Application of bluetongue Disabled Infectious Single Animal (DISA) vaccine for different serotypes by VP2 exchange or incorporation of chimeric VP2.
Bluetongue is a disease of ruminants caused by the bluetongue virus (BTV). Bluetongue outbreaks can be controlled by vaccination, however, currently available vaccines have several drawbacks. Further, there are at least 26 BTV serotypes, with low cross protection. A next-generation vaccine based on live-attenuated BTV without expression of non-structural proteins NS3/NS3a, named Disabled Infectious Single Animal (DISA) vaccine, was recently developed for serotype 8 by exchange of the serotype determining outer capsid protein VP2. DISA vaccines are replicating vaccines but do not cause detectable viremia, and induce serotype specific protection. Here, we exchanged VP2 of laboratory strain BTV1 for VP2 of European serotypes 2, 4, 8 and 9 using reverse genetics, without observing large effects on virus growth. Exchange of VP2 from serotype 16 and 25 was however not possible. Therefore, chimeric VP2 proteins of BTV1 containing possible immunogenic regions of these serotypes were studied. BTV1, expressing 1/16 chimeric VP2 proteins was functional in virus replication in vitro and contained neutralizing epitopes of both serotype 1 and 16. For serotype 25 this approach failed. We combined VP2 exchange with the NS3/NS3a negative phenotype in BTV1 as previously described for serotype 8 DISA vaccine. DISA vaccine with 1/16 chimeric VP2 containing amino acid region 249-398 of serotype 16 raised antibodies in sheep neutralizing both BTV1 and BTV16. This suggests that DISA vaccine could be protective for both parental serotypes present in chimeric VP2. We here demonstrate the application of the BT DISA vaccine platform for several serotypes and further extend the application for serotypes that are unsuccessful in single VP2 exchange.


Is the Wellness Recovery Action Plan (WRAP) efficacious for improving personal and clinical recovery outcomes? A systematic review and meta-analysis.
The Wellness Recovery Action Plan (WRAP) is a structured approach to illness self-management that is widely used within mental health services. This systematic review identifies, appraises, and meta-analyzes quantitative evidence from experimental or quasi-experimental comparison group designs for effects of WRAP on measures reflecting personal recovery and clinical symptomatology. A systematic strategy was used to search 6 electronic reference databases (Medline, CINAHL, EMBASE, PsycINFO, PsycARTICLES, The Cochrane Library) using full-text, keywords, and Medical Subject Headings (MeSh)/Thesaurus headings terms. Unpublished research was identified using the same strategy in the EThOS database. Controlled trials of WRAP were selected and assessed for quality. Meta-analyses were applied to quantitative data to establish the effects of WRAP on outcomes of interest. Of 253 studies initially identified, 5 quantitative studies (reported in 6 papers) reporting controlled trials were included in the review. Meta-analyses revealed that, relative to inactive control conditions, WRAP was (a) superior for promoting self-perceived recovery outcomes (demonstrating a small-but-significant pooled effect), but (b) not superior for reducing clinical symptomatology-although restriction to randomized-controlled trials revealed 1 small effect favoring WRAP for reducing depression. Participation in WRAP has positive outcomes for participants, quantifiable using comprehensive measures of self-perceived recovery. Improvements were not sustained over time. Future research could explore this, as well as potential effects of follow-up WRAP sessions. The results support a move to broader measurement of outcomes within mental health, away from a reliance on clinical outcome measures. Recommendations for further research are made. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Adverse perinatal outcomes associated with antiretroviral therapy regimens: systematic review and network meta-analysis.
Assess adverse perinatal outcomes associated with antenatal antiretroviral therapy (ART) regimens. Systematic review and network meta-analysis of randomized controlled trials (RCTS). We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, EMBASE, and the Cochrane Central Register of Controlled Trials and four clinical trial databases from 1 January 1980 to 28 April 2018. We included RCTs of antenatal ART regimens in HIV-positive pregnant women, which assessed preterm birth (PTB), spontaneous preterm birth (sPTB), very preterm birth (VPTB), low birthweight (LBW), very low birthweight (VLBW), small-for-gestational-age (SGA), neonatal death (NND), and mother-to-child-transmission. We used random-effects network meta-analysis models to calculate relative risks for treatment comparisons and the hierarchy of treatments. Of 83 260 citations identified, 10 manuscripts were included, assessing 6285 women. Compared with zidovudine (ZDV) monotherapy, we found a higher risk of LBW after exposure to zidovudine/lamivudine/efavirenz (ZDV/3TC/EFV; relative risk 1.61; 95% CI 1.03-2.51), tenofovir disoproxil fumarate/emtricitabine/ritonavir-boosted lopinavir (TDF/FTC/LPV/r; 1.64; 1.18-2.29), or zidovudine/lamivudine/ritonavir-boosted lopinavir (ZDV/3TC/LPV/r; 1.87; 1.58-2.20). TDF/FTC/LPV/r carried an increased risk of VLBW, compared with ZDV monotherapy (5.40; 1.08-27.08). ZDV/3TC/LPV/r posed a higher risk of PTB than ZDV monotherapy (1.43; 1.08-1.91) and a higher risk of sPTB than zidovudine/lamivudine/abacavir (ZDV/3TC/ABC) (1.81; 1.21-2.71). LPV/r-containing regimens also carried the highest risks of VPTB, SGA and NND, although the limited data showed no significant differences. Of the ART regimens assessed in RCTs in pregnancy, LPV/r-containing regimens were associated with the highest risks of adverse perinatal outcomes.


Biogas Production from Brewer's Yeast Using an Anaerobic Sequencing Batch Reactor.
Renewable energy sources are becoming increasingly important in the beverage and food industries. In the brewing industry, a significant percentage of the used raw materials finishes the process as secondary resource or waste. The research on the anaerobic digestion of brewer's yeast has been scarce until recent years. One of the reasons for this is its use as a secondary resource in the food industry and as cattle feed. Additionally, market value of brewer's yeast is higher than its energy value. Due to the increase of energy prices, brewer's yeast has become of interest as energy substrate despite its difficult degradability in anaerobic conditions. The anaerobic co-digestion of brewer's yeast and anaerobically treated brewery wastewater was studied using a pilot-scale anaerobic sequencing batch reactor (ASBR) seeded with granular biomass. The experiments showed very good and stable operation with an organic loading rate of up to 8.0 kg/(m3·day), and with a maximum achieved organic loading rate of 13.6 kg/(m3·day) in a single cycle. A specific biogas productivity of over 0.430 m3/kg of the total chemical oxygen demand (COD) inserted, and total COD removal efficiencies of over 90% were achieved. This study suggests that the brewer's yeast can be successfully digested in an ASBR without adverse effects on the biogas production from brewer's yeast/wastewater mixtures of up to 8% (by volume). By using the brewer's yeast in the ASBR process, the biogas production from brewery wastewater could be increased by 50%.


Adaptation to cesarean birth: implementation of an international multisite study.
The purpose of this column is to describe the implementation of an international multisite Roy adaptation model-based study of women's perceptions of and responses to cesarean birth. The need for the study arose from the concern that women's childbearing needs may not be met to their full satisfaction, especially if the infant is born by cesarean. Serendipity and networking played a part in the selection of four study sites in the United States (Boston, Milwaukee, Norfolk, Oklahoma City) and two in other countries (Finland, Australia). Data were collected by nursing students and staff nurses. Post-hoc consideration of the diversity of study sites revealed opportunities for examination of the influence of the contextual stimuli of culture and geographic region on the women's adaptation to cesarean birth. Strategies used to foster integration of teaching, practice, and research are discussed.


Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy.
Colony stimulating factor 1 (CSF-1) recruits tumor-infiltrating myeloid cells (TIM) that suppress tumor immunity, including M2 macrophages and myeloid-derived suppressor cells (MDSC). The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397. In this study, we used a syngeneic mouse model of BRAF(V600E)-driven melanoma to evaluate the ability of PLX3397 to improve the efficacy of adoptive cell therapy (ACT). In this model, we found that combined treatment produced superior antitumor responses compared with single treatments. In mice receiving the combined treatment, a dramatic reduction of TIMs and a skewing of MHCII(low) to MHCII(hi) macrophages were observed. Furthermore, mice receiving the combined treatment exhibited an increase in tumor-infiltrating lymphocytes (TIL) and T cells, as revealed by real-time imaging in vivo. In support of these observations, TILs from these mice released higher levels of IFN-γ. In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.


Arthroscopic lavage and debridement for osteoarthritis of the knee: an evidence-based analysis.
The purpose of this review was to determine the effectiveness and adverse effects of arthroscopic lavage and debridement, with or without lavage, in the treatment of symptoms of osteoarthritis (OA) of the knee, and to conduct an economic analysis if evidence for effectiveness can be established. QUESTIONS ASKED: Does arthroscopic lavage improve motor function and pain associated with OA of the knee?Does arthroscopic debridement improve motor function and pain associated with OA of the knee?If evidence for effectiveness can be established, what is the duration of effect?What are the adverse effects of these procedures?What are the economic considerations if evidence for effectiveness can be established? Osteoarthritis, the most common rheumatologic musculoskeletal disorder, affects about 10% of the Canadian adult population. Although the natural history of OA is not known, it is a degenerative condition that affects the bone cartilage in the joint. It can be diagnosed at earlier ages, particularly within the sports injuries population, though the prevalence of non-injury-related OA increases with increasing age and varies with gender, with women being twice as likely as men to be diagnosed with this condition. Thus, with an aging population, the impact of OA on the health care system is expected to be considerable. Treatments for OA of the knee include conservative or nonpharmacological therapy, like physiotherapy, weight management and exercise; and more generally, intra-articular injections, arthroscopic surgery and knee replacement surgery. Whereas knee replacement surgery is considered an end-of-line intervention, the less invasive surgical procedures of lavage or debridement may be recommended for earlier and more severe disease. Both arthroscopic lavage and debridement are generally indicated in patients with knee joint pain, with or without mechanical problems, that are refractory to medical therapy. The clinical utility of these procedures is unclear, hence, the assessment of their effectiveness in this review. LAVAGE AND DEBRIDEMENT: Arthroscopic lavage involves the visually guided introduction of saline solution into the knee joint and removal of fluid, with the intent of extracting any excess fluids and loose bodies that may be in the knee joint. Debridement, in comparison, may include the introduction of saline into the joint, in addition to the smoothening of bone surface without any further intervention (less invasive forms of debridement), or the addition of more invasive procedures such as abrasion, partial or full meniscectomy, synovectomy, or osteotomy (referred to as debridement in combination with meniscectomy or other procedures). The focus of this health technology assessment is on the effectiveness of lavage, and debridement (with or without meniscal tear resection). THE MEDICAL ADVISORY SECRETARIAT FOLLOWED ITS STANDARD PROCEDURES AND SEARCHED THESE ELECTRONIC DATABASES: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and The International Network of Agencies for Health Technology Assessment. THE KEYWORDS SEARCHED WERE: arthroscopy, debridement, lavage, wound irrigation, or curettage; arthritis, rheumatoid, osteoarthritis; osteoarthritis, knee; knee or knee joint. TIME FRAME: Only 2 previous health technology assessments were identified, one of which was an update of the other, and included 3 of 4 randomized controlled trials (RCTs) from the first report. Therefore, the search period for inclusion of studies in this assessment was January 1, 1995 to April 24, 2005. EXCLUDED WERE: case reports, comments, editorials, and letters. Identified were 335 references, including previously published health technology assessments, and 5 articles located through a manual search of references from published articles and health technology assessments. These were examined against the criteria, as described below, which resulted in the inclusion of 1 health technology assessment and its corresponding update, and 4 articles (2 RCTs and 2 level 4 studies) for arthroscopic lavage and 8 papers (2 RCTs and 6 level 4 studies) for arthroscopic debridement. English-language articles from PubMed, EMBASE, Cochrane Systematic Reviews, and health technology assessments from January 1, 1995 onwardStudies on OA of the knee with a focus on the outcomes of motor function and painStudies of arthroscopic procedures onlyStudies in which meniscal tear resection/meniscectomy (partial or full) has been conducted in conjunction with lavage or debridement. Studies that focus on inflammatory OA, joint tuberculosis, septic joints, psoriatic joints (e.g., psoriatic knee joint synovitis), synovitis, chondropathy of the knee and gonarthrosis (which includes varotic gonarthrosis)Studies that focus on rheumatoid arthritisStudies that focus on meniscal tears from an acute injury (e.g., sports injury)Studies that are based on lavage or debridement for microfracture of the kneeStudies in which other surgical procedures (e.g., high tibial osteotomy, synovectomy, have been conducted in addition to lavage/debridement)Studies based on malalignment of the knee (e.g., varus/valgus arthritic conditions).Studies that compare lavage to lavage plus drug therapyStudies on procedures that are not arthroscopic (i.e., visually guided) (e.g., nonarthroscopic lavage)Studies of OA in children. Arthroscopic lavage or debridement, with or without meniscectomy, for the treatment of motor function symptoms and pain associated with OA of the knee. Studies in which there was a comparison group of either diseased or healthy subjects or one in which subjects were their own control were included. Comparisons to other treatments included placebo (or sham) arthroscopy. Sham arthroscopy involved making small incisions and manipulating the knee, without the insertion of instruments. IN EARLY OA OF THE KNEE WITH PAIN REFRACTORY TO MEDICAL TREATMENT, THERE IS LEVEL 1B EVIDENCE THAT: Arthroscopic lavage gives rise to a statistically significant, but not clinically meaningful effect in improving pain (WOMAC pain and VAS pain) up to 12 months following surgery. The effect on joint function (WOMAC function) and the primary outcome (WOMAC aggregate) was neither statistically nor clinically significant. IN MODERATE OR SEVERE OA OF THE KNEE WITH PAIN REFRACTORY TO MEDICAL TREATMENT, THERE IS: Level 1b evidence that the effect on pain and function of arthroscopic lavage (10 L saline) and debridement (with 10 L saline lavage) is not statistically significant up to 24 months following surgery.Level 2 evidence that arthroscopic debridement (with 3 L saline lavage) is effective in the control of pain in severe OA of the medial femoral condyle for up to 5 years.For debridement in combination with meniscectomy, there is level 4 evidence that the procedure, as appropriate, might be effective in earlier stages, unicompartmental disease, shorter symptom duration, sudden onset of mechanical symptoms, and preoperative full range of motion. However, as these findings are derived from very poor quality evidence, the identification of subsets of patients that may benefit from this procedure requires further testing.In patients with pain due to a meniscal tear, of the medial compartment in particular, repair of the meniscus results in better pain control at 2 years following surgery than if the pain is attributable to other causes. There is insufficient evidence to comment on the effectiveness of lateral meniscus repair on pain control. Arthroscopic debridement of the knee has thus far only been found to be effective for medial compartmental OA. All other indications should be reviewed with a view to reducing arthroscopic debridement as an effective therapy. Arthroscopic lavage of the knee is not indicated for any stage of OA. There is very poor quality evidence on the effectiveness of debridement with partial meniscectomy in the case of meniscal tears in OA of the knee.


Electrochemical determination of thioredoxin redox states.
Thioredoxin (TRX) is a general protein disulfide reductase with a large number of biological functions, including its roles in human diseases. The TRX redox mechanism is based on reversible oxidation of two cysteine thiol groups to a disulfide, accompanied by the transfer of two protons. Using constant-current chronopotentiometric stripping analysis (CPSA) and the electrocatalytic TRX peak H, we have determined redox states of TRX at submicromolar TRX concentrations. A concentration of 1 nM TRX produces a well-developed peak H at moderate accumulation time without stirring. On the basis of this peak, interactions of 4-hydroxy-2-nonenal (HNE, product of lipid peroxidation) with TRX and the formation of TRX-HNE adducts were studied. CPSA of TRX at a carbon electrode is less sensitive and does not discriminate between reduced and oxidized forms of TRX.


The archaeal RNA polymerase subunit P and the eukaryotic polymerase subunit Rpb12 are interchangeable in vivo and in vitro.
The general subunit of all three eukaryotic RNA polymerases, Rpb12, and subunit P of the archaeal enzyme show sequence similarities in their N-terminal zinc ribbon and some highly conserved residues in the C-terminus. We report here that archaeal subunit P under the control of a strong yeast promoter could complement the lethal phenotype of a RPB12 deletion mutant and that subunit Rpb12 from yeast can functionally replace subunit P during reconstitution of the archaeal RNA polymerase. The DeltaP enzyme is unable to form stable open complexes, but can efficiently extend a dinucleotide on a premelted template or RNA on an elongation scaffold. This suggests that subunit P is directly or indirectly involved in promoter opening. The activity of the DeltaP enzyme can be rescued by the addition of Rpb12 or subunit P to transcription reactions. Mutation of cysteine residues in the zinc ribbon impair the activity of the enzyme in several assays and this mutated form of P is rapidly replaced by wild-type P in transcription reactions. The conserved zinc ribbon in the N-terminus seems to be important for proper interaction of the complete subunit with other RNA polymerase subunits and a 17-amino-acid C-terminal peptide is sufficient to support all basic RNA polymerase functions in vitro.


Role of DNA binding sites and slow unbinding kinetics in titration-based oscillators.
Genetic oscillators, such as circadian clocks, are constantly perturbed by molecular noise arising from the small number of molecules involved in gene regulation. One of the strongest sources of stochasticity is the binary noise that arises from the binding of a regulatory protein to a promoter in the chromosomal DNA. In this study, we focus on two minimal oscillators based on activator titration and repressor titration to understand the key parameters that are important for oscillations and for overcoming binary noise. We show that the rate of unbinding from the DNA, despite traditionally being considered a fast parameter, needs to be slow to broaden the space of oscillatory solutions. The addition of multiple, independent DNA binding sites further expands the oscillatory parameter space for the repressor-titration oscillator and lengthens the period of both oscillators. This effect is a combination of increased effective delay of the unbinding kinetics due to multiple binding sites and increased promoter ultrasensitivity that is specific for repression. We then use stochastic simulation to show that multiple binding sites increase the coherence of oscillations by mitigating the binary noise. Slow values of DNA unbinding rate are also effective in alleviating molecular noise due to the increased distance from the bifurcation point. Our work demonstrates how the number of DNA binding sites and slow unbinding kinetics, which are often omitted in biophysical models of gene circuits, can have a significant impact on the temporal and stochastic dynamics of genetic oscillators.


Arbitrarily accurate dynamical control in open quantum systems.
We show that open-loop dynamical control techniques may be used to synthesize unitary transformations in open quantum systems in such a way that decoherence is perturbatively compensated for to a desired (in principle arbitrarily high) level of accuracy, which depends only on the strength of the relevant errors and the achievable rate of control modulation. Our constructive and fully analytical solution employs concatenated dynamically corrected gates, and is applicable independently of detailed knowledge of the system-environment interactions and environment dynamics. Explicit implications for boosting quantum gate fidelities in realistic scenarios are addressed.


Damage limited to the hippocampal region produces long-lasting memory impairment in monkeys.
Research in humans and monkeys has demonstrated a system of anatomically related structures in the medial temporal lobe that is important for memory function. This system is comprised of the hippocampal region (i.e., the dentate gyrus, hippocampus proper and subicular complex) and the entorhinal, perirhinal, and parahippocampal cortices. While the hippocampal region has long been thought to be important in memory, there are few systematic studies in primates of the effects on memory of damage limited to the hippocampal region. We have used magnetic resonance imaging techniques, together with a stereotaxic approach, to produce bilateral lesions limited to the hippocampal region (the H lesion). Damage to the adjacent perirhinal, entorhinal, and parahippocampal cortex was minimal. Monkeys with the H lesion exhibited significant and long-lasting impairment on the delayed non-matching to sample task. At the same time, on this and other amnesia-sensitive tasks, monkeys with the H lesion performed better overall than monkeys with lesions of the hippocampal region that also included damage to the adjacent entorhinal and parahippocampal cortices (the H+ lesion). These findings show that, first, the hippocampal region itself is essential for normal memory function; and second, the adjacent entorhinal and parahippocampal cortices, either alone or in combination, are also an essential component of the medial temporal lobe memory system.


An in-depth human health risk assessment of potentially toxic elements in highly polluted riverine soils, Příbram (Czech Republic).
Environmental pollution by potentially toxic element (PTE) and the associated health risks in humans are increasingly becoming a global challenge. The current study is an in-depth assessment of PTEs including the often studied lead (Pb), manganese (Mn), zinc (Zn), arsenic (As) and the less-studied titanium (Ti), rubidium (Rb), strontium (Sr), zirconium (Zr), barium (Ba) and thorium (Th) in highly polluted floodplain topsoil samples from the Litavka River, Czech Republic. Soil chemical properties including carbon (Cox) and reaction (pH_H2O) together with iron (Fe) were assessed in the same soils. A portable X-ray fluorescence spectrometer (p-XRFS) (Delta Premium) was used to measure the PTEs and Fe contents of the soils. Soil organic carbon and reaction pH were determined following routine laboratory procedures. The concentration level of each PTE was compared against world average and crustal values, with the majority of elements exceeding the aforementioned geochemical background levels. Distributions of the PTEs were mapped. Two pollution assessment indices including enrichment factor (EF) and pollution index (PI) levels were calculated and their means for Zn (43.36, 55.54), As (33.23, 43.59) and Pb (81.08, 103.21) show that these elements were enriched. Zn, As and Pb accounted for the high pollution load index (PLI) levels observed in the study. The EF and PI distribution maps corresponded with the concentration distribution maps for each PTE. On health risk assessment, hazard quotients (HQ) in different human groups varied. Children had the highest HQs for all PTEs than adults (women and men). PTEs with high HQ levels in distinct human groups were As, Zr and Pb. Zirconium is a less likely element to pose a health risk in humans. Nonetheless, it should be kept in check despite its low pollution occurrence.


Body mass index and the risk of cancers of the gastric cardia and distal stomach in Shanghai, China.
The divergent incidence patterns of gastric cardia and distal stomach cancers suggest different etiologies. Although obesity has recently been linked to cardia cancer in Western populations, its association with distal stomach cancer remains unclear. This study examined the relation of anthropometric measurements to risk by subsites of stomach cancer in a Chinese population. We identified 1124 population-based cases of stomach cancer, ages 20-69 years, newly diagnosed between December 1988 and November 1989 in Shanghai, China. Controls (n = 1451) were randomly selected from permanent Shanghai residents and frequency-matched to cases by age and sex. Information on demographic characteristics, height and weight, diet, smoking, and other exposures was obtained by trained interviewers in person. The body mass index (BMI) was calculated as weight in kilograms divided by height in square meters and categorized into quartiles based on the distribution among controls. Odds ratios and 95% confidence intervals were estimated using logistic regression models, simultaneously adjusting for age, education, income, cigarette smoking (men only), alcohol drinking (men only), intake of total calories, and chronic gastric diseases. For gastric cardia cancer, the odds ratios among men were 1.4, 1.5, and 3.0 in the second, third, and fourth quartiles of usual BMI (P for trend, < 0.01). Among women, elevated risks also were associated with excess weight, but the gradient in risk was not smooth. Risk patterns for usual body weight, maximum BMI, and minimum BMI were similar to those found for usual BMI. For distal stomach cancer, no association with usual BMI was observed among men, but a slightly elevated risk was seen among women. Our observations in China support recent findings in Western populations that obesity contributes to the risk of gastric cardia cancer, especially among men.


Ultrasound-guided chest biopsies.
Pulmonary nodules that are surrounded by aerated lung cannot be visualized with sonography. Therefore, percutaneous biopsy must be guided with computed tomography or fluoroscopy. Although this restriction only applies to central lung nodules, it has permeated referral patterns for other thoracic lesions and has retarded the growth of ultrasound-guided interventions. Nevertheless, sonography is an extremely flexible modality that can expeditiously guide many biopsy procedures in the thorax. Peripheral pulmonary nodules can be successfully biopsied with success rates exceeding 90% and complications rates of less than 5%. Orienting the probe parallel to the intercostal space facilitates biopsies of peripheral pulmonary nodules. Anterior mediastinal masses that extend to the parasternal region are often easily approachable provided the internal mammary vessels, costal cartilage, and deep great vessels are identified and avoided. Superior mediastinal masses can be sampled from a suprasternal or supraclavicular approach. Phased array probes or tightly curved arrays may provide improved access for biopsies in this location. Posterior mediastinal masses are more difficult to biopsy with ultrasound guidance because of the overlying paraspinal muscles. However, when posterior mediastinal masses extend into the posterior medial pleural region, they can be biopsied with ultrasound guidance. Because many lung cancers metastasize to the supraclavicular nodes, it is important to evaluate the supraclavicular region when determining the best approach to obtain a tissue diagnosis. When abnormal supraclavicular nodes are present, they often are the easiest and safest lesions to biopsy.


Phosphorylation of signal transducer and activator of transcription-3 (Stat3) after focal cerebral ischemia in rats.
JAK-STAT is the major downstream signal pathway of interleukin-6 (IL-6) cytokine family and is regulated by Tyr705 phosphorylation of Stat3. The present study examined the extent and the localization of phosphorylated Stat3 protein in brain tissue after focal ischemia in rats. The localizations of unphosphorylated and phosphorylated Stat3 were immunohistochemically examined in rats after 0.5 to 168 h of reperfusion following 1.5 h of middle cerebral artery occlusion (MCAO), induced by the intraluminal suture method. Absolute phosphorylated Stat3 immunoreactive cell counts were made in the cerebral cortex (ischemic core, peri-ischemia region, and contralareral cortex) and lateral striatal regions on both the ischemic and the contralateral sides. Stat3 protein was localized diffusely in cortical and striatal neurons in the sham-operated animals. Although weak Stat3 staining was detected in damaged neurons in the ischemic region, activated microglia, astrocytes, and endothelial cells clearly expressed Stat3 in this region. On the other hand, the sham group showed no phosphorylated Stat3 immunoreactivity. Phosphorylated Stat3 immunoreactivity was first detected in neurons after 3.5 h of reperfusion in each cortical and striatal region. Thereafter, Stat3 phosphorylation was marked in neurons in the peri-infarct region, peaked at 24 h, and then gradually declined throughout the reperfusion period. Endothelial cells expressed phosphorylated Stat3 in the ischemic core at 48 h of reperfusion. To identify the cellular source of phosphorylated Stat3, lectin histochemical study and immunohistochemical study with anti-microtubule-associated proten-2 and anti-glial fibrillary acidic protein antibodies were carried out. Double-staining immunohistochemistry with these cellular makers revealed phosphorylated Stat3 to be present in neurons, but in neither astrocytes nor microglia/macrophages. These results were also confirmed be western blot analysis. The present results indicate that Stat3 activation occurs in neurons and endothelial cells only during post-ischemic reperfusion despite widespread expression of IL-6 cytokines.


BET Bromodomain Inhibitors Which Permit Treg Function Enable a Combinatorial Strategy to Suppress GVHD in Pre-clinical Allogeneic HSCT.
A recent approach for limiting production of pro-inflammatory cytokines has been to target bromodomain and extra-terminal (BET) proteins. These epigenetic readers of histone acetylation regulate transcription of genes involved in inflammation, cardiovascular disease, and cancer. Development of BET inhibitors (BETi) has generated enormous interest for their therapeutic potential. Because inflammatory signals and donor T cells promote graft-versus-host disease (GVHD), regulating both pathways could be effective to abrogate this disorder. The objective of the present study was to identify a BETi which did not interfere in vivo with CD4+FoxP3+ regulatory T cell (Treg) expansion and function to utilize together with Tregs following allogeneic hematopoietic stem cell transplantation (aHSCT) to ameliorate GVHD. We have reported that Tregs can be markedly expanded and selectively activated with increased functional capacity by targeting TNFRSF25 and CD25 with TL1A-Ig and low dose IL-2, respectively. Here, mice were treated over 7 days (TL1A-Ig + IL-2) together with BETi. We found that the BETi EP11313 did not decrease frequency/numbers or phenotype of expanded Tregs as well as effector molecules, such as IL-10 and TGF-β. However, BETi JQ1 interfered with Treg expansion and altered subset distribution and phenotype. Notably, in Treg expanded mice, EP11313 diminished tnfa and ifng but not il-2 RNA levels. Remarkably, Treg pSTAT5 expression was not affected by EP11313 supporting the notion that Treg IL-2 signaling remained intact. MHC-mismatched aHSCT (B6 → BALB/c) was performed using in vivo expanded donor Tregs with or without EP11313 short-term treatment in the recipient. Early post-transplant, improvement in the splenic and LN CD4/CD8 ratio along with fewer effector cells and high Treg levels in aHSCT recipients treated with expanded Tregs + EP11313 was detected. Interestingly, this group exhibited a significant diminution of GVHD clinical score with less skin and ocular involvement. Finally, using low numbers of highly purified expanded Tregs, improved clinical GVHD scores were observed in EP11313 treated recipients. In total, we conclude that use of this novel combinatorial strategy can suppress pre-clinical GVHD and posit, in vivo EP11313 treatment might be useful combined with Treg expansion therapy for treatment of diseases involving inflammatory responses.


Testosterone replacement therapy in men with prostate cancer: a time-varying analysis.
The use of testosterone replacement therapy (TRT) in men with prostate cancer is controversial given concerns of androgen-related cancer progression. Although emerging evidence suggests that TRT may be safe in this setting, no study has investigated dose-related effects. We used time-varying analysis to determine whether increasing TRT exposure is associated with worse outcomes. Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1991 to 2007. Subjects treated with TRT were stratified by duration of treatment. Weighted propensity score methods were used to adjust for differences between groups. A Cox proportional hazards model was constructed to assess the effect of injectable TRT exposure on outcomes. Overall mortality (OM), prostate cancer-specific mortality (PCSM), and use of salvage androgen deprivation therapy (ADT). Men treated with TRT, regardless of duration, did not experience higher OM or PCSM (all hazard ratio [HR] <1.0, all P ≤ 0.002). We found no difference in use of salvage ADT in the ≤ 30-day and 31-60 day groups compared with no-TRT (HR 1.23 and 1.05, P=0.06 and 0.81, respectively), whereas it was lower for men on long-term TRT (HR 0.70, P=0.04). TRT following prostate cancer diagnosis and treatment does not increase mortality or the use of salvage ADT. Using time-varying analysis, we demonstrate that longer duration of TRT is not associated with adverse mortality or greater need for ADT.


Genome replication, virion secretion, and e antigen expression of naturally occurring hepatitis B virus core promoter mutants.
The core promoter mutants of hepatitis B virus (HBV) emerge as the dominant viral population at the late HBeAg and the anti-HBe stages of HBV infection, with the A1762T/G1764A substitutions as the hotspot mutations. The double core promoter mutations were found by many investigators to moderately enhance viral genome replication and reduce hepatitis B e antigen (HBeAg) expression. A much higher replication capacity was reported for a naturally occurring core promoter mutant implicated in the outbreak of fulminant hepatitis, which was caused by the neighboring C1766T/T1768A mutations instead. To systemically study the biological properties of naturally occurring core promoter mutants, we amplified full-length HBV genomes by PCR from sera of HBeAg(+) individuals infected with genotype A. All 12 HBV genomes derived from highly viremic sera (5 x 10(9) to 5.7 x 10(9) copies of viral genome/ml) harbored wild-type core promoter sequence, whereas 37 of 43 clones from low-viremia samples (0.2 x 10(7) to 4.6 x 10(7) copies/ml) were core promoter mutants. Of the 11 wild-type genomes and 14 core promoter mutants analyzed by transfection experiments in human hepatoma cell lines, 6 core promoter mutants but none of the wild-type genomes replicated at high levels. All had 1762/1764 mutations and an additional substitution at position 1753 (T to C), at position 1766 (C to T), or both. Moreover, these HBV clones varied greatly in their ability to secrete enveloped viral particles irrespective of the presence of core promoter mutations. High-replication clones with 1762/1764/1766 or 1753/1762/1764/1766 mutations expressed very low levels of HBeAg, whereas high-replication clones with 1753/1762/1764 triple mutations expressed high levels of HBeAg. Experiments with site-directed mutants revealed that both 1762/1764/1766 and 1753/1762/1764/1766 mutations conferred significantly higher viral replication and lower HBeAg expression than 1762/1764 mutations alone, whereas the 1753/1762/1764 triple mutant displayed only mild reduction in HBeAg expression similar to the 1762/1764 mutant. Thus, core promoter mutations other than those at positions 1762 and 1764 can have major impact on viral DNA replication and HBeAg expression.


Temperature-dependent Photodegradation in UV-resonance Raman Spectroscopy.
Temperature-dependent photodegradation during UV-resonance Raman spectroscopy was investigated. Photodegradation was quantitatively probed by monitoring the temporal evolution of UV-resonance Raman spectra obtained from bacteriochlorophyll (BChl) showing, resonance effect at a 355-nm excitation wavelength. At 80 K, the molecular photodecomposition rate was 5-times lower than that at room temperature. The decomposition rates of BChl were analyzed by the Arrhenius formula, indicating that the mechanism of photodegradation includes a thermal process having an activation energy of 1.4 kJ/mol.


Completeness of carotid intima media thickness measurements depends on body composition: the RADIANCE 1 and 2 trials.
Ultrasound protocols to measure carotid intima media thickness (CIMT) differ considerably with regard to the inclusion of the number of carotid segments and angles used. Detailed information on the completeness of CIMT information is often lacking in published reports, and at most, overall percentages are presented. We therefore decided to study the completeness of CIMT measurements and its relation with vascular risk factors using data from two CIMT intervention studies: one among familial hypercholesterolemia (FH) patients, the Rating Atherosclerotic Disease change by Imaging With A New CETP Inhibitor (RADIANCE 1), and one among mixed dyslipidemia (MD) patients, the Rating Atherosclerotic Disease change by Imaging With A New CETP Inhibitor (RADIANCE 2). We used baseline ultrasound scans from the RADIANCE 1 (n=872) and RADIANCE 2 (n=752) studies. CIMT images were recorded for 12 artery-wall combinations (near and far walls of the left and right common carotid artery (CCA), bifurcation (BIF) and internal carotid artery (ICA) segments) at 4 set angles, resulting in 48 possible measurements per patient. The presence or absence of CIMT measurements was assessed per artery-wall combination and per angle. The relation between completeness and patient characteristics was evaluated with logistic regression analysis. In 89% of the FH patients, information on CIMT could be obtained on all twelve carotid segments, and in 7.6%, eleven segments had CIMT information (nearly complete 96.6%). For MD patients this was 74.6% and 17.9%, respectively (nearly complete: 92.5%). Increased body mass index and increased waist circumference were significantly (p=0.01) related to less complete data in FH patients. For MD patients, relations were seen with increased waist circumference (p<0.01). Segment-specific data indicated that in FH patients, completeness was less for the near wall of the left (96%) and right internal carotid artery (94%) as compared to other segments (all >98%). In MD patients, completeness was lower for the near wall of both the right and left carotid arteries: 86.0% and 90.8%, respectively, as compared to other segments (all >97%). With the current ultrasound protocols it is possible to obtain a very high level of completeness. Apart from the population studied, body mass index and waist circumference are important in achieving complete CIMT measurements.


Evidence-based interventional pain medicine according to clinical diagnoses. 16. Complex regional pain syndrome.
Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy is a pain syndrome with an unclear pathophysiology and unpredictable clinical course. The disease is often therapy resistant, the natural course not always favorable. The diagnosis of CRPS is based on signs and symptoms derived from medical history and physical examination. Pharmacological pain management and physical rehabilitation of limb function are the main pillars of therapy and should be started as early as possible. If, however, there is no improvement of limb function and persistent severe pain, interventional pain management techniques may be considered. Intravenous regional blocks with guanethidine did not prove superior to placebo but frequent side effects occurred.Therefore this technique receives a negative recommendation (2 A-). Sympathetic block is the interventional treatment of first choice and has a 2 B+ rating. Ganglion stellatum (stellate ganglion) block with repeated local anesthetic injections or by radiofrequency denervation after positive diagnostic block is documented in prospective and retrospective trials in patients suffering from upper limb CRPS. Lumbar sympathetic blocks can be performed with repeated local anesthetic injections. For a more prolonged lumbar sympathetic block radiofrequency treatment is preferred over phenol neurolysis because effects are comparable whereas the risk for side effects is lower (2 B+). For patients suffering from CRPS refractory to conventional treatment and sympathetic blocks, plexus brachialis block or continuous epidural infusion analgesia coupled with exercise therapy may be tried (2 C+). Spinal cord stimulation is recommended if other treatments fail to improve pain and dysfunction (2 B+). Alternatively peripheral nerve stimulation can be considered, preferentially in study conditions (2 C+).


Cortisol is responsible for positive and negative effects in the ovarian maturation induced by the exposure to acute stressors in Nile tilapia, Oreochromis niloticus.
The aim of the present study was to evaluate the effect of acute stress and cortisol injection on oocyte final maturation process in female Nile tilapia (Oreochromis niloticus). Handling followed by a prophylactic treatment (0.3 mL L(-1) H(2)O(2), 5 g L(-1) NaCl solution during 30 min) and an environmental change (transfer from a 2 m(3) fibreglass square tank to 50 L aquaria) were used as acute stressors and compared to a single cortisol injection (0.5 or 5 mg kg(-1) body weight). For both acute stress and cortisol injection (0.5 mg kg(-1) body weight), serum cortisol level was significantly increased from 2.3 to 134.1 ng mL(-1) 1 h post-stress/injection and returned to a resting basal value 24 h after the stress/injection. In fish injected with 5 mg kg(-1) body weight cortisol, mean serum cortisol level reached a peak up to 2500 ng mL(-1) 1 h after injection. 63 % of the females (mean body weight: 242 ± 4 g) submitted to the acute stress ovulated within 72 h after the stress. In the same way, cortisol injection (5 mg kg(-1) body weight) at the 10th day of the maturation cycle led to a twofold reduction of the time before ovulation compared to vehicle injected control fish. Relative and total fecundity were significantly decreased in females submitted to an acute stress or cortisol injected at 5 mg kg(-1) body weight, but not fertilization or hatching rates. In conclusion, acute stress and cortisol induction exert both positive and negative effects on the final reproductive process in O. niloticus, and cortisol is the endocrine mediator causing these changes.


Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.
Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable.


Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis.
Wnt/beta-catenin signaling plays key roles in tooth development, but how this pathway intersects with the complex interplay of signaling factors regulating dental morphogenesis has been unclear. We demonstrate that Wnt/beta-catenin signaling is active at multiple stages of tooth development. Mutation of beta-catenin to a constitutively active form in oral epithelium causes formation of large, misshapen tooth buds and ectopic teeth, and expanded expression of signaling molecules important for tooth development. Conversely, expression of key morphogenetic regulators including Bmp4, Msx1, and Msx2 is downregulated in embryos expressing the secreted Wnt inhibitor Dkk1 which blocks signaling in epithelial and underlying mesenchymal cells. Similar phenotypes are observed in embryos lacking epithelial beta-catenin, demonstrating a requirement for Wnt signaling within the epithelium. Inducible Dkk1 expression after the bud stage causes formation of blunted molar cusps, downregulation of the enamel knot marker p21, and loss of restricted ectodin expression, revealing requirements for Wnt activity in maintaining secondary enamel knots. These data place Wnt/beta-catenin signaling upstream of key morphogenetic signaling pathways at multiple stages of tooth development and indicate that tight regulation of this pathway is essential both for patterning tooth development in the dental lamina, and for controlling the shape of individual teeth.


Impact of ABCB1 single nucleotide polymorphisms 1236C>T and 2677G>T on overall survival in FLT3 wild-type de novo AML patients with normal karyotype.
Drug resistance is a clinically relevant problem in the treatment of acute myeloid leukaemia (AML). We have previously reported a relationship between single nucleotide polymorphisms (SNPs) of ABCB1, encoding the multi-drug transporter P-glycoprotein, and overall survival (OS) in normal karyotype (NK)-AML. Here we extended this material, enabling subgroup analysis based on FLT3 and NPM1 status, to further elucidate the influence of ABCB1 SNPs. De novo NK-AML patients (n = 201) were analysed for 1199G>A, 1236C>T, 2677G>T/A and 3435C>T, and correlations to outcome were investigated. FLT3 wild-type 1236C/C patients have significantly shorter OS compared to patients carrying the variant allele; medians 20 vs. 49 months, respectively, P = 0·017. There was also an inferior outcome in FLT3 wild-type 2677G/G patients compared to patients carrying the variant allele, median OS 20 vs. 35 months, respectively, P = 0·039. This was confirmed in Cox regression analysis. Our results indicate that ABCB1 1236C>T and 2677G>T may be used as prognostic markers to distinguish relatively high risk patients in the intermediate risk FLT3 wild-type group, which may contribute to future individualizing of treatment strategies.


Total hip and total knee arthroplasties: trends and disparities revisited.
Total joint arthroplasties are recognized as being effective in the treatment of joint disease and making a significant difference in patients' quality of life. Understanding the trends and disparities in use of these procedures is important for policy decisions. However, research on these issues has been limited because of the suboptimal samples used. To study trends and racial and economic disparities associated with total hip and total knee arthroplasties, we used a large national database, Nationwide Inpatient Sample, 1996-2005, which may be best suited for elucidating trends and disparities in treatment use. Primary and revision hip and knee arthroplasties were the primary outcomes. Rates of use were computed by count per 100,000 persons in the population. Logistic regression was used to examine the associations between disparity factors and each outcome, where regressors included age, sex, race, regional income, hospital characteristics, payer, comorbidities, and obesity. Between 1996 and 2005, primary arthroplasty rates have increased, but revision rates only minimally. Racial disparities were larger than income disparities. Our study also revealed that racial disparities were not confined to the elderly or to low-income populations. This may mean that there is an unmet need for these medical procedures among racial minorities.


Non-genomic effects of the Pregnane X Receptor negatively regulate platelet functions, thrombosis and haemostasis.
The pregnane X receptor (PXR) is a nuclear receptor (NR), involved in the detoxification of xenobiotic compounds. Recently, its presence was reported in the human vasculature and its ligands were proposed to exhibit anti-atherosclerotic effects. Since platelets contribute towards the development of atherosclerosis and possess numerous NRs, we investigated the expression of PXR in platelets along with the ability of its ligands to modulate platelet activation. The expression of PXR in human platelets was confirmed using immunoprecipitation analysis. Treatment with PXR ligands was found to inhibit platelet functions stimulated by a range of agonists, with platelet aggregation, granule secretion, adhesion and spreading on fibrinogen all attenuated along with a reduction in thrombus formation (both in vitro and in vivo). The effects of PXR ligands were observed in a species-specific manner, and the human-specific ligand, SR12813, was observed to attenuate thrombus formation in vivo in humanised PXR transgenic mice. PXR ligand-mediated inhibition of platelet function was found to be associated with the inhibition of Src-family kinases (SFKs). This study identifies acute, non-genomic regulatory effects of PXR ligands on platelet function and thrombus formation. In combination with the emerging anti-atherosclerotic properties of PXR ligands, these anti-thrombotic effects may provide additional cardio-protective benefits.


Proton structure from the measurement of 2S-2P transition frequencies of muonic hydrogen.
Accurate knowledge of the charge and Zemach radii of the proton is essential, not only for understanding its structure but also as input for tests of bound-state quantum electrodynamics and its predictions for the energy levels of hydrogen. These radii may be extracted from the laser spectroscopy of muonic hydrogen (μp, that is, a proton orbited by a muon). We measured the 2S(1/2)(F=0)-2P(3/2)(F=1) transition frequency in μp to be 54611.16(1.05) gigahertz (numbers in parentheses indicate one standard deviation of uncertainty) and reevaluated the 2S(1/2)(F=1)-2P(3/2)(F=2) transition frequency, yielding 49881.35(65) gigahertz. From the measurements, we determined the Zemach radius, r(Z) = 1.082(37) femtometers, and the magnetic radius, r(M) = 0.87(6) femtometer, of the proton. We also extracted the charge radius, r(E) = 0.84087(39) femtometer, with an order of magnitude more precision than the 2010-CODATA value and at 7σ variance with respect to it, thus reinforcing the proton radius puzzle.


Selective outgrowth of fimbriate bacteria in static liquid medium.
Competitive mixed cultures were grown from inocula of a large number of bacteria of a genotypically nonfimbriate (fim(-)) strain of Salmonella typhimurium and a small number of a genotypically fimbriate (fim(+)) variant strain that formed type 1 fimbriae and had been derived from the fim(-) strain by phage transduction. The fim(+) strain differed from the fim(-) strain in fermenting l-rhamnose (rha(+)), and the viable fim(+) and fim(-) bacteria present in the cultures after different periods at 37 C were counted differentially in platings on rhamnose media. When the cultures were grown under aerobic static conditions in tubes of nutrient broth, the fim(+) bacteria rapidly outgrew the fim(-) bacteria, so that, although starting as a small minority (e.g., 1 in 10(7)), they approached or surpassed the number of the fim(-) in 48 hr. A pellicle consisting of fimbriate bacteria was formed on the surface of the broth between 6 and 24 hr, and it is thought that the advantage of access to atmospheric oxygen enjoyed by these bacteria in the pellicle enabled them to outgrow the fim(-) bacteria confined in the oxygen-depleted broth. The fim(+) bacteria did not show selective outgrowth in mixed cultures grown in broth aerated by continuous shaking, in static broth incubated anaerobically in hydrogen, and on aerobic agar plates, i.e., under conditions not allowing an advantage from pellicle formation. The outgrowth of fim(+) bacteria in aerobic static broth was prevented by the addition of alpha-methylmannoside, a substance that inhibits the adhesive and early pellicle-forming properties of bacteria with type 1 fimbriae. A motile flagellate (fla(+)) variant of a fim(-)fla(-) strain of S. typhimurium outgrew its parent strain in mixed cultures in aerobic static broth, but the selective advantage conferred by motility was weaker than that conferred by fimbriation.


The effect of aromatherapy by essential oil of orange on anxiety during labor: A randomized clinical trial.
Labor is a stressful situation that may have an adverse impact. Aromatherapy is a method to control anxiety and stress of women. This study was conducted to investigate the effect of aromatherapy using essential oil of orange on women's anxiety during labor. In this clinical trial study, 100 women during labor were randomly assigned to two groups: intervention group and control group. The women in the intervention group were exposed to orange essential oil, but the women in the control group were exposed to distilled water. The women's anxiety was assessed using the Spielberger inventory. Moreover, physiological parameters such as systolic and diastolic blood pressure, respiration and pulse rates were assessed in all the women before and 20 min after the intervention. The data were analyzed by Chi-square, Wilcoxon, paired t-test, and Mann-Whitney U test. Data were evaluated with the SPSS 16 program. The significance level of P < 0.05 was considered. The level of anxiety of women in both intervention (P = 0.03) and control (P = 0.003) groups reduced after the intervention. However, the reduction was more in the intervention group (difference in anxiety scores after the intervention in comparison to before intervention = -3.08) in comparison to the control group (score = -1.14). No significant change was found in the physiological parameters of women in the intervention group after the intervention. Aromatherapy is a noninvasive and effective method to help women overcome their anxiety during labor. Orange scent can be useful in childbirth units to help women who are experiencing stress in labor.


Tension Among Women in North India: An Idiom of Distress and a Cultural Syndrome.
The existing literature on Indian ethnopsychology has long asserted that somatization is a key aspect of experiences of distress. The study of idioms of distress arose out of work done in India (Nichter in Cult Med Psychiatry 5(4):379-408, 1981), but ironically, little subsequent work has systematically explored idioms of distress in this part of the world. This ethnographic study focused on the term tension (tenśan) and its relation to a cultural syndrome among women in urban North India. This syndrome appears to involve rapid-onset anger, irritation, rumination, and sleeplessness as key symptoms. It is often linked to specific circumstances such as domestic conflict and is associated with the stresses of modern urban life. People who report more symptoms of tension had consistently higher scores on the Hopkins Symptoms Checklist-25 for depression and anxiety. In this cultural context where psychiatric care is highly stigmatized, the language of tension can aid providers of mental healthcare (many of whom, in India, are not psychiatrists or psychologists) to identify and communicate effectively with potential patients whose mental healthcare needs might otherwise go unaddressed.


OXIDATION OF CARBON-14-LABELED ENDOGENOUS LIPIDS BY ISOLATED PERFUSED RAT HEART.
Lipids of the rat heart were labeled with carbon-14 in vivo. The production of C(14)O(2) during the subsequent perfusion of these glycogen-depleted hearts with buffer, but without added substrate, provided direct evidence of the oxidation of endogenous heart lipids. The net decrease in phospholipid content alone could account for 75 percent of the total metabolic CO(2) formed.


Natural resource management at four social scales: psychological type matters.
Understanding organisation at different social scales is crucial to learning how social processes play a role in sustainable natural resource management. Research has neglected the potential role that individual personality plays in decision making in natural resource management. In the past two decades natural resource management across rural Australia has increasingly come under the direct influence of voluntary participatory groups, such as Catchment Management Authorities. The greater complexity of relationships among all stakeholders is a serious management challenge when attempting to align their differing aspirations and values at four social institutional scales-local, regional, state and national. This is an exploratory study on the psychological composition of groups of stakeholders at the four social scales in natural resource management in Australia. This article uses the theory of temperaments and the Myers-Briggs Type Indicator (MBTI) to investigate the distribution of personality types. The distribution of personality types in decision-making roles in natural resource management was markedly different from the Australian Archive sample. Trends in personality were found across social scales with Stabilizer temperament more common at the local scale and Theorist temperament more common at the national scale. Greater similarity was found at the state and national scales. Two temperaments comprised between 76 and 90% of participants at the local and regional scales, the common temperament type was Stabilizer. The dissimilarity was Improviser (40%) at the local scale and Theorist (29%) at the regional scale. Implications for increasing participation and bridging the gap between community and government are discussed.


Reasons People Who Use Opioids Do Not Accept or Carry No-Cost Naloxone: Qualitative Interview Study.
Many people use opioids and are at risk of overdose. Naloxone is an opioid antagonist used to counter the effects of opioid overdose. There is an increased availability of naloxone in New York City; however, many who use opioids decline no-cost naloxone even when offered. Others may have the medication but opt not to carry it and report that they would be reluctant to administer it if they were to witness an overdose. We aim to better understand why people who use opioids may be reluctant to accept, carry, and administer naloxone, and to inform the development of messaging content that addresses barriers to its acceptance and use. We conducted formative qualitative interviews with 20 people who use opioids who are 18 years and older in New York City. Participants were recruited via key informants and chain referral. Participants cited 4 main barriers that may impede rates of naloxone acceptance, possession, and use: (1) stigma related to substance use, (2) indifference toward overdose, (3) fear of negative consequences of carrying naloxone, and (4) fear of misrecognizing the need for naloxone. Participants also offered suggestions about messaging content to tackle the identified barriers, including messages designed to normalize naloxone possession and use, encourage shared responsibility for community health, and elicit empathy for people who use drugs. Taken together, participants' narratives hold implications for the following potential messaging content: (1) naloxone is short-acting, and withdrawal sickness does not have to be long-lasting; (2) it is critical to accurately identify an opioid-involved overdose; (3) anyone can overdose; (4) naloxone cannot do harm; and (5) the prompt administration of the medication can help ensure that someone can enjoy another day. Finally, participants suggested that messaging should also debunk myths and stereotypes about people who use drugs more generally; people who use opioids who reverse overdoses should be framed as lay public health advocates and not just "others" to be managed with stigmatizing practices and language. It must be made a public health priority to get naloxone to people who use opioids who are best positioned to reverse an overdose, and to increase the likelihood that they will carry naloxone and use it when needed. Developing, tailoring, and deploying messages to address stigma, indifference toward overdose, fear and trepidation about reversing an overdose, and fear of police involvement may help alleviate fears among some people who are reluctant to obtain naloxone and use the medication on someone in an overdose situation.


Infrared fluorescent detection of PCR amplified gender identifying alleles.
An automated DNA sequencer utilizing high sensitivity infrared (IR) fluorescence technology together with Polymerase Chain Reaction (PCR) methodology was used to detect several sex differentiating loci on the X and Y chromosomes from various samples often encountered in forensic case work. Amplifications of the X-Y homologous amelogenin gene, the alpha-satellite (alphoid) repeat sequences and the X and Y chromosome zinc finger protein genes ZFX and ZFY (ZFX/ZFY) were performed. DNA extracted from various forensic specimens was amplified using either Taq, Tth or ThermoSequenase. Multiplexing using primers for all three loci in one reaction tube was achieved using Tth and ThermoSequenase. Two IR labeling strategies for detection of PCR products were utilized. In the first strategy, one of the PCR primers contained a 19-base extension at its 5' end identical to an IR-labeled universal M13 Forward (-29) primer which was included in the amplification reactions. During PCR the tailed primer generates sequence complementary to the M13 primer which subsequently primes the initial amplification products, thereby generating IR-labeled PCR products. In the second strategy, dATP labeled with an IR dye (IR-dATP) was included in the amplification reaction. During amplification IR-dATP was utilized by the polymerase and incorporated into the synthesized DNA, thus resulting in IR-labeled PCR products. X and Y specific bands were readily detected using both labeling methodologies. Amplified products were electrophoretically resolved using denaturing Long-Ranger gels and detected with an automated detection system using IR laser irradiation. A separation distance of 15 cm allowed run times of less than 2 h from sample loading to detection. Because the gels could be run more than once, at least 120 samples (2 loads x 60 samples/load) can be typed using a single gel.


When can Multi-Site Datasets be Pooled for Regression? Hypothesis Tests, ℓ 2-consistency and Neuroscience Applications.
Many studies in biomedical and health sciences involve small sample sizes due to logistic or financial constraints. Often, identifying weak (but scientifically interesting) associations between a set of predictors and a response necessitates pooling datasets from multiple diverse labs or groups. While there is a rich literature in statistical machine learning to address distributional shifts and inference in multi-site datasets, it is less clear when such pooling is guaranteed to help (and when it does not) - independent of the inference algorithms we use. In this paper, we present a hypothesis test to answer this question, both for classical and high dimensional linear regression. We precisely identify regimes where pooling datasets across multiple sites is sensible, and how such policy decisions can be made via simple checks executable on each site before any data transfer ever happens. With a focus on Alzheimer's disease studies, we present empirical results showing that in regimes suggested by our analysis, pooling a local dataset with data from an international study improves power.


Fn-EDA (Fibronectin Containing Extra Domain A) in the Plasma, but Not Endothelial Cells, Exacerbates Stroke Outcome by Promoting Thrombo-Inflammation.
Background and Purpose- Cellular Fn-EDA (fibronectin containing extra domain A) is expressed in activated endothelial cells and elevated in circulation in patients with cardiovascular diseases. Although global deficiency of Fn-EDA in mice improves stroke outcome, the specific contribution of plasma versus endothelium Fn-EDA in stroke outcome is currently unknown. We investigated the role of plasma versus endothelial Fn-EDA in stroke exacerbation in the comorbid condition of hyperlipidemia. Methods- We generated novel plasma Fn-EDA-/- ( Fn-EDA fl/fl Alb Cre) and endothelial Fn-EDA-/- ( Fn-EDA fl/fl Tie2 Cre) strains on hyperlipidemic apolipoprotein E-deficient ( ApoE-/-) background. By following the Stroke Therapy Academic Industry Roundtable guidelines, we evaluated stroke outcome in male and female mice. Susceptibility to ischemia/reperfusion injury was evaluated in 2 different models of stroke: intraluminal monofilament and embolic model on days 1, 3, and 7. Quantitative assessment of stroke outcome was evaluated by measuring infarct volume (by magnetic resonance imaging), cerebral blood flow (by laser speckle imaging), neurological and sensory-motor outcome, and postischemic thrombo-inflammation (platelet thrombi, fibrin, neutrophil, phospho-NFκB [nuclear factor κB], TNFα [tumor necrosis factor α], and IL1β [interleukin 1β]). Results- Stroke outcome was comparable in ApoE-/- Fn-EDA fl/fl Tie2 Cre and control ApoE-/- Fn-EDA fl/fl mice suggesting endothelial Fn-EDA does not contribute to stroke. ApoE-/- Fn-EDA fl/fl Alb Cre mice exhibited significantly smaller infarcts and improved neurological and sensory-motor outcome at days 1, 3, and 7 in monofilament and embolic models of stroke. Improved stroke outcome was concomitant with enhanced survival, and decreased postischemic thrombo-inflammatory response ( P<0.05 versus ApoE-/- Fn-EDA fl/fl). No sex-based differences were observed. Laser speckle imaging revealed significantly improved regional cerebral blood flow at 1 hour in ApoE-/- Fn-EDA fl/fl Alb Cre mice suggesting plasma Fn-EDA promotes postischemic secondary thrombosis. Coinfusion of anti-Fn-EDA antibody with r-tPA (recombinant tissue-type plasminogen activator) in ApoE-/- mice, 1 hour after embolization, improved stroke outcome with enhanced survival, and improved neurological outcome ( P<0.05 versus r-tPA). Conclusions- Genetic evidence suggests that plasma Fn-EDA exacerbates stroke outcome by promoting postischemic thrombo-inflammation. Interventions targeting plasma Fn-EDA may reduce brain damage after reperfusion.


Recent advances in HemN-like radical S-adenosyl-l-methionine enzyme-catalyzed reactions.
Covering: 2012 to 2019HemN-like radical S-adenosyl-l-methionine (SAM) enzymes have been recently disclosed to catalyze diverse chemically challenging reactions from primary to secondary metabolic pathways. In this highlight, we summarize the reaction examples catalyzed by HemN-like enzymes to date and the enzymatic mechanisms reported. From the recent mechanistic investigations, we reason that there is a shared initiating mechanism wherein a characteristic SAM methylene radical is proposed to abstract a hydrogen atom from an sp3 carbon or add onto an sp2 carbon center although variations occur thereafter from reaction to reaction, as well as providing a brief insight into some future prospects.


The other-race effect in perception and recognition: insights from the complete composite task.
People are more accurate at recognizing faces of their own race than faces from other races, a phenomenon known as the other-race effect. Other-race effects have also been reported in some perceptual tasks. Across 3 experiments, White and Chinese participants completed recognition tests as well as the complete paradigm of the composite task, which measures participants' abilities to selectively attend to the target region of a face while ignoring the task-irrelevant region of the face. Each task was completed with both own- and other-race faces. At a group level, participants showed significant own-race effects in recognition, but not in the composite task. At an individual difference level, the results provided no support for the hypothesis that a deficit in holistic processing for other-race faces drives the other-race effect in recognition. We therefore conclude that the other-race effect in recognition is not driven by the processes that underpin the composite effect.


Postoperative ultrasonographic appearance of uncomplicated enterotomy or enterectomy sites in dogs.
The ultrasonographic findings in 20 dogs with 25 healing enterotomy and enterectomy sites resulting from the removal of foreign material or correction of intussusceptions are presented. In this prospective study, dogs had preoperative abdominal ultrasound examinations followed by sequential sonographic examinations on the first, third, sixth, and 10th days postenterotomy or enterectomy with an additional sonographic examination after 20 days postoperatively. Documented sonographic features included length and maximal intestinal wall thickness of the enterotomy or enterectomy sites, echogenicity of omental/mesenteric fat, amount of free gas and abdominal effusion, and gastrointestinal motility. Sonographically, 57% of enterotomies and 100% of enterectomies were visualized. Pneumoperitoneum, hyperechoic omental/mesenteric fat, and abdominal effusion did not appreciably hamper evaluation of the intestinal surgical site. Absent wall layering at the surgical site was noted in 96% of dogs at day 1 postoperatively. At the final sonographic examination, wall layering remained altered to absent in 100% of dogs and normal thickness was noted in only 20% of dogs. The median maximal wall thickness was 7 and 8 mm for enterotomies and enterectomies respectively, which occurred between days 1 and 3 and days 3 and 6 postoperatively. Effusion and increased echogenicity of omental/mesenteric fat localized to the surgical site were noted in 42% and 60% of dogs respectively at day 1 postoperatively, with resolution noted between days 3 and 10 postoperatively in 92% and 80% of dogs. Generalized abdominal effusion and pneumoperitoneum were seen in 100% of dogs immediately postoperatively and resolved in 80% by day 10.


Dorsoventral patterning in hemichordates: insights into early chordate evolution.
We have compared the dorsoventral development of hemichordates and chordates to deduce the organization of their common ancestor, and hence to identify the evolutionary modifications of the chordate body axis after the lineages split. In the hemichordate embryo, genes encoding bone morphogenetic proteins (Bmp) 2/4 and 5/8, as well as several genes for modulators of Bmp activity, are expressed in a thin stripe of ectoderm on one midline, historically called "dorsal." On the opposite midline, the genes encoding Chordin and Anti-dorsalizing morphogenetic protein (Admp) are expressed. Thus, we find a Bmp-Chordin developmental axis preceding and underlying the anatomical dorsoventral axis of hemichordates, adding to the evidence from Drosophila and chordates that this axis may be at least as ancient as the first bilateral animals. Numerous genes encoding transcription factors and signaling ligands are expressed in the three germ layers of hemichordate embryos in distinct dorsoventral domains, such as pox neuro, pituitary homeobox, distalless, and tbx2/3 on the Bmp side and netrin, mnx, mox, and single-minded on the Chordin-Admp side. When we expose the embryo to excess Bmp protein, or when we deplete endogenous Bmp by small interfering RNA injections, these expression domains expand or contract, reflecting their activation or repression by Bmp, and the embryos develop as dorsalized or ventralized limit forms. Dorsoventral patterning is independent of anterior/posterior patterning, as in Drosophila but not chordates. Unlike both chordates and Drosophila, neural gene expression in hemichordates is not repressed by high Bmp levels, consistent with their development of a diffuse rather than centralized nervous system. We suggest that the common ancestor of hemichordates and chordates did not use its Bmp-Chordin axis to segregate epidermal and neural ectoderm but to pattern many other dorsoventral aspects of the germ layers, including neural cell fates within a diffuse nervous system. Accordingly, centralization was added in the chordate line by neural-epidermal segregation, mediated by the pre-existing Bmp-Chordin axis. Finally, since hemichordates develop the mouth on the non-Bmp side, like arthropods but opposite to chordates, the mouth and Bmp-Chordin axis may have rearranged in the chordate line, one relative to the other.


[Toward a model of communications in public health in Latin America and the Caribbean].
So far, there have been no bibliometric or scientometric studies that make it possible to examine, with quantitative, retrospective, and comprehensive criteria, the scientific output on public health in Latin America and the Caribbean (LAC). Further, the weakness of the existing information systems makes it impossible to examine the relevance, quality, and impact of this scientific output, with a view to evaluating it in terms of societal needs and existing patterns of scientific communication. This article presents the results of a bibliographic analysis of the scientific output in the area of public health in Latin America and the Caribbean. The ultimate goal of the analysis is to build a model of scientific communication in this field, to help researchers, managers, and others working in the area of public health to make decisions and choose actions to take. We conducted a literature review in order to identify the distribution of publications on public health that were produced by LAC researchers and published in each of the LAC countries from 1980 through 2002. The review used the Literatura Latino-Americana e do Caribe em Saúde Pública (LILACS-SP) (Latin American and Caribbean Literature on Public Health) bibliographic database. That database is operated by the Latin American and Caribbean Center on Health Sciences Information (BIREME), which is in São Paulo, Brazil. We processed the LILACS-SP data using two software packages, Microsoft Excel and Bibexcel, to obtain indicators of the scientific output, the type of document, the language, the number of authors for each publication, the thematic content, and the participating institutions. For the 1980-2002 period, there were 97,605 publications registered, from a total of 37 LAC countries. For the analysis presented in this article, we limited the sample to the 8 countries in Latin America and the Caribbean that had at least 3,000 documents each registered in the LILACS-SP database over the 1980-2002 study period. In descending order of the number of publications registered, the 8 nations were: Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Peru, and Venezuela. Those 8 countries were responsible for 83,054 publications (85.10% of the total of 97,605 registered documents produced by the 37 LAC countries). Of those 83,054 publications from the 8 countries, 56,253 of them (67.73%) were articles published in scientific journals and 24,488 were monographs (29.48%). The proportion of works produced by two or more coauthors was relatively high (56.48%). The 56,253 articles appeared in a total of 929 different journals. Of the 929 journals, 91 of them published at least 150 articles over the study period. In descending order, LAC journals with the largest number of articles on public health were: Revista de Saúde Pública (Brazil); Cadernos de Saúde Pública (Brazil); Revista Médica de Chile; Archivos Latinoamericanos de Nutrición (Venezuela); and Salud Pública de México. The 91 journals that published at least 150 articles represented 29 different specialties. The most common of the specialties for the 91 journals were general medicine (18 journals) and pediatrics (10 journals). In descending order, the populations that the publications dealt with primarily were human beings in general, females, males, and adults; and, in descending order, a relatively small number of publications dealt with pregnant women and middle-aged or elderly persons. The topics most often covered in the publications were risk factors, health policy, and primary health care, as well as family doctors in the case of Cuba. This research produced a preliminary model of communications in public health in LAC countries that will hopefully help lay the groundwork for further research to develop a model of scientific communication in LAC nations.


Specificity and properties of the nucleotide carrier in chromaffin granules from bovine adrenal medulla.
1. The influence of various substances on the uptake of [3H]ATP and [14C]-noradrenaline into isolated bovine chromaffin granules was investigated. The carrier-mediated [3H]ATP uptake is specifically inhibited by SO42-, PO43- and phosphoenolpyruvate. Compounds with carboxylic acid or sulphonic acid groups had no significant inhibitory effects on either uptake. 2. 35SO42-, 32PO43- and phosphoenol[14C]pyruvate are taken up into chromaffin granules by a temperature-dependent process that is inhibited by atractyloside, uncouplers of oxidative phosphorylation and lipid-permeant anions. The apparent Km of 35SO42- uptake is 0.4 mM. 3. These results indicate that the nucleotide carrier in chromaffin granules has a broad specificity, transporting compounds with two strong negative charges. 4. Amino acid probes influence the uptake of ATP and catecholamines differently. Pyridoxal phosphate inhibits both uptake processes, 4,4'-di-isothiocyanostilbene-2,2'-disulphonic acid preferentially blocks ATP uptake, whereas phenylglyoxal blocks only ATP transport. It is suggested that the nucleotide carrier possesses arginine residues in a functionally important position. 5. The significance of these results obtained on isolated granules for the function of chromaffin granules within the cell is discussed.


Pushing typists back on the learning curve: contributions of multiple linguistic units in the acquisition of typing skill.
The present study investigated the way people acquire and control skilled performance in the context of typewriting. Typing skill was degraded by changing the location of a key (target key) while retaining the locations of other keys to disable an association between the letter and the key. We conducted 4 experiments: Experiment 1 demonstrated that disabling a letter-key association affected not only the execution of the target keystroke but also the planning of other keystrokes for words involving the target key. In Experiments 2-4, typists practiced with a new target location and then transferred to a condition in which they typed the practiced words with the original key location (Experiment 2) or typed new words with the practiced key location (Experiments 3 and 4). Experiment 2 showed that the newly acquired letter-key association interfered with the execution of the original keystroke but not planning. Experiments 3 and 4 demonstrated that acquisition of the new letter-key association depended on multiple levels of linguistic units. Experiment 4 demonstrated that acquisition of the new association depended on sequences both before and after the target keystroke. We discuss implications of the results for 2 prominent approaches to modeling sequential behavior: hierarchical control and recurrent network models.


Training affects muscle phospholipid fatty acid composition in humans.
Training improves insulin sensitivity, which in turn may affect performance by modulation of fuel availability. Insulin action, in turn, has been linked to specific patterns of muscle structural lipids in skeletal muscle. This study investigated whether regular exercise training exerts an effect on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 +/- 0.5% and 3.2 +/- 0.4% of total fatty acids, respectively) than the untrained leg (8.8 +/- 0.5% and 2.6 +/- 0.4%, P < 0.05). The ratio between n-6 and n-3 fatty acids was significantly lower in the trained (11.1 +/- 0.9) than the untrained leg (13.1 +/- 1.2, P < 0.05). In contrast, training did not affect muscle triacylglycerol fatty acid composition. Citrate synthase activity was increased by 17% in the trained compared with the untrained leg (P < 0.05). In this model, diet plays a minimal role, as the influence of dietary intake is similar on both legs. Regular exercise training per se influences the phospholipid fatty acid composition of muscle membranes but has no effect on the composition of fatty acids stored in triacylglycerols within the muscle.


Troponin I Mutations R146G and R21C Alter Cardiac Troponin Function, Contractile Properties, and Modulation by Protein Kinase A (PKA)-mediated Phosphorylation.
Two hypertrophic cardiomyopathy-associated cardiac troponin I (cTnI) mutations, R146G and R21C, are located in different regions of cTnI, the inhibitory peptide and the cardiac-specific N terminus. We recently reported that these regions may interact when Ser-23/Ser-24 are phosphorylated, weakening the interaction of cTnI with cardiac TnC. Little is known about how these mutations influence the affinity of cardiac TnC for cTnI (KC-I) or contractile kinetics during β-adrenergic stimulation. Here, we tested how cTnI(R146G) or cTnI(R21C) influences contractile activation and relaxation and their response to protein kinase A (PKA). Both mutations significantly increased Ca(2+) binding affinity to cTn (KCa) and KC-I. PKA phosphorylation resulted in a similar reduction of KCa for all complexes, but KC-I was reduced only with cTnI(WT). cTnI(WT), cTnI(R146G), and cTnI(R21C) were complexed into cardiac troponin and exchanged into rat ventricular myofibrils, and contraction/relaxation kinetics were measured ± PKA phosphorylation. Maximal tension (Tmax) was maintained for cTnI(R146G)- and cTnI(R21C)-exchanged myofibrils, and Ca(2+) sensitivity of tension (pCa50) was increased. PKA phosphorylation decreased pCa50 for cTnI(WT)-exchanged myofibrils but not for either mutation. PKA phosphorylation accelerated the early slow phase relaxation for cTnI(WT) myofibrils, especially at Ca(2+) levels that the heart operates in vivo. Importantly, this effect was blunted for cTnI(R146G)- and cTnI(R21C)-exchanged myofibrils. Molecular dynamics simulations suggest both mutations inhibit formation of intra-subunit contacts between the N terminus and the inhibitory peptide of cTnI that is normally seen with WT-cTn upon PKA phosphorylation. Together, our results suggest that cTnI(R146G) and cTnI(R21C) blunt PKA modulation of activation and relaxation kinetics by prohibiting cardiac-specific N-terminal interaction with the cTnI inhibitory peptide.


Strategies for Postoperative Seroma Prevention: A Systematic Review.
There is conflicting evidence on the effectiveness of the various strategies to prevent postoperative seroma. Many high-quality studies have been performed to evaluate those strategies, but the numbers of patients included in those studies have been small. The authors' goal was to perform a systematic review of all Level I and II studies on the prevention of postoperative seroma. A PubMed search was performed of all Level I and II studies that evaluated strategies for the prevention of postoperative seroma. Only English-language comparative studies on humans, defining seroma as a postoperative serous fluid collection detectable on physical examination, were included. Data from all the studies were compiled, and a systematic review was performed to evaluate the effectiveness of each strategy. Seventy-five studies comprising 7173 patients were included. Effective strategies for seroma prevention included the use of closed-suction drains; keeping the drains until their output volume was minimal; maintaining a high pressure gradient in the drains; using sharp or ultrasonic dissection rather than cautery; dissecting the abdomen in a place superficial to the Scarpa fascia; ligating blood vessels with sutures or clips; using quilting or progressive tension sutures; using fibrin, thrombin, or talc; and immobilizing the surgical site postoperatively. Surgical-site compression did not prevent seroma accumulation. The use of sclerosants at the initial operation actually increased the risk of seroma. Seroma is a common and frustrating complication in plastic surgery. This study demonstrates that simple strategies can be used to lower the risk of seroma. Therapeutic, II.


Using hippocampal-striatal loops for spatial navigation and goal-directed decision-making.
The hippocampus plays a central role in spatial representation, declarative and episodic memory. In this area, so-called place cells possess high spatial selectivity, firing preferentially when the individual is within a small area of the environment. Interestingly, it has been found in rats that these cells can be active also when the animal is outside the location or context of their corresponding place field producing so-called "forward sweeps". These typically occur at decision points during task execution and seem to be utilized, among other things, for the evaluation of potential alternative paths. Anticipatory firing is also found in the ventral striatum, a brain area that is strongly interconnected with the hippocampus and is known to encode value and reward. In this paper, we describe a biologically based computational model of the hippocampal-ventral striatum circuit that implements a goal-directed mechanism of choice, with the hippocampus primarily involved in the mental simulation of possible navigation paths and the ventral striatum involved in the evaluation of the associated reward expectancies. The model is validated in a navigation task in which a rat is placed in a complex maze with multiple rewarding sites. We show that the rat mentally activates place cells to simulate paths, estimate their value, and make decisions, implementing two essential processes of model-based reinforcement learning algorithms of choice: look-ahead prediction and the evaluation of predicted states.


Alterations in physiological functions and in brain monoamine content in the sympathectomized rats.
In the present study, we conducted pre-ganglionic decentralization (or sympathetic trunk resection) of the superior cervical ganglia and observed alterations in several physiological functions and in the monoamine content of different brain regions. Over an ambient temperature range of 8-30 degrees C, these sympathectomized rats maintained their rectal temperatures within a normal limit displayed by the intact controls. These sympathectomized animals, although showing no change in the level of spontaneous pain threshold or motor activity, did display an increased sensitivity of analgesic responses to morphine administration or locomotor stimulant responses to amphetamine administration. Biochemical examination revealed that these sympathectomized animals had a higher level of norepinephrine, dopamine or 5-hydroxytryptamine in the hypothalamus, as well as a higher level of dopamine in the corpus striatum. However, in the brainstem, these sympathectomized animals had a unaltered monoamine level. The data indicate that, in a sympathectomized condition, changes in the monoamine content of different brain regions may be correlated with the above-mentioned alterations in somatosensory and motor neural functions.


A step forward in studying the compact genetic algorithm.
The compact Genetic Algorithm (cGA) is an Estimation of Distribution Algorithm that generates offspring population according to the estimated probabilistic model of the parent population instead of using traditional recombination and mutation operators. The cGA only needs a small amount of memory; therefore, it may be quite useful in memory-constrained applications. This paper introduces a theoretical framework for studying the cGA from the convergence point of view in which, we model the cGA by a Markov process and approximate its behavior using an Ordinary Differential Equation (ODE). Then, we prove that the corresponding ODE converges to local optima and stays there. Consequently, we conclude that the cGA will converge to the local optima of the function to be optimized.


Introducing novel type of human DNA markers for forensic tissue identification: DNA copy number variation allows the detection of blood and semen.
Establishing the cellular or tissue-type origin of human biological traces found at crimes scenes is forensically relevant, as it allows evaluating the crime relevance of such traces and enables reconstructing the sequence of crime events. Messenger RNA and micro RNA markers are useful for forensic tissue identification, but provide challenges for linking RNA-identified cell/tissue types with DNA-identified trace donors, especially in mixed traces. DNA methylation markers overcome this problem, but provide technical challenges due to the DNA treatment required by most analysis methods. Here we introduce a novel type of DNA markers for forensic tissue identification analysed without prior DNA treatment, namely copy number variation (CNV). Using genome-wide CNV screening followed-up by targeted qPCR confirmation, and using qPCR analysis of additional CNV-like candidate DNA markers, in samples of several individuals from all commonly encountered forensically-relevant tissue types, we identified DNA markers specific for blood and semen, respectively. Preliminary forensic validation testing demonstrates that the developed qPCR assays are highly sensitive - delivering positive results down to picogram level of input DNA, specific, and can cope well with degraded DNA, providing suitable prerequisites for forensic applications. Moreover, we exemplified that using the CNV qPCR products as input material for subsequent forensic STR analysis delivered full STR profiles, opening-up new avenues of using the same DNA aliquot for both forensic purposes, tissue and individual identification. Provided additional forensic validation studies, we envision the application of these novel DNA markers for forensic tissue identification in future forensic casework. Such CNV markers are particularly useful for tissue identification in old/cold cases, where aged/old DNA extracts are available that contain no RNA and are not suitable for DNA methylation analysis due to limited DNA quantity and quality.


The evaluation of complex clinical trial protocols: resources available to research ethics committees and the use of clinical trial registries--a case study.
To assess the potential role of clinical trial (CT) registries and other resources available to research ethics committees (RECs) in the evaluation of complex CT protocols in low-income and middle-income countries. Using a case study approach, the authors examined the decision-making process of a REC in Argentina and its efforts to use available resources to decide on a complex protocol. We also analysed the information in the USA and other CT registries and consulted 24 CT experts in seven countries. Information requested by the Argentinean REC from other national RECs and ethics' experts was not useful to verify the adequacy of the REC's decision whether or not to approve the CT. The responses from the national regulatory agency and the sponsor were not helpful either. The identification of international resources that could assist was beyond the REC's capability. The information in the USA and other CT registries is limited, and at times misleading; and its accuracy is not verified by register keepers. RECs have limited access to experts and institutions that could assist them in their deliberations. Sponsors do not always answer RECs' request for information to properly conduct the ethical and methodological assessment of CT protocols. The usefulness of the CT registries is curtailed by the lack of appropriate codes and by data errors. Information about reasons for rejection, withdrawal or suspension of the trial should be included in the registries. Establishing formal channels of communication among national and foreign RECs and with independent international reference centres could strengthen the ethical review of CT protocols.


Nanofocusing of radially polarized light with dielectric-metal-dielectric probe.
Nanofocusing properties of a tip in the form of a dielectric tapered fiber with metal apertureless coating and dielectric nanocladding can be tuned within a wide spectral range by choice of cladding permittivity. The silica core of diameter decreasing from 2 mum to 5 nm in apex is covered with a silver layer and has a 5 nm dielectric cladding. Internal illumination with a radially polarized Laguerre-Gauss beam guided in fiber is used. In body-of-revolution finite-difference time-domain simulations we find that with an increase of the refractive index of nanocladdings the maximum enhancement occurs for increasingly longer wavelengths.