auxin modulates the enhanced development of root hairs in Arabidopsis thaliana (L.) Heynh. under elevated CO(2).
Root hairs may play a critical role in nutrient acquisition of plants grown under elevated CO(2) . This study investigated how elevated CO(2) enhanced the development of root hairs in Arabidopsis thaliana (L.) Heynh. The plants under elevated CO(2) (800 µL L(-1)) had denser and longer root hairs, and more H-positioned cells in root epidermis than those under ambient CO(2) (350 µL L(-1)). The elevated CO(2) increased auxin production in roots. Under elevated CO(2) , application of either 1-naphthoxyacetic acid (1-NOA) or N-1-naphthylphthalamic acid (NPA) blocked the enhanced development of root hairs. The opposite was true when the plants under ambient CO(2) were treated with 1-naphthylacetic acid (NAA), an auxin analogue. Furthermore, the elevated CO(2) did not enhance the development of root hairs in auxin-response mutants, axr1-3, and auxin-transporter mutants, axr4-1, aux1-7 and pin1-1. Both elevated CO(2) and NAA application increased expressions of caprice, triptychon and rho-related protein from plants 2, and decreased expressions of werewolf, GLABRA2, GLABRA3 and the transparent testa glabra 1, genes related to root-hair development, while 1-NOA and NPA application had an opposite effect. Our study suggests that elevated CO(2) enhanced the development of root hairs in Arabidopsis via the well-characterized auxin signalling and transport that modulate the initiation of root hairs and the expression of its specific genes.


The peroxisomal SspA protein is redundant for purine utilization but essential for peroxisome localization in septal pores in Aspergillus nidulans.
In an in silico search for correlated gene loss with fungal peroxisomal uric acid oxidase (UOX), we identified PMP22-like proteins, some of which function as promiscuous channels in organellar membranes. To investigate whether PMP22 channels have a role in peroxisomal uric acid transport and catabolism, we functionally analyzed the closest homologue in Aspergillus nidulans, named SspA. We confirmed that SspA is a peroxisomal membrane protein that co-localizes significantly with PTS1-tagged mRFP, UOX or HexA, the latter considered a protein of Woronin bodies (WB), organelles originating from peroxisomes that dynamically plug septal pores in ascomycetes. Our results suggest that in A. nidulans, unlike some other ascomycetes, there is no strict protein segregation of peroxisomal and WB-specific proteins. Importantly, genetic deletion of sspA, but not of hexA, led to lack of peroxisomal localization at septal pores, suggesting that SspA is a key factor for septal pore functioning. Additionally, ΔsspA resulted in increased sensitivity to oxidative stress, apparently as a consequence of not only the inability to plug septal pores, but also a recorded reduction in peroxisome biogenesis. However, deleting sspA had no effect on uric acid or purine utilization, as we hypothesized, a result also in line with the observation that expression of SspA was not affected by regulatory mutants and conditions known to control purine catabolic enzymes. Our results are discussed within the framework of previous studies of SspA homologues in other fungi, as well as, the observed gene losses of PMP22 and peroxisomal uric acid oxidase.


The cape mendocino, california, earthquakes of april 1992: subduction at the triple junction.
The 25 April 1992 magnitude 7.1 Cape Mendocino thrust earthquake demonstrated that the North America-Gorda plate boundary is seismogenic and illustrated hazards that could result from much larger earthquakes forecast for the Cascadia region. The shock occurred just north of the Mendocino Triple Junction and caused strong ground motion and moderate damage in the immediate area. Rupture initiated onshore at a depth of 10.5 kilometers and propagated up-dip and seaward. Slip on steep faults in the Gorda plate generated two magnitude 6.6 aftershocks on 26 April. The main shock did not produce surface rupture on land but caused coastal uplift and a tsunami. The emerging picture of seismicity and faulting at the triple junction suggests that the region is likely to continue experiencing significant seismicity.