Vaping industry participation standards in health organizations: an exploratory policy content analysis.
The vaping industry has been found to employ similar tactics to tobacco industry actors to seek credibility and distort the scientific evidence base around the health harms of nicotine vaping products. As vaping industry interests undermine vaping control efforts, safeguards are necessary to protect against this influence. We aimed to examine health organizations' policies on vaping industry participation in their activities in Australia. A descriptive approach integrating policy analysis and key informant surveys was used to obtain vaping industry participation information from health research stakeholders. Descriptive statistics on organization type, policy document type, policy document industry focus (tobacco or vaping) and respondent role and responsibility were collected. We used framework analysis to identify themes describing organizational allowances, constraints, and rationale for vaping industry research participation. Relevant health organizations were identified within Australia for policy searching (n = 156), which identified 47 unique policy documents. After contacting 267 key stakeholders from eligible organizations, 31 survey responses were analysed. Research organizations and universities were highly represented in both the policy and survey data. Most health research stakeholders recognized that vaping industry interests counteract public health priorities and opposed vaping industry participation. However, many organizations lacked clear, vaping industry-specific participation policies. To protect the integrity of the emerging evidence base around vaping harms which inform vaping policy, health organizations require strong, comprehensive policies to resist vaping industry participation in research.


Diagnostic aspects and syndromal associations of short trachea with bronchial intubation.
Conditions with disproportionately short trachea, with a reduced number of tracheal cartilage rings and a high level of tracheal bifurcation, have been reported. We have seen accidental bronchial intubation in nine patients with short trachea. This risk can be reduced by recognition of conditions associated with short trachea, by awareness that methods for calculating endotracheal tube length from body length can overpredict tube length for patients with short trachea, and when feasible, by use of preintubation chest roentgenograms showing air bronchograms to establish the thoracic level of tracheal bifurcation. Twelve patients with short trachea, four with bronchial intubation, and six conditions not previously associated with short trachea, are reported. Three of the patients also had laryngeal hypoplasia.


The response of the macaque tracheobronchial epithelium to acute ozone injury. A quantitative ultrastructural and autoradiographic study.
The tracheal epithelium of a variety of laboratory species is widely used as a model system in studies of epithelial biology and respiratory carcinogenesis. The purpose of this study was to evaluate the response of the tracheal epithelium to cytotoxic injury in a primate species that may have an epithelium more representative of that in man than smaller laboratory species. This study evaluated changes in the light-microscopic, surface, and ultrastructural appearance of the tracheobronchial epithelium of bonnet monkeys exposed for 3 or 7 days to 0.64 ppm ozone. Population densities, epithelial volumetric densities, and thymidine labeling indexes were determined for cells from posterior membranous and anterior cartilaginous trachea and mainstem bronchus. Ozone-induced epithelial changes were characterized by decreased numbers of ciliated cells, loss of cilia, and necrosis of ciliated cells. There were alterations in mucous (goblet) cell granules. There was an increase in extracellular space and focal epithelial stratification that was associated with increased numbers of small mucous granule cells and the presence of an epithelial cell type not seen in control animals (intermediate cells). There was an increase in cytoplasmic filaments and desmosomal attachments in basal cells, small mucous granule cells, and intermediate cells. Regional differences in lesion distribution were demonstrated by scanning electron microscopy. Longitudinal streaks of ciliary loss were evident in posterior membranous trachea, but ciliary loss in the ventral trachea was most prominent over the posterior border of the cartilaginous rings. The thymidine labeling index and numbers of necrotic ciliated cells were greater after 3 days than after 7 days of continuous exposure. Foci of stratification were often associated with increased numbers of labeled nuclei in the suprabasal region of the epithelium. The results of this study suggest that small mucous granule cells and intermediate cells are important participants in the repair of chemically injured airway epithelium; stratification and increased amounts of cytoplasmic filament bundles and desmosomal attachments, rather than being evidence of squamous metaplasia or dysplastic change, might be stereotypic responses of airway epithelium to injury; and the ciliated cell population becomes less susceptible to ozone-induced necrosis with continuing exposure.


Cholestasis: A Prospective Study of Perinatal Outcomes and Time to Symptom Improvement.
Although intrahepatic cholestasis of pregnancy (ICP) remains poorly understood, there are several perinatal complications associated with this condition. This study aimed to examine perinatal outcomes of women with ICP, evaluate outcomes according to severity of disease, and monitor time to symptom improvement following diagnosis. It involves a prospective, observational study of women with ICP at a single institution. Women with new-onset pruritus without rash were referred to a high-risk obstetrics clinic and evaluated with fasting total bile acids (TBA). Laboratory-confirmed ICP was defined as fasting TBA ≥10 µmol/L. Following diagnosis, a standardized protocol was utilized, including treatment with ursodeoxycholic acid (UDCA). Perinatal outcomes were compared amongst those with and without ICP, and to the general population. Women with ICP were further analyzed based on maximum TBA: 10 to 39, 40 to 99, and ≥100 µmol/L. A Kaplan-Meier survival curve was used to analyze time to symptom improvement. A total of 404 patients were evaluated and 212 (52%) were diagnosed with ICP. The mean gestational age at diagnosis was 34.1 ± 3.3 weeks. When comparing those with ICP to those not confirmed, and to the general population, there were no differences in age, parity, mode of delivery, preeclampsia, or stillbirth (p > 0.05). Preterm birth was significantly associated with ICP (p < 0.01). This relationship was significant across increasing severity of TBA (p < 0.01) and persisted when examining rates of spontaneous preterm birth (p < 0.01). All women with fasting TBA ≥40 µmol/L delivered preterm due to premature rupture of membranes or spontaneous labor. Time to symptom improvement after diagnosis was over 2 weeks on average; however, this time increased with worsening severity of disease. Despite treatment with UDCA, women with ICP are at increased risk for spontaneous preterm birth, and this risk significantly increased with severity of disease. Although not significant, a trend exists between increasing time to symptom improvement and worsening severity of disease. · Preterm birth is significantly increased in patients diagnosed with intrahepatic cholestasis of pregnancy.. · The risk of preterm birth in women with ICP increases across increasing strata of disease.. · Following initiation of treatment in patients with ICP, symptom improvement takes more than 2 weeks..


Cigarette smoke condensate inhibits collagen gel contraction and prostaglandin E2 production in human gingival fibroblasts.
Granulation tissue remodeling and myofibroblastic differentiation are critically important events during wound healing. Tobacco smoking has a detrimental effect in gingival tissue repair. However, studies evaluating the effects of cigarette smoke on these events are lacking. We used gingival fibroblasts cultured within free-floating and restrained collagen gels to simulate the initial and final steps of the granulation tissue phase during tissue repair. Collagen gel contraction was stimulated with serum or transforming growth factor-β1. Cigarette smoke condensate (CSC) was used to evaluate the effects of tobacco smoke on gel contraction. Protein levels of alpha-smooth muscle actin, β1 integrin, matrix metalloproteinase-3 and connective tissue growth factor were evaluated through Western blot. Prostaglandin E(2) (PGE(2)) levels were determined through ELISA. Actin organization was evaluated through confocal microscopy. CSC reduced collagen gel contraction induced by serum and transforming growth factor-β1 in restrained collagen gels. CSC also altered the development of actin stress fibers in fibroblasts cultured within restrained collagen gels. PGE(2) levels were strongly diminished by CSC in three-dimensional cell cultures. However, other proteins involved in granulation tissue remodeling and myofibroblastic differentiation such as alpha-smooth muscle actin, β1 integrin, matrix metalloproteinase-3 and connective tissue growth factor, were unmodified by CSC. CSC may alter the capacity of gingival fibroblasts to remodel and contract a collagen matrix. Inhibition of PGE(2) production and alterations of actin stress fibers in these cells may impair proper tissue maturation during wound healing in smokers.


The macroeconomic effects of adapting to high-end sea-level rise via protection and migration.
Climate change-induced sea level rise (SLR) is projected to be substantial, triggering human adaptation responses, including increasing protection and out-migration from coastlines. Yet, in macroeconomic assessments of SLR the latter option has been given little attention. We fill this gap by providing a global analysis of the macroeconomic effects of adaptation to SLR, including coastal migration, focusing on the higher end of SLR projections until 2050. We find that when adapting simultaneously via protection and coastal migration, macroeconomic costs can be lower than with protection alone. For some developing regions coastal migration is even less costly (in GDP) than protection. Additionally, we find that future macroeconomic costs are dominated by accumulated macroeconomic effects over time, rather than by future direct damages, implying the need for immediate adaptation. Finally, we demonstrate the importance of including autonomous adaptation in the reference scenario of economic assessment studies to avoid overestimation of adaptation benefits.


Functional diversification of the RING finger and other binuclear treble clef domains in prokaryotes and the early evolution of the ubiquitin system.
Recent studies point to a diverse assemblage of prokaryotic cognates of the eukaryotic ubiquitin (Ub) system. These systems span an entire spectrum, ranging from those catalyzing cofactor and amino acid biosynthesis, with only adenylating E1-like enzymes and ubiquitin-like proteins (Ubls), to those that are closer to eukaryotic systems by virtue of possessing E2 enzymes. Until recently E3 enzymes were unknown in such prokaryotic systems. Using contextual information from comparative genomics, we uncover a diverse group of RING finger E3s in prokaryotes that are likely to function with E1s, E2s, JAB domain peptidases and Ubls. These E1s, E2s and RING fingers suggest that features hitherto believed to be unique to eukaryotic versions of these proteins emerged progressively in such prokaryotic systems. These include the specific configuration of residues associated with oxyanion-hole formation in E2s and the C-terminal UFD in the E1 enzyme, which presents the E2 to its active site. Our study suggests for the first time that YukD-like Ubls might be conjugated by some of these systems in a manner similar to eukaryotic Ubls. We also show that prokaryotic RING fingers possess considerable functional diversity and that not all of them are involved in Ub-related functions. In eukaryotes, other than RING fingers, a number of distinct binuclear (chelating two Zn atoms) and mononuclear (chelating one zinc atom) treble clef domains are involved in Ub-related functions. Through detailed structural analysis we delineated the higher order relationships and interaction modes of binuclear treble clef domains. This indicated that the FYVE domain acquired the binuclear state independently of the other binuclear forms and that different treble clef domains have convergently acquired Ub-related functions independently of the RING finger. Among these, we uncover evidence for notable prokaryotic radiations of the ZF-UBP, B-box, AN1 and LIM clades of treble clef domains and present contextual evidence to support their role in functions unrelated to the Ub-system in prokaryotes. In particular, we show that bacterial ZF-UBP domains are part of a novel cyclic nucleotide-dependent redox signaling system, whereas prokaryotic B-box, AN1 and LIM domains have related functions as partners of diverse membrane-associated peptidases in processing proteins. This information, in conjunction with structural analysis, suggests that these treble clef domains might have been independently recruited to the eukaryotic Ub-system due to an ancient conserved mode of interaction with peptides.


Phase aberration correction using near-field signal redundancy. I. Principles [Ultrasound medical imaging].
The signal redundancy principle in the near field is analyzed quantitatively. It is found that common midpoint signals are not identical (or redundant) for echoes coming from arbitrary target distributions in the near field. A dynamic near-field correction is proposed to reduce the difference between common midpoint signals for echoes coming from the region of interest. When phase aberrations are present, it is shown that the dynamic correction can generally be done assuming no phase aberration, and the relative time-shift between common midpoint signals can be used to measure phase-aberration profiles. A phase-aberration correction algorithm based on that principle is proposed. In this algorithm, after common midpoint signals are collected they are dynamically corrected for near-field effects and cross-correlated with one another. In a related way, the phase errors are measured from peak positions of these cross-correlation functions. The phase-aberration profile across the array is derived from these measurements. The relationship between the errors in the derived phase aberration profile and the errors in the measured relative time-shift between common midpoint signals is derived. A method for treating the situation of different transmission and reception phase-aberration profiles is also proposed. This algorithm works for general target distributions, iteration is not required, and it can be used in other near-field, pulse-echo, imaging systems.


A global analysis of Y-chromosomal haplotype diversity for 23 STR loci.
In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.


Stallion fertility: a focus on the spermatozoon.
Stallion fertility is a vast subject, with a wide array of permutations that can impact reproductive performance in either positive or negative ways. This review is intended to address a mere segment of the male fertility issue, but the very essence of the male contribution to fertilisation, that of the spermatozoon. Spermatozoal ultrastructure and form-to-function are detailed and spermatozoal metabolism is discussed, with specific reference to distinctive characteristics of stallion spermatozoa. Lastly, methods for assessment of spermatozoal function are considered, with emphasis on spermatozoal motility, the acrosome reaction and spermatozoon-oocyte interactions. Closing comments address the need for development and standardisation of molecular-based assays for use with spermatozoa of stallions whose subfertility cannot be explained with conventional tests.


Protein trans-splicing in transgenic plant chloroplast: reconstruction of herbicide resistance from split genes.
Inteins are intervening protein sequences that undergo self-excision from a precursor protein with concomitant joining of the flanking sequences. Here, we demonstrate intein trans-splicing in Nicotiana tabacum chloroplasts by using the naturally split Ssp DnaE intein. Trans-splicing occurred whether both intein fragments were encoded in the chloroplast or were separated into the chloroplast and nuclear genomes. A biolistic approach was used to integrate two fusion genes, one encoding aminoglycoside-3-adenyltransferase (aadA) and the first 123 aa of the Ssp DnaE intein (In) and the other encoding 36 C-terminal amino acid residues of the Ssp DnaE intein (Ic) and soluble modified green fluorescent protein (smGFP) into N. tabacum plastids. Expression of these gene fragments in the chloroplast resulted in ligated aadA-smGFP due to In-Ic-mediated trans-splicing. Furthermore, an N-terminal portion of the herbicide resistance gene 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) containing a chloroplast localization signal fused to In (EPSPSn-In) was integrated into the nuclear DNA of N. tabacum by using Agrobacterium tumefaciens-mediated transformation. The remaining EPSPS gene fragment (EPSPSc) fused to Ic (Ic-EPSPSc) was integrated into the chloroplast genome by homologous recombination. Western blot analysis of cell extracts from these plants showed a full-length EPSPS, demonstrating that the EPSPSn-In gene product migrated to the chloroplast and underwent trans-splicing. Furthermore, these transgenic plants displayed improved resistance to the herbicide N-(phosphonomethyl)glycine (glyphosate) when compared with wild-type N. tabacum.


Managing large bone defects in children: a systematic review of the 'induced membrane technique'.
Thirty years after its description by Masquelet in 1986, this is the first systematic review aiming to critically evaluate the 'induced membrane technique' effectiveness in achieving bone union in children. Only six papers fulfilled our inclusion criteria (54 patients). The relatively small number of reported cases did not allow a formal meta-analysis. The tibia was the most involved bone. Most frequent aetiologies were congenital pseudoarthrosis and tumour resections. Although effective in achieving bone healing in ∼91% of the patients (bone defects ≤24 cm long), the induced membrane technique was associated with a high rate of complications (54% of patients). IV.


Bony changes of the glenoid as a consequence of shoulder instability.
Among 500 skeletons of mature individuals, 27 showed signs of shoulder instability as indicated by the presence of a glenoid rim avulsion fracture, a bony Bankart lesion, with an anterior or posterior Hill-Sachs defect. Twenty-two of these glenoid lesions were anterior, and five were posterior. This is a higher prevalence than reported in clinical studies. With few exceptions the pathologic changes in the bony glenoid were well circumscribed and not found in conjunction with diffuse arthritic changes. These findings do not support prophylactic shoulder stabilization to avoid the development of arthritic changes of a generalized and major degree.


Simultaneous differential pulse polarographic determination of cadmium, lead, and copper in milk and dairy products.
The contents of potentially toxic elements lead and cadmium and the essential element copper in various milk and dairy products consumed in Turkey were determined by differential pulse polarography (DPP), primarily to assess whether the intakes comply with recommended desired concentrations for essential and permissible levels for toxic elements. A simple and rapid DPP method has been developed for the simultaneous determination of cadmium, lead, and copper in samples. Using the differential pulse mode, half-wave peak potentials as E(1/2) were -0.58, -0.40, and -0.07 V for cadmium (Cd), lead (Pb), and copper (Cu), respectively. Marketed formulations of dairy products have been analyzed by calibration and standard addition methods. Recovery experiments were found to be quantitative. The linear domain ranges were 0.00-674.28 microg/L for Cd (R2 = 0.9999), 0.19-2.94 mg/L (p < 0.01) for Pb (R2 = 0.9997), and 0.41-133.46 microg/L for Cu (p < 0.01) (R2 = 0.9999). The studies have shown that the method is a rapid, reproducible, and accurate determination of these elements in milk and dairy products and can be used in the analysis of marketed formulations in the milk and dairy industry.


Redescription of Cystidicoloides fischeri based on specimens from piranhas in Brazil, and erection of a new genus (Nematoda: Cystidicolidae).
The cystidicolid nematode Cystidicoloides fischeri (Travassos, Artigas and Pereira, 1928) is redescribed from specimens collected from the stomach of the San Francisco piranha, Pygocentrus piraya (Cuvier), and the white piranha, Serrasalmus brandtii (Lütken) (both Characidae, Characiformes) (new host records), from the Três Marias Reservoir, Upper São Francisco River, Minas Gerais state, Brazil. The morphology of this type species of Cystidicoloides Skinker, 1931, studied with both light and scanning electron microscopy, is characterized by some taxonomically important, previously unreported features, such as the presence of a cephalic cuticular collarette, subdorsal and subventral cephalic spikes, cuticular tooth-like elevations inside the prostom, deirids, area rugosa, and details in the structure of the cephalic end. Heliconema izecksohni Fabio, 1982 is transferred to Cystidicoloides as C. izecksohni (Fabio, 1982) n. comb. Cystidicoloides uniseriata Valovaya and Valter, 1988 is considered a species inquirenda with uncertain generic appurtenance. The presence of subdorsal and subventral cephalic spikes and the collarette are characteristic of Cystidicoloides, comprising only species parasitizing Neotropical fishes. The species from salmonids in the Holarctic, hitherto reported mostly as Cystidicoloides ephemeridarum (Linstow, 1872), belongs to a different, newly erected genus, for which the name Salmonema n. gen. (type species S. ephemeridarum) is now proposed. Cystidicoloides prevosti (Choquette, 1951) is transferred to Salmonema as S. prevosti (Choquette, 1951) n. comb. Sterliadochona ssavini Skryabin, 1948 and Sterliadochona Skryabin, 1948 are considered as species inquirenda and a genus inquirendum, respectively. A key to species of Cystidicoloides is provided.


Clickable protein nanocapsules for targeted delivery of recombinant p53 protein.
Encapsulating anticancer protein therapeutics in nanocarriers is an attractive option to minimize active drug destruction, increase local accumulation at the disease site, and decrease side effects to other tissues. Tumor-specific ligands can further facilitate targeting the nanocarriers to tumor cells and reduce nonspecific cellular internalization. Rationally designed non-covalent protein nanocapsules incorporating copper-free "click chemistry" moieties, polyethylene glycol (PEG) units, redox-sensitive cross-linker, and tumor-specific targeting ligands were synthesized to selectively deliver intracellular protein therapeutics into tumor cells via receptor-mediated endocytosis. These nanocapsules can be conjugated to different targeting ligands of choice, such as anti-Her2 antibody single-chain variable fragment (scFv) and luteinizing hormone releasing hormone (LHRH) peptide, resulting in specific and efficient accumulation within tumor cells overexpressing corresponding receptors. LHRH-conjugated nanocapsules selectively delivered recombinant human tumor suppressor protein p53 and its tumor-selective supervariant into targeted tumor cells, which led to reactivation of p53-mediated apoptosis. Our results validate a general approach for targeted protein delivery into tumor cells using cellular-responsive nanocarriers, opening up new opportunities for the development of intracellular protein-based anticancer treatment.


Approach and avoidance tendencies in depression and anxiety disorders.
Anxiety is linked to increased avoidance and inhibition, whereas depression is linked to decreased approach and diminished behavioral activation. Although these notions are widely recognized, systematic investigation of approach-avoidance tendencies is lacking across these diagnostic groups. Participants (mean age = 45.6; 65.8% female) were subdivided in healthy controls (405), remitted patients (877) and currently anxious (217), depressed (154) or comorbid (154) patients. Automatic approach-avoidance tendencies in reaction to facial expression were assessed using the Approach-Avoidance-Task (AAT). Self-reported trait approach and avoidance tendencies were assessed using the BIS/BAS scale. Severity of psychopathology was assessed to examine dose-response relationships. We did not find any consistent associations of automatic approach-avoidance tendencies with psychiatric variables. In contrast, medium to large differences in BIS scores showed increased trait avoidance tendencies in all patient groups relative to healthy controls. Overall, it seems that increased trait avoidance, rather than decreased approach, is a characteristic of affective disorders. This holds for both depressed and anxious patients and more strongly so in severe and chronic patients. It underlines the importance to address trait avoidance tendencies in the treatment of affective disorders.


Selective substrate supply in the regulation of yeast de novo sphingolipid synthesis.
The heat stress response of Saccharomyces cerevisiae is characterized by transient cell cycle arrest, altered gene expression, degradation of nutrient permeases, trehalose accumulation, and translation initiation of heat shock proteins. Importantly heat stress also induces de novo sphingolipid synthesis upon which many of these subprograms of the heat stress response depend. Despite extensive data addressing the roles for sphingolipids in heat stress, the mechanism(s) by which heat induces sphingolipid synthesis remains unknown. This study was undertaken to determine the events and/or factors required for heat stress-induced sphingolipid synthesis. Data presented indicate that heat does not directly alter the in vitro activity of serine palmitoyltransferase (SPT), the enzyme responsible for initiating de novo sphingolipid synthesis. Moreover deletion of the small peptide Tsc3p, which is thought to maximize SPT activity, specifically reduced production of C(20) sphingolipid species by over 70% but did not significantly decrease overall sphingoid base production. In contrast, the fatty-acid synthase inhibitor cerulenin nearly completely blocked sphingoid base production after heat, indicating a requirement for endogenous fatty acids for heat-mediated sphingoid base synthesis. Consistent with this, genetic studies show that fatty acid import does not contribute to heat-induced de novo synthesis under normal conditions. Interestingly the absence of medium serine also ameliorated heat-induced sphingoid base production, indicating a requirement for exogenous serine for the response, and consistent with this finding, disruption of synthesis of endogenous serine did not affect heat-induced sphingolipid synthesis. Serine uptake assays indicated that heat increased serine uptake from medium by 100% during the first 10 min of heat stress. Moreover treatments that increase serine uptake in the absence of heat including acute medium acidification and glucose treatment also enhanced de novo sphingoid base synthesis equivalent to that induced by heat stress. These data agree with findings from mammalian systems that availability of substrates is a key determinant of flux through sphingolipid synthesis. Moreover data presented here indicate that SPT activity can be driven by several factors that increase serine uptake in the absence of heat. These findings may provide insights into the many systems in which de novo synthesis is increased in the absence of elevated in vitro SPT activity.


Elevated ratio of urinary metabolites of thromboxane and prostacyclin is associated with adverse cardiovascular events in ADAPT.
Results from prevention trials, including the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT), have fueled discussion about the cardiovascular (CV) risks associated with non-steroidal anti-inflammatory drugs (NSAIDs). We tested the hypotheses that (i) adverse CV events reported among ADAPT participants (aged 70 years and older) are associated with increased ratio of urine 11-dehydrothromboxane B(2) (Tx-M) to 2'3-donor-6-keto-PGF1 (PGI-M) attributable to NSAID treatments; (ii) coincident use of aspirin (ASA) would attenuate NSAID-induced changes in Tx-M/PGI-M ratio; and (iii) use of NSAIDs and/or ASA would not alter urine or plasma concentrations of F(2)-isoprostanes (IsoPs), in vivo biomarkers of free radical damage. We quantified urine Tx-M and PGI-M, and urine and plasma F(2)-IsoPs from 315 ADAPT participants using stable isotope dilution assays with gas chromatography/mass spectrometry, and analyzed these data by randomized drug assignment and self-report compliance as well as ASA use. Adverse CV events were significantly associated with higher urine Tx-M/PGI-M ratio, which seemed to derive mainly from lowered PGI-M. Participants taking ASA alone had reduced urine Tx-M/PGI-M compared to no ASA or NSAID; however, participants taking NSAIDs plus ASA did not have reduced urine Tx-M/PGI-M ratio compared to NSAIDs alone. Neither NSAID nor ASA use altered plasma or urine F(2)-IsoPs. These data suggest a possible mechanism for the increased risk of CV events reported in ADAPT participants assigned to NSAIDs, and suggest that the changes in the Tx-M/PGI-M ratio was not substantively mitigated by coincident use of ASA in individuals 70 years or older.


Modelling damped acoustic waves by a dissipation-preserving conformal symplectic method.
We propose a novel stable and efficient dissipation-preserving method for acoustic wave propagations in attenuating media with both correct phase and amplitude. Through introducing the conformal multi-symplectic structure, the intrinsic dissipation law and the conformal symplectic conservation law are revealed for the damped acoustic wave equation. The proposed algorithm is exactly designed to preserve a discrete version of the conformal symplectic conservation law. More specifically, two subsystems in conjunction with the original damped wave equation are derived. One is actually the conservative Hamiltonian wave equation and the other is a dissipative linear ordinary differential equation (ODE) system. Standard symplectic method is devoted to the conservative system, whereas the analytical solution is obtained for the ODE system. An explicit conformal symplectic scheme is constructed by concatenating these two parts of solutions by the Strang splitting technique. Stability analysis and convergence tests are given thereafter. A benchmark model in homogeneous media is presented to demonstrate the effectiveness and advantage of our method in suppressing numerical dispersion and preserving the energy dissipation. Further numerical tests show that our proposed method can efficiently capture the dissipation in heterogeneous media.


Detection of Foot-and-mouth Disease Virus RNA and Capsid Protein in Lymphoid Tissues of Convalescent Pigs Does Not Indicate Existence of a Carrier State.
A systematic study was performed to investigate the potential of pigs to establish and maintain persistent foot-and-mouth disease virus (FMDV) infection. Infectious virus could not be recovered from sera, oral, nasal or oropharyngeal fluids obtained after resolution of clinical infection with any of five FMDV strains within serotypes A, O and Asia-1. Furthermore, there was no isolation of live virus from tissue samples harvested at 28-100 days post-infection from convalescent pigs recovered from clinical or subclinical FMD. Despite lack of detection of infectious FMDV, there was a high prevalence of FMDV RNA detection in lymph nodes draining lesion sites harvested at 35 days post-infection, with the most frequent detection recorded in popliteal lymph nodes (positive detection in 88% of samples obtained from non-vaccinated pigs). Likewise, at 35 dpi, FMDV capsid antigen was localized within follicles of draining lymph nodes, but without concurrent detection of FMDV non-structural protein. There was a marked decline in the detection of FMDV RNA and antigen in tissue samples by 60 dpi, and no antigen or viral RNA could be detected in samples obtained at 100 dpi. The data presented herein provide the most extensive investigation of FMDV persistence in pigs. The overall conclusion is that domestic pigs are unlikely to be competent long-term carriers of infectious FMDV; however, transient persistence of FMDV protein and RNA in lymphoid tissues is common following clinical or subclinical infection.


Non-aggregated Aβ25-35 Upregulates Primary Astrocyte Proliferation In Vitro.
Amyloid beta (Aβ) is a peptide cleaved from amyloid precursor protein that contributes to the formation of senile plaques in Alzheimer's disease (AD). The relationship between Aβ and astrocyte proliferation in AD remains controversial. Despite pathological findings of increased astrocytic mitosis in AD brains, in vitro studies show an inhibitory effect of Aβ on astrocyte proliferation. In this study, we determined the effect of an active fragment of Aβ (Aβ25-35) on the cell cycle progression of primary rat astrocytes. We found that Aβ25-35 (0.3-1.0 μg/ml) enhanced astrocyte proliferation in vitro in a time- and concentration-dependent manner. Increased DNA synthesis by Aβ25-35 was observed during the S phase of the astrocyte cell cycle, as indicated by proliferation kinetics and bromodeoxyuridine immunocytochemical staining. Aggregation of Aβ25-35 abolished the upregulatory effect of Aβ on astrocyte proliferation. Further examination indicated that Aβ25-35 affected astrocyte proliferation during early or mid-G1 phase but had no effect on DNA synthesis at the peak of S phase. These results provide insight into the relationship between Aβ25-35 and astrocyte cell cycling in AD.


COPD health care in Sweden - A study in primary and secondary care.
To map out-patients with Chronic Obstructive Pulmonary Disease (COPD) with special reference to patients suffering from acute exacerbations, and to describe COPD health care structure and process in Swedish clinical practice in a real life setting. Retrospective, non-interventional, epidemiological survey. 141 hospital based out patient clinics (OPC, n=30) and primary health care clinics (PC, n=111) were included in the structure evaluation. 1004 COPD diagnosed patients from 100 of the centres (OPC, n=26) participated in the process evaluation. All Swedish OPC (n=40) and a random sample of 180 PC were asked to answer a questionnaire regarding COPD care. In addition, data from 10 randomly selected patients with a documented COPD disease were analysed from the centres. Spirometers were available at all OPCs and at 99% of the PCs. Spirometry had been performed in 52% of PC-patients and in 89% of OPC-patients during the last 2 years prior to the study. More severe patients, as judged by investigator and lung function data, were treated at OPCs than at PCs. Physiotherapists, occupational therapists and dieticians were available at >80% of centres. Exacerbation rate was higher at PCs without a specialized nurse, 2.2/year versus 0.9/year at centres with a specialized nurse. Special attention to COPD, marked by a specialised nurse in primary care improves the quality, as assessed by a lower number of exacerbations. The structure of COPD care in Sweden for diagnosed individuals seems satisfactory, but could be improved mainly through higher availability and educational activities.


Greater use of preventive services in U.S. health care could save lives at little or no cost.
There is broad debate over whether preventive health services save money or represent a good investment. This paper analyzes the estimated cost of adopting a package of twenty proven preventive services--including tobacco cessation screening, alcohol abuse screening, and daily aspirin use--against the estimated savings that could be generated. We find that greater use of proven clinical preventive services in the United States could avert the loss of more than two million life-years annually. What's more, increasing the use of these services from current levels to 90 percent in 2006 would result in total savings of $3.7 billion, or 0.2 percent of U.S. personal health care spending. These findings suggest that policy makers should pursue options that move the nation toward greater use of proven preventive services.


Exercise plasma catecholamines in dogs: role of adrenals and cardiac nerve endings.
The plasma norepinephrine concentration (NE, ng . ml-1) in the pulmonary artery of dogs increased above resting values (0.22 +/- 0.04) for moderate (0.53 +/- 0.06) and severe exercise (1.45 +/- 0.23) and during prolonged exercise of moderate intensity (2.06 +/- 0.14). The plasma epinephrine concentration (E) increased above resting values (0.14 +/- 0.04) for severe exercise only (0.76 +/- 0.10) or when moderate exercise was prolonged (1.81 +/- 0.24). The E response, which appeared greater than that found in humans, is probably related to the species difference in the vasomotor response to exercise between humans and dogs, the latter not being subjected to compensatory vasoconstriction in nonworking areas. The activity of the adrenal medulla is confirmed by the plasma catecholamine (CA) gradient between proximal and distal posterior vena cava at rest (0.20 +/- 0.09) and during short- (0.35 +/- 0.08) and long-duration exercise (1.37 +/- 0.23). On the contrary, the heart is not a source of plasma CA in dogs: coronary sinus CA did not exceed aortic CA at rest and for moderate exercise and was lower than aortic CA for severe exercise (4.80 +/- 0.25 vs. 6.55 +/- 0.76 ng . ml-1).. The sources of plasma NE remain unclear in exercising dogs. Significant amounts of NE may be released by the adrenal medulla.


Choanal atresia: an unusual serious complication of complementary and alternative medical treatment.
The use of complementary and alternative medicine (CAM) is common among patients with chronic, long-standing nasal disease. Complications resulting from inappropriate CAM practices are sometimes reported, but serious complications such as choanal atresia and stenosis are rare. We report a case of choanal atresia and stenosis due to herbal drug (ie, chemical) cauterization of the nasal cavity in a 39-year-old man. We reviewed the literature on why patients previously given conventional treatment seek alternative therapies. The patient underwent surgical intervention to relieve choanal atresia and stenosis. The postoperative course was unremarkable, and follow-up for 1 year revealed no evidence of restenosis. Choanal atresia and stenosis resulting from CAM treatment are rare. Otolaryngologists should be aware of possible complications occurring in patients receiving such treatments.


Infection by discordant strains of HIV-1 markedly enhances the neutralizing antibody response against heterologous virus.
High-risk cohorts in East Africa and the United States show rates of dual HIV-1 infection--the concomitant or sequential infection by two HIV-1 strains--of 50% to 100% of those of primary infection, and our normal-risk HIV-positive cohort in Cameroon exhibits a rate of dual infection of 11% per year, signifying that these infections are not exceptional. Little is known regarding the effect of dual infections on host immunity, despite the fact that they provide unique opportunities to investigate how the immune response is affected when challenged with diverse HIV-1 antigens. Using heterologous primary isolates, we have shown here that dual HIV-1 infection by genetically distant strains correlates with significantly increased potency and breadth of the anti-HIV-1 neutralizing antibody response. When the neutralization capacities of sequential plasma obtained before and after the dual infection of 4 subjects were compared to those of matched plasma obtained from 23 singly infected control subjects, a significant increase in the neutralization capacity of the sequential sample was found for 16/28 dually infected plasma/virus pairs, while only 4/159 such combinations for the control subjects exhibited a significant increase (P < 0.0001). Similarly, there was a significant increase in the plasma dilution capable of neutralizing 50% of virus (IC(50)) for 18/24 dually infected plasma/virus pairs, while 0/36 controls exhibited such an increase (P < 0.0001). These results demonstrate that dual HIV-1 infection broadens and strengthens the anti-HIV-1 immune response, suggesting that vaccination schemes that include polyvalent, genetically divergent immunogens may generate highly protective immunity against any HIV-1 challenge strain.


Electrical properties of mineral surfaces for increasing water sorption.
Thin films of nanostructures alter the electrical properties of mineral surfaces and thereby affect reactions with charged species such as metal ions and biological cells. In this study, electric-force microscopy is used to probe the electrical properties of a heterogeneous layout of manganese oxide nanostructures grown as a film on a MnCO3 substrate. The role of water sorption is examined by carrying out experiments for increasing relative humidity (RH). Electric-force images collected with a negative dc tip bias show that the apparent heights of the nanostructures decrease from +3.4 nm at 16% RH to +0.7 nm at 33% RH to -5.6 nm at 74% RH, although the topographic height is 2.3 nm regardless of RH. The apparent heights for a positive dc bias also decrease with increasing RH from -3.5 nm at 16% RH to -8.9 nm at 74%. The explanation for these trends is that the dominant electric-force transitions with increasing RH from an electrostatic force attributable to surface potential to a polarization force arising from hydrated, mobile surface ions including Mn2+ and CO3(2-). The positive-to-negative trend in apparent heights implies that either the density or the intrinsic mobility (or both) of mobile ions over the substrate exceeds that over the nanostructures, implying increased water sorption over the former compared to the latter. Ridges around the perimeter of the nanostructures also develop above 40% RH for images collected using a negative dc tip bias. A tip-induced gradient of net positive charge near the nanostructure edges, which implies the nonequivalence of cations and anions there, explain this observation. The findings of this study show that thin films of nanostructures on mineral surfaces have complex but measurable RH-dependent electrical properties.


Phenotypic heterogeneity in the stargazin allelic series.
The stargazer mutant mouse is characterized by its ataxic gait, head tossing, and absence seizures. The mutation was identified in the gamma 2 subunit gene of the high voltage-dependent calcium channel, Cacng2. Subsequently, two allelic variants of stargazer have arisen, waggler and stargazer 3J. In this study, we have compared these new alleles to the original stargazer allele. All three mutations affect the Cacng2 mRNA levels as they all arise from disruptions within the introns of this gene. Our results show that the mutations cause reduced Cacng2 mRNA and protein levels. Stargazer and waggler mice have the least amount of mRNA and undetectable protein, whereas stargazer 3J appears to be the mildest allele, both in terms of the phenotype and protein expression. Electroencephalographic (EEG) analysis confirmed that stargazer has frequent spike-wave discharges (SWDs); the average duration of each discharge burst is 5 seconds and recurs every minute. The waggler allele causes a greater variation in SWD activity depending on the individual mouse, and the stargazer 3J mouse has no SWDs. The preliminary characterization of this heterogeneous allelic series provides a basis to explore more biochemical and physiological parameters relating to the role of the Cacng2 product in calcium channel activity, AMPA receptor localization, and cerebellar disturbances.


Long-term results of therapy with interferon-alpha for type II essential mixed cryoglobulinemia.
Severe type II essential mixed cryoglobulinemia (EMC) bears a poor prognosis. Treatment with corticosteroids and/or cytotoxic drugs infrequently results in long-term remissions, and is associated with significant toxicity. We conducted a prospective study with interferon (IFN) in 21 patients with severe type II EMC unresponsive to immunosuppressive regimens. They were treated with recombinant IFN-alpha 2a (18 patients) or with natural IFN-beta (three patients), alone, at a dosage of 3 megaunits (MU)/d for 3 months, followed by 3 MU every other day as maintenance. We observed 11 complete remissions, five partial remissions, and five minor responses. Of 16 patients observed for more than 1 year, 11 remained in remission for 14 to 40 months; five of them remained in complete remission for 18 to 40 months after withdrawal of treatment. Four patients discontinued treatment because of side effects. In four patients who relapsed while on maintenance therapy with recombinant IFN-alpha 2a, remission could be reinduced by treatment with natural IFN-alpha. The response rate of 77% achieved in this study prompts the use of IFN-alpha as a first-choice drug for type II EMC.


[GENES ALLELE STATUS OF ANGIOTENSINCONVERTING ENZYME (I/D) AND ENDOTHELIAL NITRIC OXIDE SYNTHASE (894 G > T) IN PATIENTS WITH ACUTE CORONARY SYNDROME].
The association of genes polymorphism of angiotensin-converting enzyme ACE (I/D) and endothelial nitric oxide synthase eNOS (894 G > T) with acute myocardial infarction (MI) among residents of North Bukovina region was evaluated. II/GG and ID/GG haplotypesre associated with more frequent presence of Q-MI, with localization on anterior wall and primary appearance. ID/TT, or II/TG haplotypes are associated with the presence of a severe re-Q-MI, with localization on the posterior wall. ID/TG variant is associated in 93.7% of cases with Q-MI, regardless of its location and times of occurrence. ID/TG increased relative risk of Q-MI by 2,93 times (OR = 4,79; P = 0,002), which confirmed the severity of the disease and increases the risk of MI inanterior and higher in posterior walls of the left ventricle (OR = 4.31; P = 0.007 and OR = 4.6; P = 0.005, respectively) increases the likelihood of the first Ml by 2.88 times (OR = 4.62; P = 0.003) and its re-occurrence or recurrence--by 2.67 times (OR = 4; P = 0.022). Mutations absence: in haplotypes (II/GG) is a protective factor of Q-MI appearance (OR = 0.19; P = 0.004) and makes the chances for the first MI the lowest in observed population (OR = 0.36; P = 0.045).


Interventional MRI: tapering improves the distal sensitivity of the loopless antenna.
The "loopless antenna" is an interventional MRI detector consisting of a tuned coaxial cable and an extended inner conductor or "whip". A limitation is the poor sensitivity afforded at, and immediately proximal to, its distal end, which is exacerbated by the extended whip length when the whip is uniformly insulated. It is shown here that tapered insulation dramatically improves the distal sensitivity of the loopless antenna by pushing the current sensitivity toward the tip. The absolute signal-to-noise ratio is numerically computed by the electromagnetic method-of-moments for three resonant 3-T antennae with no insulation, uniform insulation, and with linearly tapered insulation. The analysis shows that tapered insulation provides an approximately 400% increase in signal-to-noise ratio in trans-axial planes 1 cm from the tip and a 16-fold increase in the sensitive area as compared to an equivalent, uniformly insulated antenna. These findings are directly confirmed by phantom experiments and by MRI of an aorta specimen. The results demonstrate that numerical electromagnetic signal-to-noise ratio analysis can accurately predict the loopless detector's signal-to-noise ratio and play a central role in optimizing its design. The manifold improvement in distal signal-to-noise ratio afforded by redistributing the insulation should improve the loopless antenna's utility for interventional MRI.


The impact of equol-producing status in modifying the effect of soya isoflavones on risk factors for CHD: a systematic review of randomised controlled trials.
Recent studies suggest that the ability to produce equol, a metabolite of the soya isoflavone daidzein, is beneficial to coronary health. Equol, generated by bacterial action on isoflavones in the human gut, is biologically more potent than dietary sources of isoflavones. Not all humans are equol producers. We investigated whether equol-producing status is favourably associated with risk factors for CHD following an intervention by dietary soya isoflavones. We systematically reviewed randomised controlled trials (RCT) that evaluated the effect of soya isoflavones on risk factors for CHD and that reported equol-producing status. We searched PubMed, EMBASE, Ovid Medline and the Cochrane Central Register for Controlled Trials published up to April 2015 and hand-searched bibliographies to identify the RCT. Characteristics of participants and outcomes measurements were extracted and qualitatively analysed. From a total of 1671 studies, we identified forty-two articles that satisfied our search criteria. The effects of equol on risk factors for CHD were mainly based on secondary analyses in these studies, thus with inadequate statistical power. Although fourteen out of the forty-two studies found that equol production after a soya isoflavone intervention significantly improved a range of risk factors including cholesterol and other lipids, inflammation and blood pressure variables, these results need further verification by sufficiently powered studies. The other twenty-eight studies primarily reported null results. RCT of equol, which has recently become available as a dietary supplement, on CHD and its risk factors are awaited.


Impact of time-dependent nonaxisymmetric velocity perturbations on dynamo action of von Kármán-like flows.
We present numerical simulations of the kinematic induction equation in order to examine the dynamo efficiency of an axisymmetric von Kármán-like flow subject to time-dependent nonaxisymmetric velocity perturbations. The numerical model is based on the setup of the French von Kármán-sodium dynamo (VKS) and on the flow measurements from a water experiment conducted at the University of Navarra in Pamplona, Spain. The principal experimental observations that are modeled in our simulations are nonaxisymmetric vortexlike structures which perform an azimuthal drift motion in the equatorial plane. Our simulations show that the interactions of these periodic flow perturbations with the fundamental drift of the magnetic eigenmode (including the special case of nondrifting fields) essentially determine the temporal behavior of the dynamo state. We find two distinct regimes of dynamo action that depend on the (prescribed) drift frequency of an (m=2) vortexlike flow perturbation. For comparatively slowly drifting vortices we observe a narrow window with enhanced growth rates and a drift of the magnetic eigenmode that is synchronized with the perturbation drift. The resonance-like enhancement of the growth rates takes place when the vortex drift frequency roughly equals the drift frequency of the magnetic eigenmode in the unperturbed system. Outside of this small window, the field generation is hampered compared to the unperturbed case, and the field amplitude of the magnetic eigenmode is modulated with approximately twice the vortex drift frequency. The abrupt transition between the resonant regime and the modulated regime is identified as a spectral exceptional point where eigenvalues (growth rates and frequencies) and eigenfunctions of two previously independent modes collapse. In the actual configuration the drift frequencies of the velocity perturbations that are observed in the water experiment are much larger than the fundamental drift frequency of the magnetic eigenmode that is obtained from our numerical simulations. Hence, we conclude that the fulfillment of the resonance condition might be unlikely in present day dynamo experiments. However, a possibility to increase the dynamo efficiency in the VKS experiment might be realized by an application of holes or fingers on the outer boundary in the equatorial plane. These mechanical distortions provoke an anchorage of the vortices at fixed positions thus allowing an adjustment of the temporal behavior of the nonaxisymmetric flow perturbations.


Responsible Behavior With Younger Children: Results From a Pilot Randomized Evaluation of a School-Based Child Sexual Abuse Perpetration Prevention Program.
Many efforts to prevent child sexual abuse (CSA) aim to teach children strategies for recognizing, resisting, and reporting victimization. There is limited evidence that victimization-focused efforts actually prevent CSA. Moreover, these efforts often overlook the fact that many children and adolescents engage in problem sexual behavior against younger children. Responsible Behavior with Younger Children (RBYC) is a novel universal school-based perpetration-focused intervention that aims to prevent the onset of inappropriate, harmful, or illegal sexual behavior by adolescents against younger children.1 Responsible behavior with younger children was designed to provide adolescents and their parents with the knowledge and tools to help adolescents interact appropriately with younger children and avoid CSA behaviors. In this paper we describe intervention development, summarize lessons learned from implementing RBYC in four urban schools, and report results from our pilot randomized waitlist-controlled trial (RCT) with 160 6th and 7th grade students. Results indicate RBYC was associated with increased accuracy in youth knowledge about CSA and CSA-related laws, and with increased behavioral intention to avoid or prevent CSA with younger children and peer sexual harassment. Although the sample was small and the effects were relatively modest, the findings do suggest that RBYC holds promise for preventing the onset of problem sexual behavior.


The timing and location of glial cell line-derived neurotrophic factor expression determine enteric nervous system structure and function.
Ret signaling is critical for formation of the enteric nervous system (ENS) because Ret activation promotes ENS precursor survival, proliferation, and migration and provides trophic support for mature enteric neurons. Although these roles are well established, we now provide evidence that increasing levels of the Ret ligand glial cell line-derived neurotrophic factor (GDNF) in mice causes alterations in ENS structure and function that are critically dependent on the time and location of increased GDNF availability. This is demonstrated using two different strains of transgenic mice and by injecting newborn mice with GDNF. Furthermore, because different subclasses of ENS precursors withdraw from the cell cycle at different times during development, increases in GDNF at specific times alter the ratio of neuronal subclasses in the mature ENS. In addition, we confirm that esophageal neurons are GDNF responsive and demonstrate that the location of GDNF production influences neuronal process projection for NADPH diaphorase-expressing, but not acetylcholinesterase-, choline acetyltransferase-, or tryptophan hydroxylase-expressing, small bowel myenteric neurons. We further demonstrate that changes in GDNF availability influence intestinal function in vitro and in vivo. Thus, changes in GDNF expression can create a wide variety of alterations in ENS structure and function and may in part contribute to human motility disorders.


A retrospective review over 1999 to 2007 of head, shoulder and knee soft tissue and fracture dislocation injuries and associated costs for rugby league in New Zealand.
King et al. reported that of 5 941 moderate to serious claims resulting in medical treatment for rugby league injuries, the knee, shoulder, and head and neck body sites and soft tissue and fracture-dislocation injuries were most frequent and costly in the New Zealand national no-fault injury compensation corporation database during 1999 to 2007. However, additional analyses of knee, shoulder and head and neck body sites by soft tissue and fracture-dislocation injury types was required to enable a greater understanding of the nature of injuries most likely to be seen by sports medical personnel dealing with rugby league players. From 1999 to 2007 the injury claims and costs for head and neck soft tissue, fracture-dislocations, shoulders soft tissue significantly increased. Knee soft tissue injury claims and costs significantly decreased from 1999 to 2007. There was no significant difference in knee fracture-dislocation injury claims but there was a significant increase in knee fracture-dislocation injury costs from 1999 to 2007. Changes in the nature of injuries may be related to changes in defensive techniques employed in rugby league during this time. Sports medical personnel dealing with rugby league players should focus their injury prevention strategies on reducing musculoskeletal injuries to the head and shoulder. There should be a focus on increasing awareness of correct tackling technique, head injury awareness and management of suspected cervical spine injuries.


Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype.
Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)-targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor-negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor-negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.


Organophosphorus flame retardants and plasticizers in marine and fresh water biota and in human milk.
The levels and relative proportions of 11 organophosphorus flame retardants and plasticizers (OPs), some of which are reportedly toxic to aquatic organisms, were investigated in human breast milk and samples of fish and mussels from Swedish lakes and coastal areas in order to assess spatial differences in environmental exposure and spatial and temporal differences in human exposure. Some of the biota samples were collected at locations with known potential sources of OPs, but most were collected in background locations. Tris-2-chloroisopropyl phosphate (TCPP) and triphenyl phosphate (TPP) dominated in the biota with levels ranging from 170 to 770 ng g(-1) for TCPP in perch and between 21 and 180 ng g(-1) for TPP. In milk samples, TCPP (median 45 ng g(-1)) and tributyl phosphate (median 12 ng g(-1)) were the most frequently occurring OPs. Among samples of fish from background locations, the concentrations and profiles of most OPs were quite similar, indicating that their sources were diffuse. However, in fish from sample locations near known sources, there were marked differences in OP concentrations and profiles. Fish from a stream receiving surface water from Arlanda airport displayed high levels of OPs (10 200 ng g(-1)) that are commonly used in aircraft hydraulic fluids. Fish collected at points 1 or 2 km downstream of sewage treatment plants showed significantly higher levels of tris(2-butoxyethyl) phosphate (TBEP), one of the most typically abundant OP in effluents from such plants. In the milk samples obtained from women in different towns no distinct differences were detected in OP concentrations or profiles. However, the levels of TBEP tended to be higher in milk collected 10 years ago than in milk collected more recently. However, human exposure to OPs through eating fish or to breastfeeding babies seems to be of minor importance in relation to other potential sources, such as indoor dust inhalation and ingestion.


[Effect of dihydrocytochalasin B on the induction of DNA synthesis by epidermal growth factor, insulin and serum in Swiss 3T3 cells].
The addition of a microfilament-disorganizing agent--dihydrocytochalasin B B (5-10 micrograms/ml)--to to quiescent confluent or sparse (in 0.5% serum) Swiss 3T3 cells, 1-2 hours prior to stimulation, inhibited the initiation of DNA synthesis induced by an epidermal growth factor (7.5-10 ng/ml) and insulin (0.5-1.0 micrograms/ml), but exerted a low effect on serum stimulation. DNA synthesis was measured 21-23 hours after the growth factor administration by 14C-thymidine incorporation in acid-insoluble material and the ratio of this fraction to exogenous thymidine uptake. Moreover, the polar solvent dimethylsulfoxide, present in culture medium at low concentration (0.1-0.5%), also caused a decrease in the basal level of 14C-thymidine incorporation in resting cells, and a less decrease in the induced incorporation.


Confronting Colonialism in Canadian Dietetics Curricula.
Many Canadian universities have committed to becoming more accountable to Indigenous Peoples by confronting the systemic, historical, and ongoing colonialism and anti-Indigenous racism that shape their campuses. In this Perspective in Practice piece, we invite the field of dietetics to consider how colonialism has shaped dietetics research, teaching, and practice. We also consider how we might transform the field of dietetics in ways that accept settler responsibility for interrupting racism and colonial harm; support the resurgence of Indigenous food and health practices; and recognise the connections between struggles to ensure that Indigenous Peoples can access culturally appropriate food and health care, and struggles for Indigenous sovereignty and self-determination. We do this by reviewing the history of the dietetics field, examining critical responses to existing Indigenisation and decolonisation efforts, and reflecting on recent changes to required dietetics competencies. We argue that curricula in dietetics programmes must teach the history of the colonial food system and equip students to identify and interrupt the individual and institutional colonial dynamics that contribute to the ongoing dispossession of Indigenous Peoples' lands and food sources and negatively impact Indigenous patients.


FLEA PARASITISM AND HOST SURVIVAL IN A PLAGUE-RELEVANT SYSTEM: THEORETICAL AND CONSERVATION IMPLICATIONS.
Plague is a bacterial zoonosis of mammalian hosts and flea vectors. The disease is capable of ravaging rodent populations and transforming ecosystems. Because plague mortality is likely to be predicted by flea parasitism, it is critical to understand vector dynamics. It has been hypothesized that paltry precipitation and reduced vegetative production predispose herbivorous rodents to malnourishment and flea parasitism, and flea parasitism varies directly with plague mortality. We evaluated these hypotheses on five colonies of Utah prairie dogs (UPDs; Cynomys parvidens), on the Awapa Plateau, Utah, US, in 2013-16. Ten flea species were identified among 3,257 fleas from UPDs. These 10 flea species parasitize prairie dogs, mice, rats, voles, ground squirrels, chipmunks, and marmots, all known hosts of plague. The abundance of fleas on individual UPDs (1,198 observations) varied inversely with UPD body condition; fleas were most abundant on lightweight, malnourished UPDs. Flea abundance on UPDs was highest in dry years that were preceded by wet years. Increased precipitation and soil moisture in the prior year might generate humid microclimates in UPD burrows (that could facilitate flea survival and reproduction) and paltry precipitation in the current year could predispose UPDs to malnourishment and flea parasitism. Annual re-encounter rates for UPDs (1,072 observations) were reduced in wetter years preceded by drier years; reduced precipitation and vegetative production might kill UPDs, and increased flea densities in drier years could provide conditions for plague transmission (and UPD mortality) when moisture returns. Re-encounter rates were reduced for UPDs carrying at least one flea compared to UPDs with no detected fleas. These results support the hypothesis that reduced precipitation in the current year predisposes UPDs to flea parasitism. Our results also suggest a link between flea parasitism and UPD mortality. Given documented connections between flea parasitism and plague transmission, our results point toward an effect of flea parasitism on plague-related deaths for individual UPDs, a phenomenon rarely investigated in nature.


The fourth trimester: a critical transition period with unmet maternal health needs.
After childbirth, most American women are not scheduled for follow-up care for 6 weeks, and this visit is poorly attended. Many new mothers feel unprepared for the common health issues they encounter and are uncertain of whom to contact. To improve care, the 4th Trimester Project is bringing together mothers, health care providers, and other stakeholders to explore what families need most from birth to 12 weeks postpartum. Eighty-seven individuals convened in March 2016 in Chapel Hill, NC. Four major topic areas emerged: (1) the intense focus on women's health prenatally is unbalanced by infrequent and late postpartum care; (2) medical practice guidelines often do not align with women's experiences and constraints; (3) validation of women as experts of their infants and elevating their strengths as mothers is necessary to achieve health goals; and (4) mothers need comprehensive care, which is difficult to provide because of numerous system constraints. Considerations for improving postpartum services include enabling more convenient care for families that is holistic, culturally appropriate, conversation based, and equitable. Maternal health issues in the fourth trimester intersect and can compound one another. Enhanced collaboration among health care providers may improve the focus of clinical interactions to address the interrelated health issues most important to women.


Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor).
Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or beta-catenin genes, resulting in beta-catenin protein stabilization. Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modulates the formation of colonic neoplasia, especially in cases due to mutations resulting in beta-catenin stabilization. Human aggressive fibromatoses and lesions from the Apc+/Apc1638N mouse (a murine model for Apc-driven fibromatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in reduced proliferation in human tumor cell cultures. Breeding mice with Cox-2-/- mice resulted in no difference in number of aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%. Mice fed various COX blocking agents also showed a decline in tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion. COX-2 partially regulates proliferation due to beta-catenin stabilization in aggressive fibromatosis. Although COX blockade alone does not cause tumor regression, this data suggests that it may have a role as an adjuvant therapy to slow tumor growth in this lesion.


Night shift work and the risk of endometrial cancer.
Melatonin has several oncostatic properties, including possible anti-estrogenic and anti-aromatase activity, and seems to be linked with fat metabolism. Night workers have lower levels of melatonin, which may predispose them to develop cancer. Endometrial cancer risk is influenced significantly by hormonal and metabolic factors; therefore, we hypothesize that night workers may have an increased risk of endometrial cancer. Of the 121,701 women enrolled in a prospective cohort study, 53,487 women provided data on rotating night shift work in 1988 and were followed through on June 1, 2004. A total of 515 women developed medical record-confirmed invasive endometrial cancer. We used Cox regression models to calculate multivariate relative risks (MVRRs), controlling for endometrial cancer risk factors. Women who worked 20+ years of rotating night shifts had a significantly increased risk of endometrial cancer [MVRR, 1.47; 95% confidence interval (95% CI), 1.03-1.14]. In stratified analyses, obese women working rotating night shifts doubled their baseline risk of endometrial cancer (MVRR, 2.09; 95% CI, 1.24-3.52) compared with obese women who did no night work, whereas a nonsignificant increase was seen among non-obese women (MVRR, 1.07; 95% CI, 0.60-1.92). Women working rotating night shifts for a long duration have a significantly increased risk of endometrial cancer, particularly if they are obese. We speculate that this increased risk is attributable to the effects of melatonin on hormonal and metabolic factors. Our results add to growing literature that suggests women who work at night may benefit from cancer prevention strategies.


Direction and rate of socket wear in Charnley low-friction arthroplasty.
Twenty-two high-density polyethylene sockets from Charnley low-friction arthroplasties have been studied. Acrylic casts and shadowgraph techniques were used to measure both the real and radiographic rates of wear; these rates showed a significant correlation. In the sagittal plane, nine of the sockets had worn lateral to a line drawn vertically from the centre of curvature of the socket, 12 had worn medial to that line and only one was worn exactly in the line. In the coronal plane, nine sockets had worn in front of a similar vertical line, two behind that line and 11 had worn exactly in the line. Evidence of impingement of the neck of the stem onto the rim of the socket was found in 14 patients; this is considered to be one of the causes of socket loosening. The obvious solution is to reduce the diameter of the neck of the stem from 12.5 mm to 10 mm; provided that it is made of cold-formed, high nitrogen-content stainless steel, this narrower neck is strong enough not to fracture.


Lethal and sublethal side-effect assessment supports a more benign profile of spinetoram compared with spinosad in the bumblebee Bombus terrestris.
This study was undertaken to identify the potential side effects of the novel naturalyte insecticide spinetoram in comparison with spinosad on the bumblebee Bombus terrestris L. The potential lethal effects together with the ecologically relevant sublethal effects on aspects of bumblebee reproduction and foraging behaviour were evaluated. Bumblebee workers were exposed via direct contact with wet and dry residues under laboratory conditions to spinetoram at different concentrations, starting from the maximum field recommended concentration (MFRC) and then different dilutions (1/10, 1/100, 1/1000 and 1/10 000 of the MFRC), and compared with spinosad. In addition, the side effects via oral exposure in supplemented sugar water were assessed. Direct contact of B. terrestris workers with wet residues of spinosad and spinetoram showed spinetoram to be approximately 52 times less toxic than spinosad, while exposure to dry residues of spinetoram was about 8 times less toxic than exposure to those of spinosad. Oral treatment for 72 h (acute) indicated that spinetoram is about 4 times less toxic to B. terrestris workers compared with spinosad, while exposure for a longer period (i.e. 11 weeks) showed spinetoram to be 24 times less toxic. In addition, oral exposure to the two spinosyns resulted in detrimental sublethal effects on bumblebee reproduction. The no observed effect concentration (NOEC) for spinosad was 1/1000 of the MFRC, and 1/100 of the MFRC for spinetoram. Comparison between the chronic exposure bioassays assessing the sublethal effects on nest reproduction, with and without allowing for foraging behaviour, showed that the respective NOEC values for spinosad and spinetoram were similar over the two bioassays, indicating that there were no adverse effects by either spinosyn on the foraging of B. terrestris workers. Overall, the present results indicate that the use of spinetoram is safer for bumblebees by direct contact and oral exposure than the use of spinosad, and therefore it can be applied safely in combination with B. terrestris. Another important conclusion is that the present data provide strong evidence that neither spinosyn has a negative effect on the foraging behaviour of these beneficial insects. However, before drawing final conclusions, spinetoram and spinosad should also be evaluated in more realistic field-related situations for the assessment of potentially deleterious effects on foraging behaviour with the use of queenright colonies of B. terrestris.


Pharmacological aspects of shaking behavior produced by TRH, AG-3-5, and morphine withdrawal.
In virtually all fur-coated and feathered animals, shaking movements of the body, similar to that made by a dog when wet, occur in response to irritation of the skin or in response to sensations of intense cold. Vigorous shaking movements occur in rats undergoing opiate withdrawal. I was led by this observation to investigations on the pharmacology of agents that stimulate or inhibit shaking. Thyrotropin-releasing hormone, injected centrally at submicrogram doses, produced in nondependent, barbiturate-anesthetized animals, shaking behavior identical in its general features to that of morphine withdrawal. AG-3-5 (1-[2-hydroxyphenyl]-4[3-nitrophenyl]-1,2,3,6-tetrahydropyrimidine-2-one), another chemical stimulant of shaking, produced specific sensations of cold in man by a peripheral site of action. In this context, it should be noted that sensations of cold, and the associated emotional discomfort, are conspicuous symptoms of opiate withdrawal in man. Shaking movements elicited by a variety of stimuli were inhibited by central administration of nanomolar doses of drugs that act as agonists on opiate, muscarinic, and alpha-adrenergic receptors. These observations may provide information on a) the identity of substances in brain that, when released, provoke opiate withdrawal signs and symptoms; b) the chemical nature of substances that stimulate peripheral cold receptors; and c) the pharmacologic classification of centrally acting agents that attenuate withdrawal and produce antinociception.


Door locking and exit security measures on acute psychiatric admission wards.
Locking the exit doors of psychiatric wards is believed to reduce the risk of patients absconding. The aims of the study were to investigate both the prevalence of door locking and other exit security measures on UK admission wards, as well as whether door locking appears to be effective in keeping inpatients in. A cross-sectional survey on 136 acute psychiatric wards in the UK was conducted, in which a range of data on patients, staff, and conflict and containment events, including door locking and absconding, were collected from shift to shift during a period of 6 months. About one-third of the participating wards (30%) operated with their ward exit door permanently locked, whereas another third (34%) never locked the ward door. Univariate analyses suggested little association between exit security measures and absconding. A more robust multilevel statistical analysis, however, did indicate a reduction of about 30% of absconding rates when the ward door was locked the entire shift. Although locking the ward door does seem to reduce absconding to a certain extent, it far from completely prevents it. As it may be unrealistic to strive for a 100% absconding-proof ward, alternative measures for door locking to prevent absconding are discussed.


Alpha- and beta-globins of the anemic Belgrade laboratory rat. I. Status of alpha- and beta-globins in bone marrow and spleen.
In this study we have demonstrated that the bone marrow of the anemic Belgrade laboratory (b/b) rat, as the primary site of erythropoiesis, has a decreased globin polypeptide synthesis in total protein cell extracts. Therefore, it is the source of red blood cells containing decreased amounts of globin mRNAs and polypeptides. In spite of the fact that the b/b rat shows a splenomegaly, the spleen is not capable of compensating for the anemic state. Spleen erythroid cells are defective in differentiation and contain a decreased share of globin polypeptides in total protein cell extracts compared to the control. Spleen cells are also characterized by a drastic imbalance of alpha- to beta-globin resulting in the beta-globin chains surplus.


Enzymatic Photodecarboxylation on Secondary and Tertiary Carboxylic Acids.
Photoenzymatic decarboxylation of bulky secondary and tertiary carboxylic acids catalyzed by engineered Chlorella variabilis fatty acid photodecarboxylase (CvFAP) is reported. Rational design and directed evolution of wild-type CvFAP are used to improve the reactivity and expand potential applications. Moreover, engineered CvFAP can catalyze light-driven kinetic resolution of α-substituted carboxylic acid. Our work sheds light on the production of chiral building blocks and bioactive molecules from bulky carboxylic acids via the photoenzymatic way.


State of the art: percutaneous tracheostomy in the intensive care unit.
Percutaneous tracheostomy is a commonly performed procedure for patients in the intensive care unit (ICU) and offers many benefits, including decreasing ICU length of stay and need for sedation while improving patient comfort, effective communication, and airway clearance. However, there is no consensus on the optimal timing of tracheostomy in ICU patients. Ultrasound (US) and bronchoscopy are useful adjunct tools to optimize procedural performance. US can be used pre-procedurally to identify vascular structures and to select the optimal puncture site, intra-procedurally to assist with accurate placement of the introducer needle, and post-procedurally to evaluate for a pneumothorax. Bronchoscopy provides real-time visual guidance from within the tracheal lumen and can reduce complications, such as paratracheal puncture and injury to the posterior tracheal wall. A step-by-step detailed procedural guide, including preparation and procedural technique, is provided with a team-based approach. Technical aspects, such as recommended equipment and selection of appropriate tracheostomy tube type and size, are discussed. Certain procedural considerations to minimize the risk of complications should be given in circumstances of patient obesity, coagulopathy, or neurologic illness. Herein, we provide a practical state of the art review of percutaneous tracheostomy in ICU patients. Specifically, we will address pre-procedural preparation, procedural technique, and post-tracheostomy management.


Opioid Reduction Following Interventional Procedures for Chronic Pain: A Synthesis of the Evidence.
The past decade has witnessed the tremendous growth of procedures to treat chronic pain, which has resulted in increased third-party scrutiny. Although most of these procedures appear to be associated with significant pain relief, at least in the short and intermediate term, their ability to improve secondary outcome measures, including function and work status is less clear-cut. One of these secondary outcome measures that has garnered substantial interest in the pain and general medical communities is whether interventions can reduce opioid intake, which is associated with significant risks that in most cases outweigh the benefits in the long term. In the article, we examine whether procedural interventions for chronic pain can reduce opioid intake. Most studies that have examined analgesic reduction as a secondary outcome measure have not separated opioid and nonopioid analgesics, and, among those studies that have, few have demonstrated between-group differences. Reasons for failure to demonstrate opioid reduction can be broadly classified into procedural, design-related, clinical, psychosocial, biological, and pharmacological categories, all of which are discussed. In the future, clinical trials in which this outcome is examined should be designed to evaluate this, at least on a preliminary basis.


Cellular defense against heat shock-induced oxidative damage by mitochondrial NADP+ -dependent isocitrate dehydrogenase.
Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Mitochondrial NADP+ -dependent isocitrate dehydrogenase (IDPm) produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of IDPm against heat shock in HEK293 cells, an embryonic kidney cell line, was investigated in control and cells transfected with the cDNA for IDPm, where IDPm activity was 6-7 fold higher than that in the control cells carrying the vector alone. Upon exposure to heat shock, the viability was lower and the protein oxidation, lipid peroxidation and oxidative DNA damage were higher in control cells as compared to HEK293 cells in which IDPm was over-expressed. We also observed the significant difference in the cellular redox status reflected by the endogenous production of reactive oxygen species, NADPH pool and GSH recycling between two cells. The results suggest that IDPm plays an important role as an antioxidant defense enzyme in cellular defense against heat shock through the removal of reactive oxygen species.


Whole Grain Consumption and Breast Cancer: A Case-Control Study in Women.
Whole grain consumption has long been associated with human health. However, its relationship with breast cancer remains not well understood and appreciated. The aim of this work was to evaluate the association between whole grain consumption and breast cancer in women. A case-control study was designed. Two hundred and fifty consecutive, newly diagnosed breast cancer female patients (56 ± 12 years) and 250 one-to-one age-matched controls were enrolled. A standardized, validated questionnaire assessing various sociodemographic, clinical, lifestyle, and dietary characteristics was applied through face-to-face interviews. Moreover, data on regular consumption of whole grains (i.e., never/rarely, 1-6 times/week, >7 times/week) were recorded. Overall dietary habits were assessed through the level of adherence to the Mediterranean diet using the MedDietScore (theoretical range 0-55). Whole grain consumption of more than 7 times/week was associated with a 0.49-fold (odds ratio = 0.49; 95% confidence interval, 0.29, 0.82) lower likelihood of having breast cancer, after adjustments were made. This study suggested that whole grain consumption more than 7 times/week was consistently associated with reduced risk of breast cancer.


Insulin-like growth factor system in patients with HIV infection: effect of exogenous growth hormone administration.
The purpose of this study was to characterize changes in the levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (BP) 1, 2, and 3 in HIV-infected adults throughout the course of their disease, and to assess the responsiveness of the IGF system components to growth hormone (GH) administration (6 mg/day) for 2 weeks. Healthy control study subjects (n = 10) were compared with patients who were either HIV-positive (n = 9), had AIDS without weight loss (n = 13), or had AIDS with >10% weight loss (n = 6), all of whom had been free of acute illness for at least 3 months. Under basal conditions, fasting serum concentrations of epinephrine, norepinephrine, cortisol, glucagon, insulin, IGF-I, and IGFBP-3 were not significantly different among the four groups. The serum concentrations of IGFBP-1 and IGFBP-2 were significantly higher in AIDS patients with wasting than in the other three groups (p < .05). In addition, there was a statistically significant positive correlation between the levels of IGFBP- 1 (p = .004) and IGFBP-2 (p = .03) and the stage of disease. Following GH administration, the serum concentrations of insulin and IGF-I were increased in all groups (p < .05). In addition, the increases in insulin levels correlated with stage of disease (p = .004). The responses of the IGFBPs were more variable. GH administration significantly increased the levels of IGFBP-3 in all groups except the patients with AIDS wasting, whereas the levels of IGFBP-1 were significantly decreased in controls and AIDS patients. These results demonstrate that there is a continuum of both elevations in the IGFBPs and altered metabolic responsiveness in patients infected with HIV that increases with the severity of the disease. These data also demonstrate that AIDS patients, who are free from secondary infection, respond to administration of GH by significantly increasing hepatic IGF-I production.


Learners misperceive the benefits of redundant text in multimedia learning.
Research on metacognition has consistently demonstrated that learners fail to endorse instructional designs that produce benefits to memory, and often prefer designs that actually impair comprehension. Unlike previous studies in which learners were only exposed to a single multimedia design, the current study used a within-subjects approach to examine whether exposure to both redundant text and non-redundant text multimedia presentations improved learners' metacognitive judgments about presentation styles that promote better understanding. A redundant text multimedia presentation containing narration paired with verbatim on-screen text (Redundant) was contrasted with two non-redundant text multimedia presentations: (1) narration paired with images and minimal text (Complementary) or (2) narration paired with minimal text (Sparse). Learners watched presentation pairs of either Redundant + Complementary, or Redundant + Sparse. Results demonstrate that Complementary and Sparse presentations produced highest overall performance on the final comprehension assessment, but the Redundant presentation produced highest perceived understanding and engagement ratings. These findings suggest that learners misperceive the benefits of redundant text, even after direct exposure to a non-redundant, effective presentation.


Optical filter architecture for approximating any 2 X 2 unitary matrix.
A new optical filter architecture and a new design methodology are presented for approximating any frequency-dependent 2 x 2 unitary matrix that consists of two coupled phase and amplitude responses. Design examples are provided for the compensation of polarization mode dispersion (PMD) by approximating the inverse of a synthesized fiber's Jones matrix. Compensation of the channel PMD over the signal bandwidth is demonstrated, as required for demultiplexing channels in a polarization-multiplexed system.


Rosai-Dorfman Disease and Unusual Local Invasive Presentation.
Rosai-Dorfman disease (RDD) is a rare medical condition with bilateral painless lymphadenopathy. We present the case of a young man diagnosed with a very unique presentation of Rosai-Dorfman disease. A 40-year-old African-American man presented with a firm, non-tender, progressive chest and neck mass appeared three months ago. Imaging of the neck demonstrated an 8.6-cm anterior neck subcutaneous soft tissue mass extending into the anterior mediastinum through the sternum with erosive changes in the sternum and the lesion is abutting the right common carotid artery and innominate vein and surrounds the medial aspect of the clavicles bilaterally. Ultrasound (US)-guided biopsy showed marked polytypic-appearing plasma cell proliferation associated with relatively prominent histiocytes with hemophagocytosis/emperipolesis and focal neutrophils. There were S100+ histiocytes; however, findings were not typical for RDD. As that biopsy was not diagnostic, incisional biopsy with adequate sampling was performed. Surgical pathology demonstrated a very abnormal infiltrate with prominent histiocytes including areas with the features of extranodal RDD. BRAF V600E immunohistochemistry (IHC) was negative. Modified radical neck dissection, proximal sternal resection and superior mediastinal nodal dissection surgery was recommended. However, the patient refused the procedure. Typical manifestations are lymphadenopathy with fever that our patient did not experience. Bone involvement happens in 5-10% of cases. There is not enough data about blood vessel invasion which make our case unique. Treatment plan is still controversial. Clinical monitoring is recommended if the symptoms are tolerable as regression has been reported in many cases (20-50%). Surgery is reserved for patients with vital organ involvement or extra-nodal disease.


Hand-held syringe as a portable plastic pump for on-chip continuous-flow PCR: miniaturization of sample injection device.
On-chip continuous-flow polymerase chain reactions (PCRs) generally require peripheral apparatus such as a pump for injecting a sample liquid into the fluidic channel. This makes the overall instrumentation bulky, limiting integration. In this study, we propose a new scheme for injecting a sample employing a hand-held syringe as a portable plastic pump, and apply it to an on-chip continuous-flow PCR. In the proposed injection scheme, sample actuation was realized inside a highly gas-permeable and blunt-ended fluidic conduit connected to a hand-held plastic syringe filled with compressed air. In this system, the degree of air diffusion via the walls of the gas-permeable conduit becomes greater in the anterior (closer to the outlet) end of the sample plug than the posterior (closer to the inlet) end, because a relatively larger quantity of air is retained inside the syringe at the posterior end of the sample plug. This creates a pressure gradient at the inlet and outlet of the fluidic conduit and propels the sample forward toward the outlet. Preliminary experiments were performed for the quantitative analyses and evaluation of the proposed sample injection scheme using gas-permeable silicone tubes. As practical applications, a 230 bp gene fragment from a plasmid vector and the first 282 bp of the interferon-beta (IFN-β) promoter from a human genomic DNA were successfully amplified on a microdevice coupled with a hand-held syringe as a portable sample actuation device, greatly enhancing device portability for on-site analyses.


Comparison of serum human Klotho levels and thiol/disulfide homeostasis in women with polycystic ovary syndrome and in healthy women.
Women with polycystic ovary syndrome (PCOS) have an increased cardiometabolic risk. Similarly, it was previously shown that atherosclerotic and cardiovascular risk is increased in the general population with lower serum Klotho levels. The aim of this study was to investigate the lotho and thiol/disulfide levels in women with non-obese PCOS compared to healthy controls and also to investigate the relationship of serum Klotho and thiol/disulfide homeostasis with cardiometabolic risk factors. In this prospective case control study, human serum alpha Klotho levels and thiol/disulfide homeostasis of women with PCOS aged between 19-33 were compared to their age and BMI matched non - PCOS healthy controls. In addition, the correlation of these molecules with other metabolic markers/measurements were also investigated. Metabolic parameters such as mean waist circumference, lipid accumulation product, visceral adiposity index, fasting insulin, homeostasis model assessment of insulin resistance and triglyceride values were higher in the PCOS group (p = 0.038, p = 0.008, p = 0.001, p = 0.001, p = 0.002 and p = 0.002, respectively) compared to controls. However, mean serum Klotho and native thiol levels (respectively p < 0.0001 and p = 0.038) were lower compared to controls. Correlation analysis revealed that serum Klotho levels were negatively correlated with BMI, waist circumference, disulphide/total thiol, disulphide/native thiol, HOMA-IR and LAP-index. Findings of decreased serum Klotho and native thiol values of the PCOS group compared to controls and the negative correlation of serum Klotho levels with metabolic markers supports the idea that decreased Klotho may be another mechanism by which cardiovascular risk is increased in women with PCOS.


Quantitative comparison of cytotoxicity of dental antiseptics to normal human oral keratinocytes in vitro.
The cytotoxicities of antiseptics used in dentistry were examined with normal human keratinocytes from the oral cavity by the uptake of neutral red (NR assay). The NR assay is a quantitative in vitro assay that distinguishes between viable, damaged or dead cells. Cultures from different individuals were established, and secondary cultures in serum-free medium were used. The amount of NR extracted from cells after a 3-hr uptake of the dye was linearly proportional to the number of cells exposed to the dye. The cytotoxicity of antiseptics used on mucous membranes in the oral cavity was determined from the dose-response curves of inhibition of NR uptake in cells treated with antiseptics for 2 days. As a quantitative measure of cytotoxicity, NR(50) (i.e. the concentration of antiseptics that resulted in a 50% decrease in NR uptake relative to untreated controls) was extrapolated from dose-response curves. The rank-order of cytotoxicities (NR(50)) was Hyamine (10% benzethonium chloride solution) > Hibitane (5% chlorhexidine gluconate solution) > acrinol (0.2% acrinol solution) > Iodine Carbol (liquefied phenol with 3% iodine) > iodine glycerin (glycerin with 10% iodine) > dilute iodine tincture (3% iodine solution) approximately iodine tincture (6% iodine solution) approximately Isodine (10% povidone-iodine solution) > Oxydol (3% hydrogen peroxide solution). These results provide useful estimates of relative toxicities of antiseptics to human cells, which can be compared with antimicro-organism activity to maximize therapeutic benefit with minimal toxicity.


A new angiostrongylid (Nematoda) species from the pulmonary arteries of Akodon azarae (Rodentia: Cricetidae) in Argentina.
Angiostrongylus morerai n. sp. (Nematoda: Angiostrongylidae) is described from the pulmonary arteries of Azara's grass mouse Akodon azarae (Rodentia: Cricetidae) in Argentina. It is distinguished from its congeners principally by the morphology of the dorsal ray, which is as long, or longer, than the externodorsals and has 2 long branches; the spicule lengths are also greater (400-465 microm). This is the first record of a metastrongyloid from sigmodontine rodents in Argentina.