Long-term outcomes of patients bridged to recovery with venoarterial extracorporeal life support.
Our study examines the long-term outcomes of patients discharged from the hospital without heart replacement therapy (HRT) after recovery from cardiogenic shock using venoarterial extracorporeal life support (VA-ECLS). We retrospectively reviewed 615 cardiogenic shock patients who recovered from VA-ECLS at our institution between January 2015 and July 2021. Of those, 166 patients (27.0%) who recovered from VA-ECLS without HRT were included in this study. Baseline characteristics, discharge labs, vitals, electrocardiograms and echocardiograms were assessed. Patients were contacted to determine vital status. The primary outcome was post-discharge mortality. Of 166 patients, 158 patients (95.2%) had post-discharge follow-up, with a median time of follow-up of 2 years (IQR: [1 year, 4 years]). At discharge, the median ejection fraction (EF) was 52.5% (IQR: [32.5, 57.5]). At discharge, 92 patients (56%) were prescribed β-blockers, 28 (17%) were prescribed an ACE inhibitor, ARB or ARNI, and 50 (30%) were prescribed loop diuretics. Kaplan-Meier analysis showed a 1-year survival rate of 85.6% (95% CI: [80.1%, 91.2%]) and a 5-year survival rate of 60.6% (95% CI: [49.9%, 71.3%]). A Cox regression model demonstrated that a history of congestive heart failure (CHF) was strongly predictive of increased mortality hazard (HR = 1.929; p = 0.036), while neither discharge EF nor etiology of VA-ECLS were associated with increased post-discharge mortality. Patients discharged from the hospital after full myocardial recovery from VA-ECLS support without HRT should have close outpatient follow-up due to the risk of recurrent heart failure and increased mortality in these patients.


Enhanced expression of inducible cyclooxygenase with age in murine macrophages.
Macrophages (Mphi) from old mice produce more PGE2 than those from young mice, contributing to the dysregulation of the immune and inflammatory responses with age. This study was conducted to determine the mechanisms of the age-associated increase in Mphi PGE2 production. PGE2 production is influenced by the availability of the substrate arachidonic acid and by activity of the enzyme cyclooxygenase (Cox). We demonstrate that when the substrate is not the limiting factor, Mphi from old mice have significantly higher LPS-stimulated Cox activity than young mice, indicating that the age-associated increase in PGE2 production is due to increased enzyme activity and not to changes in substrate level. Cox activity is determined by the enzyme level and requires hydroperoxide for activation. Of the two Cox isoforms, Cox 1 is constitutively expressed in nearly all cells; whereas Cox 2 is induced by a wide range of ligands. Analysis of accumulated and de novo synthesis of constitutive Cox 1 and inducible Cox 2 proteins showed no age-related difference in Cox 1 protein levels, but Mphi from old mice had higher accumulated and newly synthesized LPS-stimulated Cox 2 protein levels than young mice. Furthermore, Mphi from old mice had higher LPS-stimulated levels of Cox 2 mRNA compared with those from young mice. Clearly, the age-associated increase in LPS-stimulated PGE2 production is due to increased Cox activity resulting from higher Cox 2 protein and mRNA expression. These findings have significant implications for age-associated immune and inflammatory dysregulation as well as the development of preventive and therapeutic strategies against them.


Malaria.
Malaria is caused in humans by five species of single-celled eukaryotic Plasmodium parasites (mainly Plasmodium falciparum and Plasmodium vivax) that are transmitted by the bite of Anopheles spp. mosquitoes. Malaria remains one of the most serious infectious diseases; it threatens nearly half of the world's population and led to hundreds of thousands of deaths in 2015, predominantly among children in Africa. Malaria is managed through a combination of vector control approaches (such as insecticide spraying and the use of insecticide-treated bed nets) and drugs for both treatment and prevention. The widespread use of artemisinin-based combination therapies has contributed to substantial declines in the number of malaria-related deaths; however, the emergence of drug resistance threatens to reverse this progress. Advances in our understanding of the underlying molecular basis of pathogenesis have fuelled the development of new diagnostics, drugs and insecticides. Several new combination therapies are in clinical development that have efficacy against drug-resistant parasites and the potential to be used in single-dose regimens to improve compliance. This ambitious programme to eliminate malaria also includes new approaches that could yield malaria vaccines or novel vector control strategies. However, despite these achievements, a well-coordinated global effort on multiple fronts is needed if malaria elimination is to be achieved.


Diagnosis and management of acute lower gastrointestinal bleeding.
We review and summarize the most recent literature, including evidence-based guidelines, on the evaluation and management of acute lower gastrointestinal bleeding (LGIB). LGIB primarily presents in the elderly, often on the background of comorbidities, and constitutes a significant healthcare and economic burden worldwide. Therefore, acute LGIB requires rapid evaluation, informed decision-making, and evidence-based management decisions. LGIB management involves withholding and possibly reversing precipitating medications and concurrently addressing risk factors, with definitive diagnosis and therapy for the source of bleeding usually performed by endoscopic or radiological means. Recent advancements in LGIB diagnosis and management, including risk stratification tools and novel endoscopic therapeutic techniques have improved LGIB management and patient outcomes. In recent years, the various society guidelines on acute lower gastrointestinal bleeding have been revised and updated accordingly. By integrating the most recently published high-quality clinical studies and society guidelines, we provide clinicians with an up-to-date and comprehensive overview on acute LGIB diagnosis and management.


Configuration of redox gradient determines magnetotactic polarity of the marine bacteria MO-1.
Magnetotactic bacteria are capable of aligning and swimming along the geomagnetic field lines; such a behaviour is called magnetotaxis. Previous studies reported that bacteria in the northern hemisphere migrate preferentially towards the North Pole of the Earth's magnetic field (north-seeking, NS), whereas those in the southern hemisphere swim towards the South Pole (south-seeking, SS). The orientated swimming is thought to guide bacteria migrating downward to the favourable microaerobic or anaerobic regions in stratified water column or sediments. Recent identification of SS populations in northern hemisphere challenged the model of the adaptive value of magnetotaxis. To seek explanation for the apparent discrepancy, we analysed magnetotaxis polarity of axenic cultures under simulated growth conditions in hypomagnetic, northern-hemisphere-like or southern-hemisphere-like magnetic fields. We found that NS and SS cells could obviously coexist in hypomagnetic field and even, when the oxidation-reduction gradient configuration is suitable, in the geomagnetic field. These results reveal the selectivity of the redox gradient configuration on magnetotactic polarity of the cells and reconcile the discrepancy of the early reports.


[Adherence to oral nutrition supplements in hospitalized patients with clinical pathology-surgical].
Studies about the use of nutritional supplements suggest that acceptance is good, so that it is widely recognized and used by professionals. However, in clinical daily practice it seems to be not as much accepted as I seems. The aim of our study is to know the level of adherence to oral nutritional supplements and the main reasons for non-adherence in patients admitted for medical or surgical pathologies. An observational, prospective and single-center study was designed. Consecutive patients admitted to a high complexity hospital between August 2012 and May 2013 and with subjective global assessment category B were included. A daily supplement was indicated, the adherence was evaluated and the reasons for non-adherence were determined. Adherent patient was considered when ≥75% of the supplements was consumed. Of a total of 807 patients with subjective global assessment, 73 patients were prescribed oral nutritional supplements. The median age was 52 years (IQR 35-62), 58.9% was male, the median body mass index was 24.5 (IQR 22.5 to 27.3). A total of 489 supplements were indicated and a total of 371 were consumed. The median days of indication for the supplements per patient were 5 days (IQR 4-10) and the median consumed was 4 days per patient (IQR 1- 8). The adherence was 58.9% (43 patients). The reasons for non-adherence were: patients own digestive reasons in 5 patients (16.7%), intolerance to oral nutritional supplement in 18 patients (60%) and unjustified patient's refusal in 7 patients (23.3%). In patients admitted for clinical or surgical pathologies with subjective global assessment B, adherence to oral nutritional supplements was insufficient. Intolerance to supplements was the most frequent reason of non-adherence.


Differential expression of Hdac2 in male and female mice of differing social status.
Mice naturally form social hierarchies, and their experiences as subordinate or dominant mice inform future behavioural strategies. To better understand the neural bases of social dominance, we investigated hippocampal gene and protein expression of histone deacetylase 2 (HDAC2), an epigenetic regulator that decreases expression of synaptic plasticity genes and reduces excitatory synaptic function. Hdac2 in hippocampus was associated with social status. The gene for a closely related histone deacetylase (Hdac1), and HDAC2 protein expression, were not associated with social rank in hippocampus. These findings suggest that Hdac2 expression in hippocampus is distinctly linked with social status.


[First experience with the use of bone marrow stem cells for regeneration therapy of ischemic heart disease.].
To elucidate feasibility of the use of autologous bone marrow stem cells in candidates to myocardial revascularization- patients with ischemic heart disease and cardiosclerosis after myocardial infarction. Between January 2003 and January 2004 25 men aged 56.3+/-5.4 years with ischemic heart disease were subjected to cell therapy including 4 patients with heart failure and 5 - with acute coronary syndrome. Subgroup of patients with postinfarction cardiosclerosis consisted of 16 men satisfying the following criteria: (1) history of myocardial infarction with scar formation; (2) class III-IV angina; (3) presence of indications for endovascular or surgical intervention on coronary arteries. Study protocol included clinical examination, coronary angiography; dobutamine stress-, contrast- and tissue echocardiography with assessment of segmental myocardial perfusion, systolic and diastolic left ventricular function. There were no complications during bone marrow sampling and administration of cells. All patients were restudied 1 month after transplantation. Improvement of clinical state without complications and adverse effects of the procedure noted in all patients was associated with lowering of mean angina class (from 3.4 to 1.4, p<0.05); decrease of NYHA heart failure class (from 3.1 to 1.5); rise of left ventricular ejection fraction (from 42.9 to 56.3%); decrease of average number of asynergic segments (from 5.3+/-0.7 to 2.1+/-0.3, p<0.01). Systolic velocity before intervention was 2.3 cm/s, after procedure in segments subjected to isolated revascularization it increased up to 4.8 cm/s, while in those subjected to revascularization combined with administration of stem cells - up to 6.2 cm/s. Contrast echocardiography in 9 patients demonstrated augmented myocardial perfusion in regions exposed to cell therapy. Transplantation of autologous bone marrow stem cells to ischemic heart disease patients - candidates for myocardial reperfusion - turned out to be safe and well tolerated procedure. Combination of myocardial revascularization with administration of stem cells into regions of postinfarction scars was associated with improvement of total and local myocardial contractility and normalization of left ventricular diastolic filling. Cell therapy facilitated augmentation of myocardial perfusion.


Integration of Patient-reported Outcomes in a Total Joint Arthroplasty Program at a High-volume Academic Medical Center.
Despite widely appreciated barriers to successful clinical implementation, the literature regarding how to operationalize electronic health record-integrated patient-reported outcomes (PROs) remains sparse. We offer a detailed summary of the implementation of PROs into the standard of care at a major tertiary academic medical center. Collection of four Patient-Reported Outcomes Measurement Information System computer adaptive tests was piloted in a large academic orthopaedic surgery ambulatory clinic starting in October 2016. The Patient-Reported Outcomes Measurement Information System computer adaptive tests (Physical Function, Pain Intensity, Pain Interference, and Ability to Return to Social Roles and Activities) were initially implemented as manual order sets to be administered before surgery through 2 years after surgery. Completion rate over time, mean time to completion for all PRO domains, and the overall distribution of symptom severity were used to evaluate the success of the pilot. A subsequent optimization and redesign of the pilot was conducted using tablets, automation of questionnaire deployment, and improved results review to address obstacles encountered during the pilot phase. Two thousand nine distinct joint arthroplasty patients (mean age = 65) completed at least one set of PRO assessments, with overall completion rates reaching 68% and mean completion time of 3 minutes. Focal points during the implementation process included engagement and training of staff, selection of an appropriate patient population and outcome measures, and user friendly data displays for patients and providers. Our pilot program successfully demonstrated that PROs can be administered, scored, and made immediately available within the electronic health record to patients and their providers with minimal disruption of clinical workflows. Although considerable operational and technological challenges remain, we found that the implementation of PROs in clinical care within an ambulatory practice at an academic medical center can be achieved through a constellation of several key factors.


Cucurbitacin E Exerts Anti-Proliferative Activity via Promoting p62-Dependent Apoptosis in Human Non-Small-Cell Lung Cancer A549 Cells.
EGFR tyrosine kinase inhibitors (TKIs) are the first-line treatment for advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, NSCLC patients with wild-type EGFR and KRAS mutation are ineligible for EGFR-TKIs. Therefore, the discovery of new therapeutic agents is urgently needed for NSCLC patients who cannot receive targeted therapies. Natural products possess tremendous chemical diversity and have been extensively investigated for their anticancer activity. In this study, we found that Cucurbitacin E (Cu E), a triterpene of cucurbitacins widely presented in the edible plants of the Cucurbitaceae family, significantly inhibits the viability and proliferation of A549 cells that harbor wild-type EGFR and KRAS mutation. Our results revealed that Cu E increases cell-cycle arrest at G2/M and subG1 phase. Mechanistically, Cu E significantly inhibits the phosphorylation and protein levels of regulatory proteins and hinders G2/M cell-cycle progression. Meanwhile, the treatment of Cu E resulted in DNA damage response and apoptosis. For the first time, we observed that Cu E induces incomplete autophagy as evidenced by increased LC3B-II expression and p62-accumulation. Knockdown of p62 rescued the cells from Cu E-mediated anti-proliferative effect, apoptosis, DNA damage, and ROS production. These findings suggest that Cu E is a promising drug candidate for NSCLC.


Identification of amino acids in p21ras involved in exchange factor interaction.
Through the genetic analysis of vulva development in C. elegans several different sites of mutation have been identified in the let-60 ras protein which have been postulated to affect the function of normal but not oncogenic p21ras (Beitel, G. J., S. G. Clark, and H. R. Horvitz. 1990. Nature 348: 503-509). We have introduced these mutations into mammalian Ha-ras and determined their effect on the function of cellular ras (c-ras), an oncogenically activated variant D12ras and the dominant negative N17ras. From these studies we conclude that two of the mutations S89-->F89 and delta 103-108 destabilise ras when it is in the GDP-bound form. However mutations at A66 and G75 lead to stable proteins on which a ras exchange factor SCD25 is unable to promote the formation of ras-GTP. The mutations at A66 show for the first time that helix alpha 2 of p21ras is involved in the stimulation of guanine nucleotide exchange by exchange factors.


Prevalence of loneliness over ten years among the oldest old.
This study examined the prevalence of loneliness among the oldest old within a 10-year period and studied the influence of various sociodemographic, social and health characteristics on loneliness. The study used population-based data from the Umeå85+/GErontological Regional DAtabase-study (GERDA) for the years 2000-2002, 2005-2007 and 2010-2012 including 85-year-old, 90-year-old and ⩾95-year-old participants. A final sample of 304 participants in 2000-2002, 329 participants in 2005-2007 and 401 participants in 2010-2012 was included in the analyses. Although the level of loneliness was already high in 2000-2002 (49.3% reported frequent loneliness), the results showed limited changes in loneliness during the 10-year study period. Loneliness was closely related to living alone, depressive symptoms and living in institutional settings. Although societal changes such as solitary living and growing urbanization suggest a changing trend in loneliness, we found that the prevalence of loneliness was relatively stable in this study. Nevertheless, loneliness is common among the oldest old and a focus on social issues related to living arrangements and on depressive symptoms is important in understanding loneliness.


Hybrid asexuality as a primary postzygotic barrier between nascent species: On the interconnection between asexuality, hybridization and speciation.
Although sexual reproduction is ubiquitous throughout nature, the molecular machinery behind it has been repeatedly disrupted during evolution, leading to the emergence of asexual lineages in all eukaryotic phyla. Despite intensive research, little is known about what causes the switch from sexual reproduction to asexuality. Interspecific hybridization is one of the candidate explanations, but the reasons for the apparent association between hybridization and asexuality remain unclear. In this study, we combined cross-breeding experiments with population genetic and phylogenomic approaches to reveal the history of speciation and asexuality evolution in European spined loaches (Cobitis). Contemporary species readily hybridize in hybrid zones, but produce infertile males and fertile but clonally reproducing females that cannot mediate introgressions. However, our analysis of exome data indicates that intensive gene flow between species has occurred in the past. Crossings among species with various genetic distances showed that, while distantly related species produced asexual females and sterile males, closely related species produce sexually reproducing hybrids of both sexes. Our results suggest that hybridization leads to sexual hybrids at the initial stages of speciation, but as the species diverge further, the gradual accumulation of reproductive incompatibilities between species could distort their gametogenesis towards asexuality. Interestingly, comparative analysis of published data revealed that hybrid asexuality generally evolves at lower genetic divergences than hybrid sterility or inviability. Given that hybrid asexuality effectively restricts gene flow, it may establish a primary reproductive barrier earlier during diversification than other "classical" forms of postzygotic incompatibilities. Hybrid asexuality may thus indirectly contribute to the speciation process.


The Costs of Indeterminacy: How to Determine Them?
Indeterminate classifiers are cautious models able to predict more than one class in case of high uncertainty. A problem that arises when using such classifiers is how to evaluate their performances. This problem has already been considered in the case where all prediction errors have equivalent costs (that we will refer as the "0/1 costs" or accuracy setting). The purpose of this paper is to study the case of generic cost functions. We provide some properties that the costs of indeterminate predictions could or should follow, and review existing proposals in the light of those properties. This allows us to propose a general formula fitting our properties that can be used to produce and evaluate indeterminate predictions. Some experiments on the cost-sensitive problem of ordinal regression illustrate the behavior of the proposed evaluation criterion.


Ni-induced Changes in Nitrate Assimilation and Antioxidant Metabolism of Verbascum olympicum Boiss.: Could the Plant be Useful for Phytoremediation or/and Restoration Purposes?
Verbascum olympicum Boiss. (Scrophulariaceae) were studied as a candidate plant for remediating the Ni polluted soils. The metabolic responses, such as nitrate assimilation (nitrate reductase and glutamine synthetase activity) and antioxidant system activity [superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity], of this species exposed to nickel in Hoagland's nutrient medium were investigated as remediation performance parameters. The accumulation of nickel and the variations in the content of some elements (B, Cu, Fe, Mg, Mn, Mo and Zn) and some growth parameters, such as the water content, biomass production, and contents of chlorophyll and soluble protein, were also examined. The accumulation of Ni in both the roots and leaves varied depending on the exposure times and doses. Increased oxidative stress was suggested by the increases in the activities of SOD, CAT and APX. Although some element contents were inhibited by Ni treatments, these inhibitory effects was decreased depending on the time, and even these elements are accumulated in roots. These results are the novelties in the use of this species in biotechnology.


Identification of a novel type II classical cadherin: rat cadherin19 is expressed in the cranial ganglia and Schwann cell precursors during development.
To identify a novel type II classical cadherin, we searched the genome database and found rat cadherin19 (cad19) with high similarity to human cadherin19. We also found nucleotide sequences corresponding to rat cad19 in mouse and chicken genomes. In situ hybridization of rat cad19 revealed that rat cad19 mRNA was initially expressed in cephalic neural crest cells, and then in the cranial ganglia, migrating trunk neural crest cells, the nascent dorsal root ganglia, and the sympathetic ganglia. Expression of cad19 overlapped with that of neural crest markers, including Sox10 and AP-2, but cad19 expression was confined to subpopulations of the neural crest-derived cells, those typically observed in the satellite glia at the periphery of the ganglia and Schwann cell precursors along the peripheral nerves. cad19 mRNA was not detected in cells expressing Phox2b, an epibranchial placode-derived neurons, nor in those expressing neuronal markers such as Hu protein. These observations suggest that cad19 is expressed in neural crest-derived, non-neuronal cells. Although the expression of cad19 mRNA persisted in Schwann cell precursors at E14.5, it was no longer detected in maturing Schwann cells at later stages. These results suggest that cad19 is an evolutionarily conserved cadherin and may be involved in the early development of Schwann cells in the peripheral nervous system.


Transcriptomic and bioinformatics analysis of the early time-course of the response to prostaglandin F2 alpha in the bovine corpus luteum.
RNA expression analysis was performed on the corpus luteum tissue at five time points after prostaglandin F2 alpha treatment of midcycle cows using an Affymetrix Bovine Gene v1 Array. The normalized linear microarray data was uploaded to the NCBI GEO repository (GSE94069). Subsequent statistical analysis determined differentially expressed transcripts ± 1.5-fold change from saline control with P ≤ 0.05. Gene ontology of differentially expressed transcripts was annotated by DAVID and Panther. Physiological characteristics of the study animals are presented in a figure. Bioinformatic analysis by Ingenuity Pathway Analysis was curated, compiled, and presented in tables. A dataset comparison with similar microarray analyses was performed and bioinformatics analysis by Ingenuity Pathway Analysis, DAVID, Panther, and String of differentially expressed genes from each dataset as well as the differentially expressed genes common to all three datasets were curated, compiled, and presented in tables. Finally, a table comparing four bioinformatics tools' predictions of functions associated with genes common to all three datasets is presented. These data have been further analyzed and interpreted in the companion article "Early transcriptome responses of the bovine mid-cycle corpus luteum to prostaglandin F2 alpha includes cytokine signaling" [1].


Diffusion models for animals in complex landscapes: incorporating heterogeneity among substrates, individuals and edge behaviours.
1. Animals move commonly through a variety of landscape elements and edges in search of food, mates and other resources. We developed a diffusion model for the movement of an insect herbivore, the planthopper Prokelisia crocea, that inhabits a landscape composed of patches of its host plant, prairie cordgrass Spartina pectinata, embedded in a matrix of mudflat or smooth brome Bromus inermis. 2. We used mark-release-resight experiments to quantify planthopper movements within cordgrass-brome and cordgrass-mudflat arenas. A diffusion model was then fitted that included varying diffusion rates for cordgrass and matrix, edge behaviour in the form of a biased random walk and heterogeneity among planthoppers (sessile vs. mobile). The model parameters were estimated by maximum likelihood using the numerical solution of the diffusion model as a probability density. Akaike's information criterion (AIC) values were used to compare models with different subsets of features. 3. There was clear support for models incorporating edge behaviour and both sessile and mobile insects. The most striking difference between the cordgrass-brome and cordgrass-mudflat experiments involved edge behaviour. Planthoppers crossed the cordgrass-brome edge readily in either direction, but traversed the cordgrass-mudflat edge primarily in one direction (mudflat to cordgrass). Diffusion rates were also significantly higher on mudflat than for cordgrass and brome. 4. The differences in behaviour for cordgrass-brome vs. cordgrass-mudflat edges have implications for the connectivity of cordgrass patches as well as their persistence. Higher dispersal rates are expected between cordgrass patches separated by brome relative to mudflat, but patches surrounded by mudflat appear more likely to persist through time. 5. The experimental design and diffusion models used here could potentially be extended to any organism where mass mark-recapture experiments are feasible, as well as complex natural landscapes.


Acceleration of TDP43 and FUS/TLS protein expressions in the preconditioned hippocampus following repeated transient ischemia.
The 43-kDa transactivation response DNA binding protein (TDP43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), heat shock protein 70 (HSP70), and β-amyloid (Aβ) are induced and involved in cerebral ischemia, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD), but their relationships in ischemic tolerance have never been examined, although they could be involved in endogenous neuroprotection under ischemic preconditioning. In the present study, Mongolian gerbils were subjected to one or three incidents of basically nonlethal 2-min transient common carotid arteries occlusion (tCCAO). Hippocampal CA1 neurons were lost only in the 2-min three times group at 3 and 7 days, which then gradually recovered from 1 to 6 months. Inductions of TDP43 and FUS/TLS were accelerated from 3 months to 7 days or from 7 days to 1 day, respectively, after 2-min three times ischemia compared with once. The cytoplasmic stainings of TDP43 and FUS/TLS showed a further acceleration of the peaks from 1 months to 3 days or from 1 months to 7 days, respectively, after 2-min three times ischemia compared with once. In contrast, HSP70 was induced only at 7 days after 2-min tCCAO for three times, with no expression for Aβ. These data show that ischemic preconditioning offers a way to induce endogenous neuroprotection and neurogenesis in gerbils, with TDP43, FUS/TLS, and HSP70 involved in this function.


Physiological responses to affiliation during conversation: Comparing neurotypical males and males with Asperger syndrome.
We examined the emotional and psychophysiological underpinnings of social interaction in the context of autism spectrum disorder, more specifically, involving participants diagnosed with Asperger syndrome (AS). We recorded participants' autonomic nervous system (ANS) activation (electrodermal activity, heart rate, and heart rate variability) and facial muscle activation during conversations in two different types of male dyads: (1) ten dyads where one participant has been diagnosed with AS (AS/NT dyads) and (2) nine dyads where both participants are neurotypical (NT/NT dyads). Afterwards, three independent raters assessed continuously each participant's affiliative and dominant behaviors during the first and last 10 minutes of the conversations. The relationship between the assessed data and ANS responses was examined. We found that, in the NT/NT dyads, a high level of affiliation displayed by the conversational partner calms down the participant when they are actively dominating the interaction. In contrast, when the participants themselves expressed affiliation, their psychophysiological responses indicated increase in arousal, which suggests that the giving of affiliation is physiologically "hard work." The affiliation-related ANS responses were similar in those NT participants whose conversational partner had AS, while some differences in facial muscle activation did occur in comparison to NT/NT dyads. In the AS participants, in contrast, a high level of affiliation provided by the conversational partner was associated with increase in arousal, suggesting heightened alertness and stress. As for their own affiliative behavior, the AS participants exhibited similar indicators of alertness and stress as the NT participants, but only when their own level of dominance was low. Our results increase understanding of how individuals with AS experience social interaction at the physiological level, and how this experience differs from that in NT individuals. Moreover, our results confirm and further specify our earlier results, where we proposed that affiliation involves the type of "sharing of the burden" that also reverberates in the participants' bodies.


Novel Titanium Nanospike Structure Using Low-Energy Helium Ion Bombardment for the Transgingival Part of a Dental Implant.
The aim of the study was to fabricate a nanospike surface on a titanium alloy surface using a newly established method of low-energy helium ion bombardment. Various methods to achieve nanospike formation on titanium have been introduced recently, and their antibacterial properties have been mainly investigated with respect to Escherichia coli and Staphylococcus aureus. Oral pathogens such as Porphyromonas gingivalis play an important role in the development of peri-implantitis. For that reason, the antibacterial properties of the novel, nanostructured titanium surface against P. gingivalis were assessed, and a possible effect on the viability of gingival fibroblasts was evaluated. Helium sputtering was employed for developing titanium surfaces with nanospikes of 500 nm (ND) in height; commercially available smooth-machined (MD) and sandblasted and acid-etched titanium disks (SLA) were used as controls. Surface structure characterization was performed through scanning electron microscopy (SEM) and atomic force microscopy (AFM). Following incubation with P. gingivalis, antibacterial properties were determined via conventional culturing and SEM. Additionally, the viability of human gingival fibroblasts (HGFs) was tested through MTT assay, and cell morphology was assessed through SEM. SEM images confirmed the successful establishment of a nanospike surface with required heights, albeit with heterogeneity. AFM images of the 500 nm nanospike surface revealed that the roughness is dominated by large-scale hills and valleys. For frame sizes of 5 × 5 μm and smaller, the average roughness is dominated by the height of the titanium spikes. ND successfully induces dysmorphisms within P. gingivalis cultures following the incubation period, while conventional culturing reveals a 17% and 20% reduction for ND compared to MD and SLA, respectively. Moreover, the nanospike surfaces did not affect the viability of human growth fibroblasts despite their sharp surface. This study successfully developed a novel titanium-nanospike-based structuration technique for titanium surfaces. In addition, the nanospikes did not hinder gingival fibroblast viability. Enhanced antimicrobial effects for such a novel nanospike-based resurfacing technique can be achieved through further optimizations for nanospike spacing and height parameters.


Testing the potential of a ribosomal 16S marker for DNA metabarcoding of insects.
Cytochrome c oxidase I (COI) is a powerful marker for DNA barcoding of animals, with good taxonomic resolution and a large reference database. However, when used for DNA metabarcoding, estimation of taxa abundances and species detection are limited due to primer bias caused by highly variable primer binding sites across the COI gene. Therefore, we explored the ability of the 16S ribosomal DNA gene as an alternative metabarcoding marker for species level assessments. Ten bulk samples, each containing equal amounts of tissue from 52 freshwater invertebrate taxa, were sequenced with the Illumina NextSeq 500 system. The 16S primers amplified three more insect species than the Folmer COI primers and amplified more equally, probably due to decreased primer bias. Estimation of biomass might be less biased with 16S than with COI, although variation in read abundances of two orders of magnitudes is still observed. According to these results, the marker choice depends on the scientific question. If the goal is to obtain a taxonomic identification at the species level, then COI is more appropriate due to established reference databases and known taxonomic resolution of this marker, knowing that a greater proportion of insects will be missed using COI Folmer primers. If the goal is to obtain a more comprehensive survey the 16S marker, which requires building a local reference database, or optimised degenerated COI primers could be more appropriate.


Automated Removal of Non-homologous Sequence Stretches with PREQUAL.
Large-scale multigene datasets used in phylogenomics and comparative genomics often contain sequence errors inherited from source genomes and transcriptomes. These errors typically manifest as stretches of non-homologous characters and derive from sequencing, assembly, and/or annotation errors. The lack of automatic tools to detect and remove sequence errors leads to the propagation of these errors in large-scale datasets. PREQUAL is a command line tool that identifies and masks regions with non-homologous adjacent characters in sets of unaligned homologous sequences. PREQUAL uses a full probabilistic approach based on pair hidden Markov models. On the front end, PREQUAL is user-friendly and simple to use while also allowing full customization to adjust filtering sensitivity. It is primarily aimed at amino acid sequences but can handle protein-coding nucleotide sequences. PREQUAL is computationally efficient and shows high sensitivity and accuracy. In this chapter, we briefly introduce the motivation for PREQUAL and its underlying methodology, followed by a description of basic and advanced usage, and conclude with some notes and recommendations. PREQUAL fills an important gap in the current bioinformatics tool kit for phylogenomics, contributing toward increased accuracy and reproducibility in future studies.


Level of Tumor Necrosis Factor Production by Stimulated Blood Mononuclear Cells Can Be Used to Predict Response of Patients With Inflammatory Bowel Diseases to Infliximab.
A substantial proportion patients with inflammatory bowel disease (IBD) have a primary non-response to infliximab; markers are needed to identify patients most likely to respond to treatment. We investigated whether production of tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMCs) can be used as a marker to predict response. We performed a prospective study of 41 adults with IBD (mean age, 38 years; 21 male; 21 with Crohn's disease and 20 with ulcerative colitis) not treated with a biologic agent within the past 6 months; patients were given their first infusion of infliximab at a hospital or clinic in Berlin, Germany. We collected data on clinical scores, levels of C-reactive protein, and ultrasound results (Limberg scores) at baseline (before the first infusion) and after 6 weeks (3rd infliximab infusion). PMBCs were obtained from patients at baseline and 10 healthy individuals (controls) and incubated with lipopolysaccharide. We measured production of cytokines (TNF, interleukin 1 [IL1], IL6, IL8, IL10, IL12p70, and IL22) by ELISA and performed cytometric bead array and flow cytometry analyses. The primary endpoint was clinical response (decrease in Harvey Bradshaw Index scores of 2 or more or decrease in partial Mayo scores of 3 or more at week 6) in patients with PBMCs that produced high vs low levels of TNF. Responders had a shorter median disease duration (P = .018) and higher median Limberg score (P = .021), than nonresponders. Baseline PBMCs from responders produced significantly more TNF (P = .049) and IL6 (P = .028) than from nonresponders; a level of 500 pg/ml TNF identified responders with 82% sensitivity and 78% specificity. In patients with Crohn's disease, this cutoff value (500 pg/ml TNF) identified responders with 100% sensitivity and 82% specificity; TNF levels above this level were independently associated with response to infliximab in multivariate analysis (odds ratio, 16.2; 95% CI, 1.8-148.7; P = .014). The percentage of TNF-positive cells was higher among CD14+ monocytes than lymphocytes after stimulation. Production of a high level of TNF by PBMCs (specifically CD14+ cells) from patients with IBD can identify those most likely to have a clinical response to infliximab therapy. In patients with Crohn's disease, a cutoff value of 500 pg/ml TNF identified responders with 100% sensitivity and 82% specificity.


CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization.
mTOR is a serine/threonine kinase that regulates cell growth, metabolism, proliferation, and survival. mTOR complex-1 (mTORC1) and mTOR complex-2 (mTORC2) are critical mediators of the PI3K-AKT pathway, which is frequently mutated in many cancers, leading to hyperactivation of mTOR signaling. Although rapamycin analogues, allosteric inhibitors that target only the mTORC1 complex, have shown some clinical activity, it is hypothesized that mTOR kinase inhibitors, blocking both mTORC1 and mTORC2 signaling, will have expanded therapeutic potential. Here, we describe the preclinical characterization of CC-223. CC-223 is a potent, selective, and orally bioavailable inhibitor of mTOR kinase, demonstrating inhibition of mTORC1 (pS6RP and p4EBP1) and mTORC2 [pAKT(S473)] in cellular systems. Growth inhibitory activity was demonstrated in hematologic and solid tumor cell lines. mTOR kinase inhibition in cells, by CC-223, resulted in more complete inhibition of the mTOR pathway biomarkers and improved antiproliferative activity as compared with rapamycin. Growth inhibitory activity and apoptosis was demonstrated in a panel of hematologic cancer cell lines. Correlative analysis revealed that IRF4 expression level associates with resistance, whereas mTOR pathway activation seems to associate with sensitivity. Treatment with CC-223 afforded in vivo tumor biomarker inhibition in tumor-bearing mice, after a single oral dose. CC-223 exhibited dose-dependent tumor growth inhibition in multiple solid tumor xenografts. Significant inhibition of mTOR pathway markers pS6RP and pAKT in CC-223-treated tumors suggests that the observed antitumor activity of CC-223 was mediated through inhibition of both mTORC1 and mTORC2. CC-223 is currently in phase I clinical trials.


Oleyl sulfate reveals allosteric inhibition of soybean lipoxygenase-1 and human 15-lipoxygenase.
Inhibition of lipoxygenase (LO) is currently an important goal of biomedical research due to its critical role in asthma, atherosclerosis, and cancer regulation. Steady-state kinetic data indicate that oleic acid (OA) is a simple competitive inhibitor for soybean lipoxygenase; however, kinetic isotope effect (KIE) data suggest a more complicated inhibitory mechanism. To investigate the inhibitory effects of fatty acids on lipoxygenase more thoroughly, we have synthesized a novel inhibitor to lipoxygenase, (Z)-9-octadecenyl sulfate (oleyl sulfate, OS), which imparts kinetic properties that are inconsistent with simple competitive inhibition for both SLO-1 and 15-HLO. The KIE exhibits a hyperbolic rise with addition of OS, indicating the formation of a catalytically active ternary complex with K(D) values of 0.6 +/- 0.2 and 0.4 +/- 0.05 microM for SLO-1 and 15-HLO, respectively. The steady-state kinetics show that SLO-1 proceeds through a hyperbolic mixed-type inhibition pathway, where OS binding (K(i) = 0.7 +/- 0.3 microM) causes an approximate 4-fold increase in the K(m)(app) (alpha = 4.6 +/- 0.5) and a decrease in the k(cat) by approximately 15% (beta = 0.85 +/- 0.1). 15-HLO also exhibits a hyperbolic saturation of k(cat)/K(m) consistent with the observed rise in its KIE. Taken together, these findings indicate the presence of an allosteric site in both SLO-1 and 15-HLO and suggest broad implications regarding the inhibition of LO and the treatment of LO-related diseases.


Natural Tritium Measurements by Ethane Counting.
A method is described for the synthesis of ethane from hydrogen that is at present used for the counting of low-level tritium activity at the La Jolla tritium laboratory. The reaction procedure is simple and involves the mixing of the hydrogen with acetylene over a colloidal palladium catalyst. Counting characteristics of ethane are found to be ideal. With a 1-liter counter filled to three atmospheres of ethane, only a tenfold tritium enrichment is necessary in order to obtain a sensitivity of 0.32 counts per minute per tritium unit.


Risk assessment and perception.
Injury prevention efforts often focus on reducing the risk of potentially dangerous activities, facilities or equipment, such as diving, swimming pools or flotation devices. This paper aims to clarify the concepts of risk assessment and risk perception. Statistically, risk denotes the probability of an untoward event, often expressed in terms of potential financial loss. Subjectively, though, risk denotes an individual's perception of the likelihood and the seriousness of an undesirable event. Individual perception appears to be strongly influenced by personal traits and socio-cultural parameters. Risk assessment helps to form the basis for public health interventions. The implementation and effectiveness of these are influenced by individual risk perception. Therefore, preventive efforts need to incorporate and hopefully influence the determinants of risk perception among the target populations. Considering drowning, both hazard and incidence of submersion injuries are underestimated, whereas treatment options are usually overestimated. Consequently, individual risk alertness needs to be improved--drowning remains a ubiquitous risk.


Risk factors for manipulation under anaesthesia after total knee arthroplasty.
Postoperative range of movement (ROM) is an important measure of successful and satisfying total knee arthroplasty (TKA). Reduced postoperative ROM may be evident in up to 20% of all TKAs and negatively affects satisfaction. To improve ROM, manipulation under anaesthesia (MUA) may be performed. Historically, a limited ROM preoperatively was used as the key harbinger of the postoperative ROM. However, comorbidities may also be useful in predicting postoperative stiffness. The goal was to assess preoperative comorbidities in patients undergoing TKA relative to incidence of postoperative MUA. The hope is to forecast those who may be at increased risk and determine if MUA is an effective form of treatment. Prospectively collected data of TKAs performed at our institution's two hospitals from August 2014 to August 2018 were evaluated for incidence of MUA. Comorbid conditions, risk factors, implant component design and fixation method (cemented vs cementless), and discharge disposition were analyzed. Overall, 3,556 TKAs met the inclusion criteria. Of those, 164 underwent MUA. Patients with increased age and body mass index (BMI) had decreased likelihood of MUA. For every one-year increase in age, the likelihood of MUA decreased by 4%. Similarly, for every one-unit increase in BMI the likelihood of MUA decreased by 6%. There were no differences in incidence of MUA between component type/design or fixation method. Current or former smokers were more likely to have no MUA. Surprisingly, patients discharged to home health service or skilled nursing facility were approximately 40% and 70% less likely than those discharged home with outpatient therapy to be in the MUA group. MUA was effective, with a mean increased ROM of 32.81° (SD 19.85°; -15° to 90°). Younger, thinner patients had highest incidence of MUA. Effect of discharge disposition on rate of MUA was an important finding and may influence surgeons' decisions. Interestingly, use of cement and component design (constraint) did not impact incidence of MUA. Level of Evidence II: Prospective cohort study. Cite this article: Bone Joint J 2020;102-B(6 Supple A):66-72.


Expression and actions of transforming growth factors during human follicular development.
To correlate the temporal expression of transforming growth factor-alpha (TGF-alpha) and TGF-beta genes in granulosa cells (GC) and thecal cells from human follicles at various developmental stages and to determine their trophic effects on GCs. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of extracted RNA from follicular GCs and theca cells. Academic endocrinology laboratory. Premenopausal women undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy for nonovarian reasons. None. Confirmation by the RT-PCR product for TGF-alpha and TGF-beta gene expression in GC and theca cells from human follicles at various developmental stages and (3)H-thymidine uptake in vitro to assess growth effects on GCs. The RT-PCR product indicating the presence of TGF-alpha messenger RNA (mRNA) was found consistently in theca from healthy antral follicles. In theca from large follicles (>1.0 cm) the TGF-alpha PCR product was of reduced intensity. The TGF-alpha was absent or undetectable in granulosa cells from all follicle sizes. The PCR product for TGF-beta was generated by all GC and thecal cell RNAs from all follicle sizes examined. The TGF-alpha promoted and TGF-beta inhibited human GC growth. The presence of TGF-alpha gene expression in thecal cells coincides with periods of follicular growth. The expression of TGF-beta occurs in both cell types throughout antral follicle development. The TGF-alpha and TGF-beta have opposing trophic effects on GCs.


Is There a Role for Preoperative Iron Supplementation in Patients Preparing for a Total Hip or Total Knee Arthroplasty?
Several treatment modalities exist for the treatment of perioperative anemia. We determined the effect of oral iron supplementation on preoperative anemia, and the use of blood-conserving interventions before total hip arthroplasty (THA) and total knee arthroplasty (TKA). A total of 3435 total joint arthroplasties (1461 THAs and 1974 TKAs) were analyzed during 2 phases of a blood conservation program. The first phase used erythropoietin alfa (EPO) or intravenous (IV) iron for patients at risk for perioperative anemia. The second phase included these interventions, as well as preoperative iron supplementation. The effect on preoperative hemoglobin (Hb) and serum ferritin, as well as EPO and IV iron utilization, was determined. Oral iron therapy increased preoperative Hb level by 6 g/L (P < .001) and 7 g/L (P < .001) in the hip and knee cohorts, respectively. Serum ferritin level rose by 80 μg/L (P < .001) and 52 μg/L (P < .001) in the hip and knee cohorts, respectively. The number of patients with an Hb level <130 g/L was significantly reduced (P < .001 for both cohorts), as were patients with serum ferritin levels <35 μg/L (P = .002 for hip and P < .001 for knee cohorts). Utilization of EPO reduced from 16% to 6% (P < .001) and 18% to 6% (P < .001) in the hip and knee cohorts, respectively. Utilization of IV iron reduced from 4% to 2% (P = .05) and 5% to 2% (P < .001) in the hip and knee cohorts, respectively. Oral iron therapy reduced the burden of perioperative anemia and reduced utilization of other blood-conserving therapies before THA and TKA. Future research should delineate the cost-effectiveness of oral iron therapy.


The Harvest Smart PRePTM system versus the Friadent-Schütze platelet-rich plasma kit.
An important reason to improve methods for isolating platelet-rich plasma (PRP) is the potential use of autogenous platelet growth factors. In addition to the Curasan PRP kit (Curasan, Kleinostheim, Germany) and the platelet concentrated collection system (PCCSTM) system, two new methods for the preparation of PRP by the surgeon are now available. This study compared the suitability of these new methods for the preparation of PRP. Whole blood was drawn from 54 healthy donors (33 men and 21 women) aged 23-79 years (38.0 +/- 17.7 years). PRP was prepared from each donor's blood using both the Smart PRePTM system (Harvest Technologies Corporation, Munich, Germany) and the Friadent-Schütze method (PRP kit; Friadent-Schütze, Vienna, Austria). The platelet count in donor whole blood was 276 810 +/- 59 440 /microl. Platelet counts differed significantly between the Smart PRP preparation (1227 890 +/- 312 440 platelets/microl) and the Friadent-Schütze PRP preparation (1440 500 +/- 501 700 platelets/microl) (sign test, P < 0.001). The Smart PRePTM system had a significantly higher collection efficiency (63.4 +/- 7.9%) than the Friadent-Schütze kit (49.6 +/- 13.6%) (sign test, P < 0.001). The leukocyte contents in the two platelet concentrates were similar (Smart PRePTM, 19 261 +/- 8082 platelets/microl; Friadent-Schütze, 21 691 +/- 16 430). Transforming growth factor (TGF)-beta1 and platelet-derived growth factor (PDGF)-AB were higher in the Friadent-Schütze PRP (TGF-beta1, 196.8 +/- 109.6 ng/ml; PDGF-AB, 251.6 +/- 115.4 ng/ml) than in the Smart PRePTM (TGF-beta1, 77.2 +/- 54.8 ng/ml; PDGF-AB, 208 +/- 85.2 ng/ml). The sign test indicated significant differences between the two methods in the concentrations of TGF-beta1 (P < 0.001) and PDGF-AB (P < 0.01). Insulin-like growth factor (IGF)-1 levels in the two PRP preparations were similar (Friadent-Schütze PRP, 72.8 +/- 22.3 ng/ml; Smart PRePTM, 91.4 +/- 21.3 ng/ml). The Smart PRePTM system was superior with respect to ease of handling and preparation time. It also had a significantly higher platelet collection efficiency than the Friadent-Schütze PRePTM kit. The Friadent-Schütze PRP kit offers a slight advantage in the resulting PRP platelet concentration. However, this is easily compensated for in the Smart PRePTM system by reducing the volume of the resulting PRP.


Austro-Asiatic tribes of Northeast India provide hitherto missing genetic link between South and Southeast Asia.
Northeast India, the only region which currently forms a land bridge between the Indian subcontinent and Southeast Asia, has been proposed as an important corridor for the initial peopling of East Asia. Given that the Austro-Asiatic linguistic family is considered to be the oldest and spoken by certain tribes in India, Northeast India and entire Southeast Asia, we expect that populations of this family from Northeast India should provide the signatures of genetic link between Indian and Southeast Asian populations. In order to test this hypothesis, we analyzed mtDNA and Y-Chromosome SNP and STR data of the eight groups of the Austro-Asiatic Khasi from Northeast India and the neighboring Garo and compared with that of other relevant Asian populations. The results suggest that the Austro-Asiatic Khasi tribes of Northeast India represent a genetic continuity between the populations of South and Southeast Asia, thereby advocating that northeast India could have been a major corridor for the movement of populations from India to East/Southeast Asia.


Acid reflux detection and symptom-reflux association using 4-day wireless pH recording combining 48-hour periods off and on PPI therapy.
Studies have shown that extended pH recording improves the sensitivity of esophageal pH monitoring. Controversy exists as to whether pH studies are optimally done off or on proton pump inhibitor (PPI) therapy. The aim of this study was to incorporate periods both off and on PPI therapy in a single, extended pH test and describe the effect of PPI therapy on symptom-reflux associations. Sixty patients underwent 4-day pH recordings using two separate receivers calibrated to a single wireless pH capsule. Patients were off PPI therapy for days 1 and 2. Either rabeprazole 20 mg twice daily or omeprazole/sodium bicarbonate 40 mg twice daily were administered on days 3 and 4. Symptom-reflux correlation was determined by the symptom index (SI), symptom sensitivity index (SSI), and symptom association probability (SAP). Twenty studies were excluded due to premature detachment (9) or incomplete data capture for >6 of the 96-h period (11). Off therapy, 14 patients (35%) had abnormal esophageal acid exposure values. On day 4, 39 patients (98%) had normal acid exposure. The number of symptoms and acid reflux events were significantly higher off PPI therapy. Furthermore, the percentage of patients with a positive SI fell from 50% off PPI to 9% on PPI (P < 0.01), whereas 63% of patients symptomatic off PPI therapy became asymptomatic on PPI therapy and could not have an SI calculated. Similarly, the SAP was abnormal in 45% of patients off PPI therapy but only 10% on PPI therapy (P < 0.01). Extended pH recording improves the detection of abnormal acid reflux and increases the number of recorded symptoms and acid reflux events. Combined off and on PPI therapy pH testing enhances the interpretation of pH monitoring and symptom-reflux correlations, which can be helpful in the management of patients with PPI-unresponsive gastroesophageal acid reflux symptoms.


Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia.
Bone marrow transplantation (BMT) can cure patients with high-risk or recurrent acute lymphoblastic leukemia (ALL). Those lacking a related donor can receive either autologous or histocompatible unrelated donor (URD) marrow. Autotransplantation may result in higher risk of relapse, whereas URD allografts, although associated with serious posttransplant toxicities, may reduce relapse risk. Six years (1987 to 1993) of consecutive autologous BMT (University of Minnesota, Dana Farber Cancer Institute; n = 214) were compared with URD transplants (National Marrow Donor Program; n = 337). Most transplants (70% autologous, 48% URD) were in early remission (first or second complete remission [CR1 or CR2]); 376 patients (75% autologous, 64% URD) were less than 18 years old. Autologous BMT led to significantly lower transplant-related mortality (TRM; relative risk [RR] 0.35; P = .001). URD transplantation offered greater protection against relapse (autologous RR 3.1; P = .001). Patients greater than 18 years old, women, and BMT recipients beyond CR2 had higher TRM, whereas adults, BMT recipients in CR2+, or BMT recipients during 1991 through 1993 had significantly more relapse. After 25 months median follow-up, 100 URD and 56 autologous recipients survive leukemia free. URD BMT in CR2 resulted in superior disease-free survival (DFS), especially for adult patients. Multivariate analysis showed superior DFS for children, men, and BMT during CR1 or 2. Autologous and URD BMT can extend survival for a minority of patients unlikely to be cured by chemotherapy, and the results with either technique are comparable. Greater toxicity and TRM after URD BMT are counterbalanced by better protection against relapse. Prospective studies addressing additional clinical variables are needed to guide clinical decision making about transplant choices for patients with ALL.


Dietary patterns and biochemical markers related to diabetes mellitus: an association analysis based on data from the Study of Cardiovascular Risk in Adolescents (ERICA).
The aim of this study was to investigate the association between dietary patterns and biochemical markers related to diabetes mellitus (DM): glucose, insulin, glycated hemoglobin (HbA1c), and homeostasis model assessment of insulin resistance index from 35 454 Brazilian adolescents 12 to 17 y of age. Dietary patterns were derived using factor analysis by the principal components method. The data originated from the school-based study ERICA (Study of Cardiovascular Risk in Adolescents) carried out between 2013 and 2014. Linear regression models analyzed the associations. Three dietary patterns were found: traditional Brazilian, bread and coffee, and Western. An inverse association was found in young girls between the traditional Brazilian pattern and fasting glucose (β = -0.76; P = 0.005) and HbA1c in the second and third tertiles (β = -0.04; P = 0.002; β = -0 .06; P < 0.001), and the Western pattern with HbA1c (β = -0.02; P = 0.035). In boys, a positive association was found between the second tertile of the dietary pattern and insulin (β = 0.48; P = 0.009) and homeostasis model assessment of insulin resistance index (β = 0.11; P = 0.012). This study showed that the traditional Brazilian pattern was inversely associated with blood glucose and HbA1c values in girls. Furthermore, the data suggest that there is an important difference between boys and girls in the association of dietary patterns and the markers used.


From cognitive targets to symptom reduction: overview of attention and interpretation bias modification research.
Cognitive bias modification (CBM) is a class of mechanised psychological interventions designed to target specific aberrant cognitive processes considered key in the aetiology and/or maintenance of specific psychiatric disorders. In this review, we outline a multistage translational process that allows tracking progress in CBM research. This process involves four steps: (1) the identification of reliable cognitive targets and establishing their association with specific disorders; (2) clinical translations designed to rectify the identified cognitive targets; (3) verification of effective target engagement and (4) testing of clinical utility in randomised controlled trials. Through the prism of this multistage process, we review progress in clinical CBM research in two cognitive domains: attention and interpretation; in six psychiatric conditions: anxiety disorders, major depressive disorder, post-traumatic stress disorder, addictive disorders, eating disorders and obsessive-compulsive disorder. The review highlights achievement as well as shortcomings of the CBM approach en route to becoming a recognised evidence-supported therapy for these disorders.


Slip-sliding away: serial changes and homoplasy in repeat number in the Drosophila yakuba homolog of human cancer susceptibility gene BRCA2.
Several recent studies have examined the function and evolution of a Drosophila homolog to the human breast cancer susceptibility gene BRCA2, named dmbrca2. We previously identified what appeared to be a recent expansion in the RAD51-binding BRC-repeat array in the ancestor of Drosophila yakuba. In this study, we examine patterns of variation and evolution of the dmbrca2 BRC-repeat array within D. yakuba and its close relatives. We develop a model of how unequal crossing over may have produced the expanded form, but we also observe short repeat forms, typical of other species in the D. melanogaster group, segregating within D. yakuba and D. santomea. These short forms do not appear to be identical-by-descent, suggesting that the history of dmbrca2 in the D. melanogaster subgroup has involved repeat unit contractions resulting in homoplasious forms. We conclude that the evolutionary history of dmbrca2 in D. yakuba and perhaps in other Drosophila species may be more complicated than can be inferred from examination of the published single genome sequences per species.


Seneca Valley virus, a systemically deliverable oncolytic picornavirus, and the treatment of neuroendocrine cancers.
Numerous clinical trials have demonstrated that oncolytic viruses can elicit antitumor responses when they are administered directly into localized cancers. However, the treatment of metastatic disease with oncolytic viruses has been challenging due to the inactivation of viruses by components of human blood and/or to inadequate tumor selectivity. We determined the cytolytic potential and selectivity of Seneca Valley Virus-001 (SVV-001), a newly discovered native picornavirus, in neuroendocrine and pediatric tumor cell lines and normal cells. Suitability of the virus for intravenous delivery in humans was assessed by blood inactivation assays. Safety was evaluated in vivo using an immune-competent mouse model, and efficacy was evaluated in vivo in athymic mice bearing tumors derived from human small-cell lung cancer and retinoblastoma cell lines. Cell lines derived from small-cell lung cancers and solid pediatric cancers were at least 10,000-fold more sensitive to the cytolytic activity of SVV-001 than were any of the adult normal human cells tested. Viral infectivity was not inhibited by human blood components. Intravenous doses up to 1 x 10(14) virus particles (vp) per kg were well tolerated, and no dose-limiting toxicity was observed in immune-competent mice. A single intravenous dose of 1 x 10(8) vp per kg into athymic mice bearing preestablished small-cell lung or retinoblastoma tumors resulted in complete, durable responses in ten of ten and five of eight mice, respectively. SVV-001 has potent cytolytic activity and high selectivity for tumor cell lines having neuroendocrine properties versus adult normal cells. Systemically administered SVV-001 has potential for the treatment of metastatic neuroendocrine cancers.


Clinicopathologic and immunohistochemical profile of ovarian metastases from colorectal carcinoma.
Metastasis of colorectal adenocarcinoma of the ovary is not an uncommon occurrence and ovarian metastases from colorectal carcinoma frequently mimic endometrioid and mucinous primary ovarian carcinoma. The clinical and pathologic features of metastatic colorectal adenocarcinoma involving the ovary is reviewed with particular focus on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasm. Immunohistochemical stains that may be useful in the differential diagnosis of metastatic colorectal tumors to the ovary and primary ovarian tumors are detailed.


Role of superoxide anion radicals in microvascular permeability and leukocyte behaviour.
Inflammation is associated with the accumulation and activation of phagocytic cells, such as polymorphonuclear leukocytes, and with the subsequent release and generation of a group of activated oxygen species, some of which are free radicals. These studies were carried out to assess the influence of enzymatically generated free radicals on both microvascular permeability and leukocyte adhesion. The extravasation of fluorescein-labelled dextran mean molecular weight (MW) 150 000 was used to assess microvascular permeability and methodology was developed to measure in vivo leukocyte endothelial interactions. Enzymatically generated superoxide anion radical (O-.2) was associated with an increase in macromolecular extravasation (seen primarily from postcapillary venules) and an increase in leukocyte adhesion. Macromolecular extravasation was found to be dependent on the generation of a hydroxyl radical related interaction while leukocyte adhesion was dependent on the presence of O-.2. It is suggested that the permeability alterations and increased polymorphonuclear leukocyte adhesion seen during inflammation may be partially related to the release of free radicals from inflammatory cells.


Intra- and interspecific social challenges modulate the levels of an androgen precursor in a seasonally territorial tropical damselfish.
Studies on different vertebrate groups have provided evidence that androgen levels in males increase after competitive social interactions during the breeding season, as postulated by the Challenge Hypothesis. However, social modulation of androgen levels may vary with latitude and may differ between species holding seasonal versus year-round territories. Here, we tested the Challenge Hypothesis on a seasonal tropical damselfish, Abudefduf sexfasciatus, where males temporarily defend territory and eggs against both intra- and interspecific individuals. Carrying out simulated territorial intrusions (STIs) in the laboratory, we document for the first time a consistent increase in the plasma level of the androgen precursor 11-ketoandrostenedione (11KA) in fish confronted to either intra- or interspecific challenges. Collecting samples in the field also revealed higher 11KA levels in fish facing frequent territorial interactions than in non-territorial individuals. Levels of 11-ketotestosterone (11KT) were high in territorial males in the field, but were not incremented after simulated territorial intrusions in the laboratory. Plasma levels of cortisol and testosterone were not affected by challenges but were different in wild and captive specimens. Although the endocrine responses to STIs did not differ between intra- and interspecific challenges, agonistic displays expressed by resident fish were more intense towards intraspecific intruders. Taken together, our study emphasizes the need to incorporate androgen precursor concentrations to advance our understanding on the physiology of territorial interactions.


Sonothrombolysis Improves Myocardial Dynamics and Microvascular Obstruction Preventing Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction.
It has recently been demonstrated that high-energy diagnostic transthoracic ultrasound and intravenous microbubbles dissolve thrombi (sonothrombolysis) and increase angiographic recanalization rates in patients with ST-segment-elevation myocardial infarction. We aimed to study the effect of sonothrombolysis on the myocardial dynamics and infarct size obtained by real-time myocardial perfusion echocardiography and their value in preventing left ventricular remodeling. One hundred patients with ST-segment-elevation myocardial infarction were randomized to therapy (50 patients treated with sonothrombolysis and percutaneous coronary intervention) or control (50 patients treated with percutaneous coronary intervention only). Left ventricular volumes, ejection fraction, risk area (before treatment), myocardial perfusion defect over time (infarct size), and global longitudinal strain were determined by quantitative real-time myocardial perfusion echocardiography and speckle tracking echocardiography imaging. Risk area was similar in the control and therapy groups (19.2±10.1% versus 20.7±8.9%; P=0.56) before treatment. The therapy group presented a behavior significantly different than control group over time (P<0.001). The perfusion defect was smaller in the therapy at 48 to 72 hours even in the subgroup of patients with no recanalization at first angiography (12.9±6.5% therapy versus 18.8±9.9% control; P=0.015). The left ventricular global longitudinal strain was higher in the therapy than control immediately after percutaneous coronary intervention (14.1±4.1% versus 12.0±3.3%; P=0.012), and this difference was maintained until 6 months (17.1±3.5% versus 13.6±3.6%; P<0.001). The only predictor of left ventricular remodeling was treatment with sonothrombolysis: the control group was more likely to exhibit left ventricular remodeling with an odds ratio of 2.79 ([95% CI, 0.13-6.86]; P=0.026). Sonothrombolysis reduces microvascular obstruction and improves myocardial dynamics in patients with ST-segment-elevation myocardial infarction and is an independent predictor of left ventricular remodeling over time.


Use of Metaphor as an Explanation Tool in Adverse Childhood Experiences Simulation Training.
Introduction Adverse childhood experiences (ACEs) have profound implications for adult health. Health care practitioners need effective communication tools for trauma-sensitive inquiries with patients. This study aimed to describe characteristics of effective metaphor use by health care trainees when discussing ACEs and health with adult patients, and to provide example metaphors for clinicians to use to sensitively address ACEs. Methods Trainees engaged in a videorecorded simulation as part of a model to teach health care practitioners communication skills related to ACEs. Videos were identified in which the trainee used a metaphor to help explain ACEs during the encounter. Encounter segments that used metaphors were transcribed and metaphor type, duration, and recurrence were coded using a standardized rubric. Each metaphor was scored for effectiveness and basic statistical analysis was conducted. Results Of the 122 videos reviewed, 24 types of metaphors were used, with the most common being the overloaded backpack (n = 24). Mean metaphor duration was 37 s (SD = 24 s). Metaphors rated as effective were shorter and less variable in duration (31.8 s, SD = 14.7 s) than those rated as ineffective (39 s, SD = 34 s). No one metaphor performed significantly better and most of the metaphors were evaluated as being adequate or effective. Conclusion Literary devices like metaphors may be efficient and effective explanatory tools to improve clinician communication skills and patient understanding in addressing sensitive topics, such as ACEs. Minimal time investment is required to employ metaphors in ACEs discussions. The authors found no single metaphor that to be clearly superior, indicating that patient-centered metaphor use may improve communication between clinicians and patients who experienced childhood trauma.


Survivors Achieving Stable Housing: Implementation, Challenges, and Lessons Learned.
There is a movement toward permanent housing as an alternative to emergency shelter for survivors of intimate partner violence (IPV). Through a case study, this article illuminates the challenges survivors encountered at multiple levels after being offered one of 25 permanent housing choice vouchers (HCVs) as part of the Survivors Achieving Stable Housing project. Obtaining an HCV is a complicated and lengthy process; survivors transitioning from emergency shelter may face time limits on shelter stays while awaiting this permanent housing option. This article identifies challenges, such as difficulties with landlords, moving costs, and a lack of affordable housing, similar to issues reported in previous research. However, specific to IPV survivors, intersecting U.S. Department of Housing and Urban Development and Violence Against Women Reauthorization Act of 2013 (S. 47) policies led to challenges in implementing and interpreting rules and guidance for IPV survivors. Survivor safety from an abusive partner and across other aspects of their lives is of particular concern to survivors as they consider housing options. Given the overlap of homelessness and IPV, social workers in both systems must be knowledgeable about the intersecting issues survivors face as well as the policies affecting them so they can advocate effectively for their clients.


Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells.
Interendothelial junctions play an important role in the regulation of endothelial functions, such as vasculogenesis, angiogenesis, and vascular permeability. In this paper we show that vascular endothelial growth factor (VEGF), a potent inducer of new blood vessels and vascular permeability in vivo, stimulated the migration of endothelial cells after artificial monolayer wounding and induced an increase in paracellular permeability of human umbilical vein endothelial cells (HUVECs). Furthermore, VEGF increased phosphotyrosine labeling at cell-cell contacts. Biochemical analyses revealed a strong induction of VEGF-receptor-2 (flk-1/KDR) tyrosine-autophosphorylation by VEGF which was maximal after 5 minutes and was followed by receptor downregulation. 15 minutes to 1 hour after VEGF stimulation the endothelial adherens junction components VE-cadherin, beta-catenin, plakoglobin, and p120 were maximally phosphorylated on tyrosine, while alpha-catenin was not modified. PECAM-1/CD31, another cell-cell junctional adhesive molecule, was tyrosine phosphorylated with similar kinetics in response to VEGF. In contrast, activation of VEGF-receptor-1 (Flt-1) by its specific ligand placenta growth factor (PlGF) had no effect on the tyrosine phosphorylation of cadherins and catenins. Despite the rapid and transient receptor activation and the subsequent tyrosine phosphorylation of adherens junction proteins the cadherin complex remained stable and associated with junctions. Our results demonstrate that the endothelial adherens junction is a downstream target of VEGFR-2 signaling and suggest that tyrosine phosphorylation of its components may be involved in the the loosening of cell-cell contacts in established vessels to modulate transendothelial permeability and to allow sprouting and cell migration during angiogenesis.


Using the computer to understand the chemistry of conical intersections.
The application of computational chemistry in resolving photochemical and photobiological problems depends on theoretical models and calculation strategies that allow an understanding of how and when the energy contained in a photon can be used or dissipated by a molecule. Progress in this arena has been the result of a scientific journey that can be traced from the 1960s and 1970s with the development of the concept of the "photochemical funnel", and again from the 1980s and 1990s with the development and application of ab initio multiconfigurational quantum chemistry. Mainly following the viewpoint and contributions of the corresponding author (together with others), here we show that both the early and the ongoing research points to a central role of conical intersections in the molecular-level control of the selectivity and efficiency of photochemical reactions and internal conversion processes.


X-domain of peptide synthetases recruits oxygenases crucial for glycopeptide biosynthesis.
Non-ribosomal peptide synthetase (NRPS) mega-enzyme complexes are modular assembly lines that are involved in the biosynthesis of numerous peptide metabolites independently of the ribosome. The multiple interactions between catalytic domains within the NRPS machinery are further complemented by additional interactions with external enzymes, particularly focused on the final peptide maturation process. An important class of NRPS metabolites that require extensive external modification of the NRPS-bound peptide are the glycopeptide antibiotics (GPAs), which include vancomycin and teicoplanin. These clinically relevant peptide antibiotics undergo cytochrome P450-catalysed oxidative crosslinking of aromatic side chains to achieve their final, active conformation. However, the mechanism underlying the recruitment of the cytochrome P450 oxygenases to the NRPS-bound peptide was previously unknown. Here we show, through in vitro studies, that the X-domain, a conserved domain of unknown function present in the final module of all GPA NRPS machineries, is responsible for the recruitment of oxygenases to the NRPS-bound peptide to perform the essential side-chain crosslinking. X-ray crystallography shows that the X-domain is structurally related to condensation domains, but that its amino acid substitutions render it catalytically inactive. We found that the X-domain recruits cytochrome P450 oxygenases to the NRPS and determined the interface by solving the structure of a P450-X-domain complex. Additionally, we demonstrated that the modification of peptide precursors by oxygenases in vitro--in particular the installation of the second crosslink in GPA biosynthesis--occurs only in the presence of the X-domain. Our results indicate that the presentation of peptidyl carrier protein (PCP)-bound substrates for oxidation in GPA biosynthesis requires the presence of the NRPS X-domain to ensure conversion of the precursor peptide into a mature aglycone, and that the carrier protein domain alone is not always sufficient to generate a competent substrate for external cytochrome P450 oxygenases.


High ESBL-E colonization rate among children in Gabon: a follow-up study.
A previous study conducted in Gabon, Central Africa, in 2010/11 found a high colonization rate with extended-spectrum β-lactamase-producing enterobacterales (ESBL-E) among children of ~34 %. Eight years later, we aimed to reassess the ESBL-E rate and previously identified risk factors for colonization in children from Gabon. We conducted a cross-sectional cohort study in 2018 on 92 outpatients under 5 years of age with diarrhoea in Lambaréné, Gabon, in whom a rectal swab was obtained at the initial medical encounter (baseline). Fifty-eight of these provided a further rectal swab 1 week afterwards. ESBL-E colonization was assessed [following the European Committee on Antimicrobial Susceptibility Testing (EUCAST)], and in confirmed ESBL-E isolates the susceptibility to meropenem and the prevalence of the most abundant ESBL genes, bla CTX-M, bla SHV, and bla TEM, were investigated. At baseline, the ESBL-E colonization rate was 57 % (52/92; 95 % CI: 46-67). Hospitalization during the previous year, chicken consumption in the past week and young age were identified as independent risk factors for ESBL-E colonization at baseline. On day 7, the ESBL-E carriage rate was 72 % (42/58; 95 % CI: 59-83). All ESBL-E isolates (n=293) were susceptible to meropenem and bla CTX-M was the most frequently detected β-lactamase gene. The ESBL-E colonization rate among children from Gabon is alarmingly high, with indications of further increase over recent years. While all ESBL-E strains remain currently susceptible to meropenem, in practice no adequate treatment is available locally for severe infections with such isolates. It is thus of the utmost importance to invest in improved hospital infection prevention and control measures to combat ESBL-E effectively.


Management development and change in a demanding health care environment.
The problems facing many US health care organizations may prove critical for survival for many of them. Outlines the nature of the problems: increased patient demand, tensions among personnel, technological innovation, cost-conscious purchasers of care, the need to improve cost-efficiency, and barriers to change within organizations. This last presents a number of problems that may often seem intractable and are peculiar to this type of organization.


Transient expressive (nonfluent) dysphasia after metrizamide myelography.
Four (3.4%) of 117 patients undergoing metrizamide myelography experienced transient expressive dysphasia 7-8 hr after myelography and lasting up to 36 hr. All four patients had lumbar myelograms obtained with 15 ml of 190 mg l/ml (2850 mg l). Metrizamide was injected via lumbar puncture with a 20 gauge spinal needle under fluoroscopic control. Neurologic complications after metrizamide have been reported, but so far have appeared to be transient. It is likely that the transient expressive dysphasia experienced by the four patients reported here was a neurotoxic reaction, rather than a seizure phenomenon.


Cervimetry: a review of methods for measuring cervical dilatation during labor.
Several different methods of measuring cervical dilatation have been described. In this article, we review those methods and examine findings from studies using them. Although many instruments have been developed to measure cervical dilatation during labor and their use as a research tool has been established, no device has yet been successfully used for clinical obstetrics. The ideal device has not yet been developed; however, because repeated digital cervical examinations are time consuming for the clinician, are poorly reproducible, and are uncomfortable for the patient, continued efforts to develop a cervimeter suitable for clinical use is a worthwhile endeavor.


Dense Swin Transformer for Classification of Thyroid Nodules.
As an early sign of thyroid cancer, thyroid nodules are the most common nodular lesions. As a non-invasive imaging method, ultrasound is widely used in the diagnosis of benign and malignant thyroid nodules. As there is no obvious difference in appearance between the two types of thyroid nodules, and the contrast with the surrounding muscle tissue is too low, it is difficult to distinguish the benign and malignant nodules. Therefore, a dense nodal Swin-Transformer(DST) method for the diagnosis of thyroid nodules is proposed in this paper. Image segmentation is carried out through patch, and feature maps of different sizes are constructed in four stages, which consider different information of each layer of features. In each stage block, a dense connection mechanism is used to make full use of multi-layer features and effectively improve the diagnostic performance. The experimental results of multi-center ultrasound data collected from 17 hospitals show that the accuracy of the proposed method is 87.27%, the sensitivity is 88.63%, and the specific effect is 85.16%, which verifies that the proposed algorithm has the potential to assist clinical practice.


Baller-Gerold syndrome associated with dextrocardia.
Baller-Gerold Syndrome (BGS) is a rare autosomal recessive disorder that is apparent at birth. The disorder is characterized by distinctive malformations of the skull and facial area and bones of the forearms and hands. We report a 4 year old boy in whom the clinical features of craniosynostosis and bilateral absent thumbs and radii led to a diagnosis of Baller-Gerold syndrome. Physical examination revealed that the heart was localized to the right side. Echocardiography confirmed dextrocardia. Dextrocardia has not previously been reported with Baller-Gerold syndrome. To the best of our knowledge, this is the first reported case of Baller-Gerold syndrome associated with dextrocardia.


[Role of the somatic monoaminergic systems in the mechanisms of regulation of pain sensitivity during reflex stimulation].
Experiments on rats were performed to study the role of the monoaminergic systems in the mechanisms of analgesia produced by stress (foot shock) and auricular electroacupuncture (AEA). Analgesia was measured by the hot-plate (HP) and the tail-flick (TF) tests. Inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine (alpha-MPT) antagonized the AEA-induced analgesia measured by the TF test. alpha-MPT did not influence the HP test latency after AEA, and HP or TF tests after stress. Inhibition of dopamine receptors by haloperidol produced a decrease in the stress- and AEA-induced analgesia. The similar effects were demonstrated in propranolol treated rats after AEA. P-chlorophenylalanine (an inhibitor of serotonin synthesis) suppressed the stress-induced analgesia measured by the HP test and AEA-induced analgesia measured by the HP or TF tests. The data indicate that the monoaminergic systems are involved in the stress- and AEA-induced analgesia. Apart from the monoaminergic systems, other neurochemical mechanisms are also involved in the stress- and AEA-induced analgesia.


Comparison of Risk Factors in Patients With Acute and Chronic Orofacial Pain.
Management of patients with orofacial pain may benefit from a better understanding about patient factors that may lead pain chronicity. In this study, we retrospectively compared physical and psychological factors in patients with acute and chronic orofacial pain. We analyzed data from 854 patients presenting to the Orofacial Pain Center, Department of Dental Anesthesiology, Tokyo Dental College, Suidobashi Hospital between April 2010 and March 2014. We categorized patients into the acute group if their condition had persisted <6 months and the chronic group if their condition had lasted 6 months or longer, based on the classification by the International Association for the Study of Pain. The retrospective data were analyzed by using univariate analysis on background factors from a health questionnaire, pain evaluation sheet, and psychological test completed at the time of presentation. Multiple logistic regression was applied on these factors. Our results suggest that female gender and high trait anxiety may be involved in orofacial pain becoming chronic.


Small RNAs establish delays and temporal thresholds in gene expression.
Noncoding RNAs are crucial regulators of gene expression in prokaryotes and eukaryotes, but how they affect the dynamics of transcriptional networks remains poorly understood. We analyzed the temporal characteristics of the cyanobacterial iron stress response by mathematical modeling and quantitative experimental analyses and focused on the role of a recently discovered small noncoding RNA, IsrR. We found that IsrR is responsible for a pronounced delay in the accumulation of isiA mRNA encoding the late-phase stress protein, IsiA, and that it ensures a rapid decline in isiA levels once external stress triggers are removed. These kinetic properties allow the system to selectively respond to sustained (as opposed to transient) stimuli and thus establish a temporal threshold, which prevents energetically costly IsiA accumulation under short-term stress conditions. Biological information is frequently encoded in the quantitative aspects of intracellular signals (e.g., amplitude and duration). Our simulations reveal that competitive inhibition and regulated degradation allow intracellular regulatory networks to efficiently discriminate between transient and sustained inputs.


Unoccluded retinol penetrates human skin in vivo more effectively than unoccluded retinyl palmitate or retinoic acid.
The formation of all-trans retinoic acid is an oxidative process whereby retinol is converted to retinaldehyde and then to retinoic acid. Because retinol causes qualitative molecular changes similar to those produced by retinoic acid, we compared potency of retinol, retinaldehyde, and retinyl palmitate to retinoic acid and assessed the effects of occlusion. Retinoids were prepared in an experimental vehicle of 95% ethanol:propylene glycol (7:3) with anti-oxidant. Induction of retinoic acid 4-hydroxylase activity was the end point for comparison. Retinoic acid concentrations from 0.001% to 0.05% under occlusion produced a linear dose-response induction of 4-hydroxylase activity. The concentrations of the other retinoids under occlusion required to achieve significant induction of enzyme activity were 0.6% retinyl palmitate, 0.025% retinol, and 0.01% retinaldehyde. The linear dose-response was lost with retinoid concentrations in excess of 0.25% retinol or 0.5% retinaldehyde. Statistical analyses showed no difference in 4-hydroxylase activity between unoccluded and occluded retinol treated sites. By contrast, however, unoccluded sites treated with retinoic acid or retinyl palmitate had less induction of 4-hydroxylase activity than occluded sites. Retinol, retinaldehyde, and retinyl palmitate did not produce erythema but did increase epidermal thickness. Although retinol is a weaker retinoid than retinoic acid, the increased penetration of unoccluded retinol in comparison to unoccluded retinoic acid with this prototypic vehicle confers on retinol a more effective delivery of a retinoidal effect than unoccluded retinoic acid. Retinol at 0.25% may be a useful retinoid for application without occlusion because it does not irritate but does induce cellular and molecular changes similar to those observed with application of 0.025% retinoic acid.


Perceptions of Alcohol Advertising Vary Based on Psychological Characteristics.
The alcohol industry recognizes children and pregnant women as population sub-groups vulnerable to the effects of alcohol marketing. Research indicates that heavy alcohol users are also potentially vulnerable to alcohol marketing. The purpose of the current study is to determine if sub-groups defined by psychological characteristics should be classified as potentially vulnerable as well. College students (n = 326) from two northeast schools were recruited to complete a survey containing questions on demographics, alcohol use, and psychological characteristics (alcohol expectancies, alcohol dependence, sensation seeking traits, and past delinquent behaviors). Additionally, after viewing each of five alcohol ads (4 television and 1 magazine), participants answered questions about their perceptions of alcohol consumption, responsible drinking, excessive drinking, and appeal of the ads. Main effects were assessed using hierarchical linear modeling, with adjustment for age, sex, race, ethnicity, and AUDIT score. Alcohol expectancies (p < .001), particularly the social and physical pleasure and social expressiveness sub-scales, and sensation seeking traits (p = .002) were positively associated with alcohol ad appeal. Alcohol dependence symptoms, specifically impaired control and tolerance, were positively associated with perceptions of responsible drinking (p = .035), even though mean perceived number of drinks consumed met the definition of binge drinking. Individuals with positive alcohol expectancies, sensation seeking traits, and alcohol dependence may be vulnerable to alcohol advertising and marketing. Because alcohol advertising often contains content that can serve as a cue or reinforce to drink, specific regulations may be needed to prevent alcohol-related harm from occurring in these sub-populations.


Human fetal brain antigen expression common to tumors of neuroectodermal tissue origin.
The antigenic relationship between human tumors of neuroectodermal origin and fetal brain were further investigated by characterization of two hybridoma antibodies derived from a fusion of P3-NS1/1-Ag 4-1 (NSI) myeloma cells and splenocytes hyperimmunized to second trimester human fetal brain homogenate. Monoclonal antibodies (MAs) 1H8cl 2 and 1H8cl 3 were analyzed by cell surface radioimmunoassay (CS-RIA), quantitative absorption, indirect immunofluorescence, and peroxidase-antiperoxidase (PAP) immunohistology. MA 1H8cl 3 is the more broadly reactive, binding to 9/14 glioblastoma (GBM), 2/3 neuroblastoma, 1/2 melanoma, and 1 medulloblastoma cell line(s) by CS-RIA analysis, and to 12/15 GBM, fetal brain, spleen, and liver, and adult spleen by PAP analysis. MA 1H8cl 2 is more restricted, binding to 7/14 GBM, 2/3 neuroblastoma, 1 medulloblastoma, and 2/3 fetal skin fibroblast cell line(s) by CS-RIA, and to 9/15 GBM and fetal brain and spleen by PAP analysis. Control non-central nervous system tumors and normal adult tissue including brain, thymus, lymph node, liver, kidney, lung, skin, and pancreas, were unreactive with both 1H8cl 2 and 1H8cl 3 by CS-RIA, PAP, and absorption analysis. The data presented here establish the unique nature of the detected antigenic specificities as compared to previously described oncofetal and onconeural antigens, and define two immune reagents which are operationally specific for tumors of neuroectodermal origin within the adult central nervous system.


Impact of Water Coadsorption on the Electrode Potential of H-Pt(1 1 1)-Liquid Water Interfaces.
Density functional theory molecular dynamics simulations of H-covered Pt(111)-H_{2}O interfaces reveal that, in contrast to common understanding, H_{2}O coadsorption has a significant impact on the electrode potential of and plays a major role in determining the stability of H adsorbates under electrochemical conditions. Based on these insights, we explain the origin behind the experimentally observed upper limit of H coverage well below one monolayer and derive a chemically intuitive model for metal-water bonding that explains an unexpectedly large interaction between coadsorbed water and adsorbates.


Airway management success and hypoxemia rates in air and ground critical care transport: a prospective multicenter study.
To assess critical care transport (CCT) crews' endotracheal intubation (ETI) attempts, success rates, and peri-ETI oxygenation. Participants were adult and pediatric patients undergoing attempted advanced airway management during the period from July 2007 to December 2008 by crews from 11 CCT programs varying in geography, crew configuration, and casemix; all crews had access to neuromuscular-blocking agents. Data collected included airway management variables defined per national consensus criteria. Descriptive analysis focused on ETI success rates (reported with exact binomial 95% confidence intervals [CIs]) and occurrence of new hypoxemia (oxygen saturation [SpO(2)] dropping below 90% during or after ETI); to assess categorical variables, Fisher's exact test, Pearson chi(2), and logistic regression were employed to explore associations between predictor variables and ETI failure or new hypoxemia. For all tests, p < 0.05 defined significance. There were 603 total attempts at airway management, with successful oral or nasal ETI in 582 cases, or 96.5% (95% CI 94.7-97.8%). In 182 cases (30.2%, 95% CI 26.5-34.0%), there were failed ETI attempts prior to CCT crew arrival; CCT crew ETI success on these patients (96.2%, 95% CI 92.2-98.4%) was just as high as in the patients in whom there was no pre-CCT ETI attempt (p = 0.81). New hypoxemia occurred in only six cases (1.6% of the 365 cases with ongoing SpO(2) monitoring; 95% CI 0.6-3.5%); the only predictor of new hypoxemia was pre-ETI hypotension (p < 0.001). A requirement for multiple ETI attempts by CCT crews was not associated with new hypoxemia (Fisher's exact p = 0.13). CCT crews' ETI success rates were very high, and even when ETI required multiple attempts, airway management was rarely associated with SpO(2) derangement. CCT crews' ETI success rates were equally high in the subset of patients in whom ground emergency medical services (EMS) ETI failed prior to arrival of transport crews.


Characterization, mechanical, and antibacterial properties of nanofibers derived from olive leaf, fumitory, and terebinth extracts.
In this study, nanofiber structures were obtained with convenient polymers (PVA [polyvinyl alcohol] and PCL [poly o-caprolactone]) derived from the herbal extracts of olive leaves, fumitory, and terebinth plants. Optimum nanofiber structures were identified by measuring viscosity and conductivity values and performing morphological analysis, characterization, and mechanical tests of the prepared solutions. The potential use for wound healing at the most efficient level was determined as a result of antibacterial analysis of the structures obtained. APT (PVA/terebinth) and BFO (PCL/fumitory) nanofibers had the thinnest diameter range and the highest strength values. In terms of the determination of antibacterial effects, nanofiber structures of all 3 plant species proved to be effective against bacteria. The greatest effect was observed against Escherichia coli in the nanofiber structure containing olive leaves, with a zone diameter of 32 mm. In addition, APT and BFO nanofibers had the highest values of thinness and strength. In these 2 samples, using BFO against Staphylococcus aureus and APT against Candida albicans increased their areas of activity. In the literature review, no study was available about obtaining nanofibers, especially from fumitory and terebinth plants. This study aimed to increase knowledge on obtaining nanofiber structures, including various polymers derived from olive leaves, fumitory, and terebinth plants.