Effect of a promotional campaign on heart-healthy menu choices in community restaurants.
The research question examined in this study was: Does a promotional campaign impact the sales of heart-healthy menu items at community restaurants? The 8-week promotional campaign used professionally developed advertisements in daily and monthly print publications and posters and table tents in local restaurants. Nine restaurants tracked the sales of selected heart-healthy menu items and comparable menu items sold before and after a promotional campaign. The percentage of heart-healthy items sold after the campaign showed a trend toward a slight increase in heart-healthy menu item selections, although it was not statistically significant. This study and others indicate that dietetics professionals must continue to develop strategies to promote heart-healthy food choices in community restaurants.


The Violent Content in Attenuated Psychotic Symptoms.
The relationship between psychosis and violence has typically focused on factors likely to predict who will commit violent acts. One unexplored area is violence in the content of subthreshold positive symptoms. The current aim was to conduct an exploratory analysis of violent content in the attenuated psychotic symptoms (APS) of those at clinical high risk of psychosis (CHR) who met criteria for attenuated psychotic symptom syndrome (APSS). The APS of 442 CHR individuals, determined by the Structured Interview for Prodromal Syndromes, were described in comprehensive vignettes. The content of these symptoms were coded using the Content of Attenuated Positive Symptoms Codebook. Other measures included clinical symptoms, functioning, beliefs and trauma. Individuals with violent content had significantly higher APS, greater negative beliefs about the self and others, and increased bullying. The same findings and higher ratings on anxiety symptoms were present when participants with self-directed violence were compared to participants with no violent content. Individuals reporting violent content differ in their clinical presentation compared to those who do not experience violent content. Adverse life events, like bullying, may impact the presence of violent content in APS symptoms. Future studies should explore violent content in relation to actual behavior.


Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice.
Brown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.


An evidence-based catheter bundle alters central venous catheter strategy in newborn infants.
To assess whether introduction of an evidence-based percutaneously inserted central catheter (PICC) care bundle reduced the risk of central line-associated bloodstream infection (CLABSI), thus altering the comparative risk of CLABSI in infants. This retrospective cohort study included all infants for whom an umbilical venous catheter (UVC) was placed as part of routine care between Jan 1, 2006, and Dec 31, 2009, a period during which standardized PICC insertion and care bundles were introduced. Duration of UVC use was divided in ≤ 7 days and >7 days. Infants in the ≤ 7 days UVC group had 1.0 CLABSI/1000 catheter days, and infants in the >7 days UVC group had 4.0 CLABSI/1000 catheter days (P < .001). Controlling for birth weight, gestational age, and antibiotic use, the >7 days UVC group had a greater risk of CLABSI (OR, 5.48) than the ≤ 7 days UVC group. CLABSI rate increased more rapidly in UVC than PICC with increasing duration of catheter rose. Replacement of a UVC with a PICC when central venous access is needed after 7 days of age may reduce CLABSI.


An objective comparison of transurethral resection and bladder neck incision in the treatment of prostatic hypertrophy.
Transurethral resection has become the operation of choice in almost all cases of benign prostatic enlargement. However, when the gland does not exceed 30 gm. bladder neck incision is easier to perform, results in a lower morbidity, and is less likely to be followed by incontinence and retrograde ejaculation. We studied 2 groups of men with proved obstruction. Complete urodynamic investigation was done on 51 patients before and on 44 patients after the operation. We compared our subjective and objective findings in the 2 groups. The conclusion suggest that bladder neck incision is as effective as transurethral resection in relieving the obstruction of prostatic enlargement in the presence of a small gland.


It's Not Only Who You Are but Who You Are With: High School Composition and Individuals' Attainment Over the Life Course.
We examined life-course effects of attending selective schools using a longitudinal study of U.S. high school students begun in 1960 ( Ns ranging from 1,952 to 377,015). The effects, measured 11 and 50 years after the initial assessment, differed significantly across the two indicators of school selectivity that were used. School average socioeconomic background was positively related to students' educational expectations, educational attainment, income, and occupational prestige at the 11-year follow-up (0.15 ≤ β ≤ 0.39; all ps < .001). Conversely, schools' average achievement at the 11-year follow-up was negatively related to students' expectations, attainment, income, and occupational prestige (-0.42 ≤ β ≤ -0.05; all ps < .05) when schools' socioeconomic background was controlled for. All associations were mediated by students' educational expectations. With the exception of income, these effects were consistent 50 years after high school, pointing to the long reach of beneficial learning resources and negative social comparison processes when attending selective schools.


Imaging the polymerization of multivalent nanoparticles in solution.
Numerous mechanisms have been studied for chemical reactions to provide quantitative predictions on how atoms spatially arrange into molecules. In nanoscale colloidal systems, however, less is known about the physical rules governing their spatial organization, i.e., self-assembly, into functional materials. Here, we monitor real-time self-assembly dynamics at the single nanoparticle level, which reveal marked similarities to foundational principles of polymerization. Specifically, using the prototypical system of gold triangular nanoprisms, we show that colloidal self-assembly is analogous to polymerization in three aspects: ensemble growth statistics following models for step-growth polymerization, with nanoparticles as linkable "monomers"; bond angles determined by directional internanoparticle interactions; and product topology determined by the valency of monomeric units. Liquid-phase transmission electron microscopy imaging and theoretical modeling elucidate the nanometer-scale mechanisms for these polymer-like phenomena in nanoparticle systems. The results establish a quantitative conceptual framework for self-assembly dynamics that can aid in designing future nanoparticle-based materials.Few models exist that describe the spontaneous organization of colloids into materials. Here, the authors combine liquid-phase TEM and single particle tracking to observe the dynamics of gold nanoprisms, finding that nanoscale self-assembly can be understood within the framework of atomic polymerization.


The Effect of Restricting Residents' Duty Hours on Patient Safety, Resident Well-Being, and Resident Education: An Updated Systematic Review.
Despite 25 years of implementation and a sizable amount of research, the impact of resident duty hour restrictions on patients and residents still is unclear. Advocates interpret the research as necessitating immediate change; opponents draw competing conclusions. This study updates a systematic review of the literature on duty hour restrictions conducted 1 year prior to the implementation of the Accreditation Council for Graduate Medical Education's 2011 regulations. The review draws on reports catalogued in MEDLINE and PreMEDLINE from 2010 to 2013. Interventions that dealt with the duty hour restrictions included night float, shortened shifts, and protected time for sleep. Outcomes were patient care, resident well-being, and resident education. Studies were excluded if they were not conducted in patient care settings. Twenty-seven studies met the inclusion criteria. Most frequently, the studies concluded that the restrictions had no impact on patient care (50%) or resident wellness (47%), and had a negative impact on resident education (64%). Night float was the most frequent means of implementing duty hour restrictions, yet it yielded the highest proportion of unfavorable findings. This updated review, including 27 recent applicable studies, demonstrates that focusing on duty hours alone has not resulted in improvements in patient care or resident well-being. The added duty hour restrictions implemented in 2011 appear to have had an unintended negative impact on resident education. New approaches to the issue of physician fatigue and its relationship to patient care and resident education are needed.


Interferon-beta expressed by a rabies virus-based HIV-1 vaccine vector serves as a molecular adjuvant and decreases pathogenicity.
Type I interferon is important in anti-viral responses and in coordinating the innate immune response. Here we explore the use of interferon-beta to adjuvant the response to a rabies virus (RV) vaccine vector expressing both HIV-1 Gag and IFN-beta. Viral load and immune responses of immunized mice were analyzed over time. Our results indicate that the RV expressing IFN-beta (IFN+) is highly attenuated when compared to control RV and demonstrate that the expression of IFN-beta reduces viral replication approximately 100-fold. Despite the decrease in replication, those mice immunized with the IFN+ RV had a significantly greater number of activated CD8+ T cells. The increased activation of CD8+ T cells was dependent on IFN-beta signaling, as we saw no difference following infection of IFNAR-/- mice. Although mice immunized with IFN+ have a greater primary immune response than controls, immunized mice that were challenged with vaccinia-expressing Gag had no significant difference in the number or functionality of CD8+ T cells. The increased CD8+ T cell activation in the presence of IFN-beta, even with greatly reduced viral replication, indicates the beneficial effect of IFN-beta for the host.


Brassinosteroid coordinates cell layer interactions in plants via cell wall and tissue mechanics.
Growth coordination between cell layers is essential for development of most multicellular organisms. Coordination may be mediated by molecular signaling and/or mechanical connectivity between cells, but how genes modify mechanical interactions between layers is unknown. Here we show that genes driving brassinosteroid synthesis promote growth of internal tissue, at least in part, by reducing mechanical epidermal constraint. We identified a brassinosteroid-deficient dwarf mutant in the aquatic plant Utricularia gibba with twisted internal tissue, likely caused by mechanical constraint from a slow-growing epidermis. We tested this hypothesis by showing that a brassinosteroid mutant in Arabidopsis enhances epidermal crack formation, indicative of increased tissue stress. We propose that by remodeling cell walls, brassinosteroids reduce epidermal constraint, showing how genes can control growth coordination between layers by means of mechanics.


Anaerobic oxidation of methane in terrestrial wetlands: The rate, identity and metabolism.
The recent discovery of anaerobic oxidation of methane (AOM) in freshwater ecosystems has caused a great interest in "cryptic methane cycle" in terrestrial ecosystems. Anaerobic methanotrophs appears widespread in wetland ecosystems, yet, the scope and mechanism of AOM in natural wetlands remain poorly understood. In this paper, we review the recent progress regarding the potential of AOM, the diversity and distribution, and the metabolism of anaerobic methanotrophs in wetland ecosystems. The potential of AOM determined through laboratory incubation or in situ isotopic labeling ranges from 1.4 to 704.0 nmol CH4·g-1 dry soil·d-1. It appears that the availability of electron acceptors is critical in driving different AOM in wetland soils. The environmental temperature and salinity exert a significant influence on AOM activity. Reversal methanogenesis and extracellular electron transfer are likely involved in the AOM process. In addition to anaerobic methanotrophic archaea, the direct involvement of methanogens in AOM is also probable. This review presented an overview of the rate, identity, and metabolisms to unravel the biogeochemical puzzle of AOM in wetland soils.


Copper-catalyzed three-component synthesis of aminonaphthoquinone-sulfonylamidine conjugates and in vitro evaluation of their antiproliferative activity.
A series of aminonaphthoquinone-sulfonylamidine conjugates were synthesized via a copper-catalyzed three-component reaction of N-propargyl aminonaphthoquinone, sulfonyl azides and various amines. Majority of the compounds exhibited promising antiproliferative potential when evaluated against a panel of four cancer cell lines. Docking experiments of representative compounds indicated that the conjugates can occupy the ATP-binding pocket of topoisomerase-II enzyme.


Expression of the androgen receptor and 5 alpha-reductase type 2 in the developing human fetal penis and urethra.
Normal penile development is dependent on testosterone, its conversion via steroid 5 alpha-reductase type 2 to dihydrotestosterone, and a functional androgen receptor (AR). The goal of this study was to investigate the distribution of AR and 5 alpha-reductase type 2 in the developing human fetal external genitalia with special emphasis on urethra formation. Twenty fetal genital specimens from normal human males (12-20 weeks gestation) were sectioned serially and stained by avidin-biotinylated peroxidase complex method with antigen retrieval. Stained sections throughout male genital development documented the expression of AR and 5 alpha-reductase type 2 in the phallus. Between 12 and 14 weeks of gestation, AR was localized to epithelial cells of the urethral plate in the glans, the tubular urethra of the penile shaft, and stromal tissue surrounding the urethral epithelium. In the fetal penis between 16 and 20 weeks gestation, the density of AR expression was greatest in urethral epithelial cells versus the surrounding stromal tissues. There was a characteristic pattern of AR expression in the glandular urethral epithelium between 16 and 20 weeks gestation. AR expression was greater along the ventral aspect of the glandular urethra than along the dorsal aspect of the urethral epithelium. The expression of 5 alpha-reductase type 2 was localized to the stroma surrounding the urethra, especially along the urethral seam area in the ventral portion of the remodeling urethra. These anatomical studies support the hypothesis that androgens are essential for the formation of the ventral portion of the urethra and that abnormalities in either the AR or 5 alpha-reductase type 2 can explain the occurrence of hypospadias.


Calcium signaling pathway involving calcineurin regulates interleukin-8 gene expression through activation of NF-kappaB in human osteoblast-like cells.
Involvement of aberrant IL-8 production by osteoblasts was demonstrated in pathogenesis of inflammatory joint diseases. We thus investigated intracellular signaling pathways leading to IL-8 expression in human osteoblast-like HOS-TE85 cells. It was demonstrated that Ca2+ signaling pathway involving calcineurin regulates IL-8 gene expression through activation of a transcription factor, NF-kappaB. Involvement of aberrant interleukin (IL)-8 production by osteoblasts was demonstrated in pathogenesis of inflammatory joint diseases. However, intracellular signaling pathways leading to IL-8 expression in osteoblasts have been poorly explored. Because a variety of external stimuli was shown to increase intracellular Ca2+ in osteoblasts, we investigated effects of Ca(2+)-ionophore and phorbol-myristate-acetate (Ion/PMA) on IL-8 expression in human osteoblast-like HOS-TE85 cells and compared the effects with those elicited by TNF-alpha. HOS-TE85 cells were treated with Ion/PMA or TNF-alpha in the presence and absence of calcineurin inhibitors (CnI), cyclosporin A, and FK506. IL-8 mRNA levels and its promoter activities were examined by Northern blot and luciferase reporter analyses, respectively. Electrophoretic mobility shift assay (EMSA) was used to evaluate DNA binding activities of transcription factors such as NF-kappaB. Degradation of IkappaB, a cytoplasmic NF-kappaB-inhibitory protein, was examined by Western blot analysis. Ion/PMA and TNF-alpha induced IL-8 mRNA expression. Interestingly, CnI attenuated the induction by Ion/PMA, but not that by TNF-alpha. Promoter activity was also increased by both stimuli, and only the Ion/PMA-dependent increase was suppressed by CnI. Introduction of mutations in the promoter demonstrated that one NF-kappaB site was responsible for the suppression by CnI. EMSA revealed that this site binds with NF-kappaB containing p65 that was activated by Ion/PMA and TNF-alpha and that CnI inhibited only Ion/PMA-dependent NF-kappaB activation. Accordingly, CnI blocked only Ion/PMA-dependent degradation of IkappaB-alpha. In addition, the basal and Ion/PMA-dependent IL-8 promoter activities were enhanced by co-transfection of constitutively active calcineurin. These results show that the Ca2+ signaling pathway involving calcineurin regulates IL-8 gene expression through activation of NF-kappaB in human osteoblast-like cells.


Mycotoxicoses of animals.
Mycotoxicoses are intoxications caused by ingestions of foodstuffs contaminated with mycotoxins, i.e. toxic secondary metabolites of microscopic filamentous fungi (moulds). By field observations and by experimental testing, toxins or toxic strains of more than 100 species of fungi have been encountered. However, causal associations have so far only been established for a small number of mycotoxicoses in farm animals, and the more important mycotoxicoses are aflatoxicosis, facial eczema, mycotoxic nephropathy, and estrogenic syndrome. A full assessment of the impact of mycotoxins on the health of farm animals can hardly be made at present, because the amount of surveillance data from mycotoxicoses is very limited, due mainly to inadequate diagnostic criteria. A new set of criteria for the diagnosis of mycotoxicosis is proposed, which has been successfully applied in the causative study of mycotoxic porcine nephropathy.


Evidence of variant intra- and interspecific scaling of tree crown structure and relevance for allometric theory.
General scaling rules or constants for metabolic and structural plant allometry as assumed by the theory of Euclidian geometric scaling (2/3-scaling) or metabolic scaling (3/4-scaling) may meet human's innate propensity for simplicity and generality of pattern and processes in nature. However, numerous empirical works show that variability of crown structure rather than constancy is essential for a tree's success in coping with crowding. In order to link theory and empiricism, we analyzed the intra- and inter-specific scaling of crown structure for 52 tree species. The basis is data from 84 long-term plots of temperate monospecific forests under survey since 1870 and a set of 126 yield tables of angiosperm and gymnosperm forest tree species across the world. The study draws attention to (1) the intra-specific variation and correlation of the three scaling relationships: tree height versus trunk diameter, crown cross-sectional area versus trunk diameter, and tree volume versus trunk diameter, and their dependence on competition, (2) the inter-specific variation and correlation of the same scaling exponents ([Formula: see text] and [Formula: see text]) across 52 tree species, and (3) the relevance of the revealed variable scaling of crown structure for leaf organs and metabolic scaling. Our results arrive at suggesting a more extended metabolic theory of ecology which includes variability and covariation between allometric relationships as prerequisite for the individual plant's competitiveness.


Pseudophakic retinal detachment: anatomic and visual results.
Our purpose was to report the anatomic and visual results of pseudophakic retinal detachment surgery in a large series of consecutive cases and to analyze the risk factors for anatomic and functional failure. This retrospective study covered 290 primary cases of idiopathic rhegmatogenous retinal detachment operated on by the same surgeon during an 8-year period. Data relating to 26 pre-, per-, and postoperative variables were studied. For the statistical analyses we used both Chi-square and stepwise logistic regression tests. Vitreous loss occurred in 56 cases (19.3%), and the retina detached more than 2 years after lens extraction in 108 cases (37.2%). Breaks could be identified in 249 cases (85.8%), and the macula was involved in 235 (81%). The overall reattachment rate was 85.2% (247/290), and a postoperative visual acuity of 0.5 D or more was attained in 49.6% of cases (144/290). We found no difference between phakoemulsification, extracapsular, intracapsular techniques or between anterior chamber, posterior chamber, iris-fixated lenses as regards anatomic and functional outcomes. Proliferative vitreoretinopathy (PVR) and photoreceptor dysfunction were the main causes of anatomic and functional failure respectively. We identified extensive detachment, preoperative choroidal detachment, intraoperative hemorrhage and surgery for PVR as predictors of anatomic failure, while preoperative inflammation, preoperative PVR of grade B or worse, and surgery for PVR were predictors of functional failure. In this series, anatomic and visual results of reattachment surgery were much more affected by detachment features and by PVR than by the techniques and complications of cataract surgery.


Pain coping profiles in adolescents with chronic pain.
This study sought to evaluate the extent to which the pain coping profiles observed by Walker and colleagues in a sample of patients with chronic abdominal pain also were evident in a sample of adolescent patients who presented to a tertiary care clinic for evaluation of a variety of diverse pain conditions. In addition, we aimed to evaluate the relation of these pain coping profiles to patients' emotional and physical functioning. Participants (n=254) were adolescent patients aged 12-17 years. Patients completed the Pain Response Inventory (PRI) as well as measures of pain, somatic symptoms, anxiety and depressive symptoms, and functional disability. Using the PRI classification algorithm developed by Walker and colleagues, we successfully classified all the patients in our sample. We also found that the pain coping profiles successfully differentiated among patients with different levels of symptoms, disability, and emotional distress, further demonstrating the external validity of these profiles. Results have implications for tailoring pain treatment interventions to patients' particular coping profiles.


The influence of cisplatinum and goserelinum on the magnesium and calcium level in rat serum.
The influence of cisplatinum and goserelinum on the magnesium and calcium concentration in rat serum has been studied. The cisplatinum induces decrease in serum magnesium concentration (to 70%), and calcium concentration (to 63%). Goserelinum activity was similar to cisplatinum activity. The magnesium concentration decreased to 60%, and calcium to 44%. In condition of cisplatinum and goserelinum activity the hypomagnesemia and hypocalcemia were noted.


Feasibility of a 26-Week Exercise Program to Improve Brain Health in Older Adults at Risk for Type 2 Diabetes: A Pilot Study.
Older adults at risk for type 2 diabetes (i.e. overweight individuals or those with prediabetes) experience accelerated cognitive and brain deficits. Aerobic training is known to improve these deficits, but the effects of resistance training are relatively unknown. Before conducting a large-scale, randomized, controlled trial to assess the effects of resistance training, we first conducted a pilot feasibility study to examine recruitment, attendance and retention rates in this population. Program participants (aged 60 to 80 years, mean age 68.7±5.7 years, 50% females) at risk for type 2 diabetes (body mass index of ≥25 or fasting blood glucose of 6.1 to <7 mmol/L) underwent 26 weeks of thrice-weekly progressive resistance training (n=13) or balance-and-tone exercises (control group, n=11). Recruitment, attendance and retention rates were recorded, and study feedback from program participants and research assistants was collected via questionnaires. We recruited 72 older adults (total number enrolled = 24) over 17 months. Program retention and attendance were 95.8% and 84.4%, respectively. Program participants and research assistants expressed a high level of study enjoyment, and suggestions on how to improve study procedures were provided. Based on our findings, a large-scale study in this at-risk group of older adults is feasible, and key strategies to improving future trials were identified.


Successful transmission of Solenopsis invicta virus 3 to Solenopsis invicta fire ant colonies in oil, sugar, and cricket bait formulations.
Tests were conducted to evaluate whether Solenopsis invicta virus 3 (SINV-3) could be delivered in various bait formulations to fire ant colonies and measure the corresponding colony health changes associated with virus infection in Solenopsis invicta. Three bait formulations (10% sugar solution, cricket paste, and soybean oil adsorbed to defatted corn grit) effectively transmitted SINV-3 infections to S. invicta colonies. Correspondingly, viral infection was shown to be detrimental to colony health and productivity. By day 32, all ant colonies exposed to a single 24h pulse treatment of SINV-3 became infected with the virus regardless of the bait formulation. However, the SINV-3 sugar and cricket bait-treated colonies became infected more rapidly than the oil-treated colonies. Sugar and cricket-treated colonies exhibited significant declines in their brood ratings compared with the untreated control and oil bait-treated colonies. Measures of colony health and productivity evaluated at the end of the study (day 47) showed a number of differences among the bait treatments and the control group. Statistically significant and similar patterns were exhibited among treatments for the quantity of live workers (lower), live brood (lower), total colony weight (lower), worker mortality (higher), proportion larvae (lower), and queen weight (lower). Significant changes were also observed in the number of eggs laid by queens (lower) and the corresponding ovary rating in SINV-3-treated colonies. The study provides the first successful demonstration of SINV-3 as a potential biopesticide against fire ants.


MR imaging of thoracic veins.
The thoracic venous system can be visualized and characterized well with MR imaging. In this article, MR sequences that are suited for this purpose (including the more advanced techniques) are reviewed. The normal thoracic venous anatomy and a brief summary of its embryogenesis is provided. The appearances of congenital and acquired abnormalities of the systemic and pulmonary thoracic veins are described. This article also discusses recent applications of MR imaging in the evaluation of the pulmonary veins and the left atrium in patients who have atrial fibrillation.


A comparison of the release of substance P and some synthetic analogues from micropipettes by microiontophoresis or pressure.
The release of substance P (SP) and two analogues by iontophoresis or pressure from microelectrodes was compared. Substance P was released linearly by iontophoresis from electrodes while no release of the analogues was detected. [N-methylphenylalanine8, N-methylglycine9-] SP5-11 (DiMeC7) and [methyl-2-aminoethyl]11 SP (SP-DAE) were released from electrodes by pressure ejection with linear relationships in all cases between pressure and the amounts released. Under the tested experimental conditions, release of substance P by iontophoresis was between 2 and 3 orders of magnitude less than that by pressure over a given time. The release of substance P and the uncharged analogue DiMeC7 by pressure was very similar while release of SP-DAE was one order of magnitude less.


Community-associated meticillin-resistant Staphylococcus aureus carriage in hospitalized patients in tropical northern Australia.
Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) was first reported in remote Australian Aboriginal communities. It is a prominent clinical pathogen in northern Australia with potential for transmission within the local hospital setting. To determine epidemiological characteristics of S. aureus carriage within the Royal Darwin Hospital. We screened two patient groups: an 'admission group' recruited within 48 h of admission; and an 'inpatient group' recruited five or more days after admission. S. aureus isolates were characterized by antibiotic susceptibility testing and genotyped by a multi-locus sequence type-based high-resolution melting scheme. S. aureus carriage on admission was 30.7% of 225 compared with 34.8% among 201 inpatients, with MRSA carriage of 2.2% and 18.9% respectively. We isolated CA-MRSA from 0.9% and 10.4%, and healthcare-associated (HCA)-MRSA from 1.3% and 9.0% of the admission and inpatient groups, respectively. Among the inpatient group, hospital-associated ST239 was the most common MRSA strain. CA-MRSA was represented by one clonal complex (CC) in the admission group (CC5) and seven CCs in the inpatient group (CC1, 93, 5, 6, 30, 75, 88). Inpatient carriage of multiple CA-MRSA lineages suggests selection for and transmission within the hospital of not only typical HCA-MRSA, but also diverse CA-MRSA strains.


Young Children's Attention to What's Going On: Cultural Differences.
This chapter examines children' attention to surrounding events in which they are not directly involved, a way of learning that fits with the cultural approach of Learning by Observing and Pitching In. Research in instructional settings has found that attention to surrounding events is more common among Indigenous Guatemalan Mayan and some US Mexican-heritage children than among middle-class children from several ethnic backgrounds. We examine this phenomenon in a quasi-naturalistic setting to see if the cultural variation in young children's attention to surrounding events in which they were not directly involved extends beyond instructional settings. During a home visit focused on their younger sibling, 19 Guatemalan Mayan and 18 middle-class European American 3- to 5-year olds were nearby but not addressed, as their mother helped their toddler sibling operate novel objects. The Guatemalan Mayan children more frequently attended to this nearby interaction and other third-party activities, whereas the middle-class European American children more often attended to their own activities in which they were directly involved or they fussed or showed off. The results support the idea that in some Indigenous communities of the Americas where young children are included in a broad range of family and community endeavors, children may be especially inclined to attend to ongoing events, even if they are not directly involved or addressed, compared to European American children whose families have extensive experience in Western school ways.


How anchoring proteins shape pain.
Cellular responsiveness to external stimuli can be altered by extracellular mediators which activate membrane receptors, in turn signalling to the intracellular space via calcium, cyclic nucleotides, membrane lipids or enzyme activity. These signalling events trigger a cascade leading to an effector which can be a channel, an enzyme or a transcription factor. The effectiveness of these intracellular events is enhanced when they are maintained in close proximity by anchoring proteins, which assemble complexes of signalling molecules such as kinases together with their targets, and in this way enhance both the speed and the precision of intracellular signalling. The A kinase anchoring protein (AKAP) family are adaptor proteins originally named for their ability to associate Protein Kinase A and its targets, but several other enzymes bound by AKAPs have now been found and a wide variety of target structures has been described. This review provides an overview of anchoring proteins involved in pain signalling. The key anchoring proteins and their ion channel targets in primary sensory neurons responding to painful stimuli (nociceptors) are discussed.


A new 5-bromoindolehydrazone anchored diiodosalicylaldehyde derivative as efficient fluoro and chromophore for selective and sensitive detection of tryptamine and F- ions: Applications in live cell imaging.
A novel indole hydrazone tagged moiety, 2-((5-bromo-1H-indol-2-yl) methylene) hydrazono) methyl)-4, 6-diiodophenol (BHDL) has been developed for the selective and sensitive detection of biogenic tryptamine and F- ions. The binding dexterity of probe BHDL towards F-/tryptamine (TryptA) has been investigated by UV-visible/fluorescence spectroscopy. In the presence of TryptA, probe exhibits strong enhancement in the emission band at 433 nm and the band at 555 nm underwent a blue shift accompanied by a decrease in intensity by the inhibition of Excited State Intramolecular Proton Transfer (ESIPT) on BHDL. Excitingly, complexation with F- ions as well triggers an enhancement in a fluorescence band at 430 nm with the concomitant disappearance of the emission band at 555 nm due to the inhibition of ESIPT and deprotonation process initiated by the hydrogen bonding complex formation. Further, Density Functional Theoretical (DFT) calculations have been performed to support the mechanism functioned on the probe BHDL in the presence of TryptA/F-.


Cognitive impairments in adult mice with RIP140 overexpression in neural stem cells.
Receptor-interacting protein 140 (RIP140) is a transcription co-regulator of several transcription factors and a signal transduction regulator. RIP140 was recently implicated in the regulation of cognitive functions. The gene that encodes RIP140 is located on chromosome 21. An increase in RIP140 expression was observed in the fetal cerebral cortex and hippocampus in Down syndrome patients who exhibited strong cognitive disabilities. We hypothesized that RIP140 overexpression affects cognitive function in adult neural development. The present study used a Cre-dependent adeno-associated virus to selectively overexpress RIP140 in neural stem cells using nestin-Cre mice. RIP140 overexpression efficiency was evaluated at the subgranular zone (SGZ) of the dorsal dentate gyrus (dDG) and the subventricular zone (SVZ) of the lateral ventricles (LVs). Mice with RIP140 overexpression in the SGZ exhibited deficits in cognitive function and spatial learning and memory, measured in the Morris water maze, object-place recognition test, and novel object recognition test. However, overexpression of RIP140 in SVZ only impaired performance in the Morris water maze and novel object recognition test but not in the object-place recognition test. Altogether, these results indicated defects in cognitive functions that were associated with RIP140 overexpression in neural stem cells and revealed a behavioral phenotype that may be used as a framework for further investigating the neuropathogenesis of Down syndrome.


Survey data on gender in relation to youth political discussion and involvement at a Public University in Ghana.
This article presents extensive description of survey data on the political participation of 913 male and female undergraduate students at the University of Ghana. Multi-stage and other sampling procedures were employed to collect the data that took place between 2016 and 2017. Data were analysed using frequencies, percentages and cross-tabulations for each gender separately. The findings revealed that females reported discussing politics more frequently with others than their male counterparts, in addition, ethnicity significantly associated with political discussion and religion significantly associated with political involvement for females. However, males expressed interest and involvement in political activities at both national and student levels more frequently than their female counterparts. The findings support much of the observations in the political behavior literature. Despite the gender imbalance, respondents were partial to engagement in student politics than national politics. It is, therefore, advisable that political parties focus their recruitment efforts on university campuses.


Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses.
Here we have studied the involvement of endothelial heparan sulfate in inflammation by inactivating the enzyme N-acetyl glucosamine N-deacetylase-N-sulfotransferase-1 in endothelial cells and leukocytes, which is required for the addition of sulfate to the heparin sulfate chains. Mutant mice developed normally but showed impaired neutrophil infiltration in various inflammation models. These effects were due to changes in heparan sulfate specifically in endothelial cells. Decreased neutrophil infiltration was partially due to altered rolling velocity correlated with weaker binding of L-selectin to endothelial cells. Chemokine transcytosis across endothelial cells and presentation on the cell surface were also reduced, resulting in decreased neutrophil firm adhesion and migration. Thus, endothelial heparan sulfate has three functions in inflammation: by acting as a ligand for L-selectin during neutrophil rolling; in chemokine transcytosis; and by binding and presenting chemokines at the lumenal surface of the endothelium.


The cellular slime mold guild and its bacterial prey: growth rate variation at the inter- and intraspecific levels.
A guild of cellular slime molds (CSM) consisting of two isolates from each of five species, representing two genera, and obtained from the same square meter of forest soil exhibited extensive growth rate variation when tested on a suite of 18 bacteria isolated from the same soil. Significant growth rate differences were found at each taxonomic level examined: among species of different genera, between genera, among species within genera, and between isolates (=clones) within species. The type of bacteria used as prey determined the relative rank of the growth rates in different CSM isolates, as well as the taxonomic level at which significant differences were found. We suggest a possible reconciliation between a previous hypothesis, based on competition, and contradictory experimental work on resource partitioning in this guild of bacterial predators. Our results raise a question about the efficacy of using single genotypes to represent a species when ecological ideas are developed through laboratory investigations.


Yarning about pain: Evaluating communication training for health professionals at persistent pain services in Queensland, Australia.
Providing cultural education to health professionals is essential in improving the quality of care and outcomes for Aboriginal and Torres Strait Islander patients. This study reports the evaluation of a novel training workshop used as an intervention to improve communication with Aboriginal and Torres Strait Islander patients of persistent pain services. In this single-arm intervention study, health professionals undertook a one-day workshop, which included cultural capability and communication skills training based on a clinical yarning framework. The workshop was delivered across three adult persistent pain clinics in Queensland. At the end of the training, participants completed a retrospective pre/post evaluation questionnaire (5 points Likert scale, 1 = very low to 5 = very high), to rate their perceived importance of communication training, their knowledge, ability and confidence to communicate effectively. Participants also rated their satisfaction with the training and suggested improvements for future trainings. Fifty-seven health professionals were trained (N = 57/111; 51% participation rate), 51 completed an evaluation questionnaire (n = 51/57; 90% response rate). Significant improvements in the perceived importance of communication training, knowledge, ability and confidence to effectively communicate with Aboriginal and Torres Strait Islander patients were identified (p < 0.001). The greatest increase was in the perceived confidence pre-training mean of 2.96 (SE = 0.11) to the post-training mean of 4.02 (SE = 0.09). This patient-centred communication training, delivered through a novel model that combines cultural capability and the clinical yarning framework applied to the pain management setting, was highly acceptable and significantly improved participants' perceived competence. This method is transferrable to other health system sectors seeking to train their clinical workforce with culturally sensitive communication skills.


A computerized audit of 15,009 emergency department records.
The text of 15,009 emergency department medical records was reviewed with the use of a computer program that detected the presence or absence of key words and phrases. The search focused on "trigger diagnoses," that is, any diagnoses associated with an above-average risk for an undetected but more serious condition. Included were the trigger diagnoses from the five high-risk areas of extremity laceration, epiglottitis, abdominal pain, meningitis, and myocardial infarction. The three kinds of medical records that were compared were handwritten records, records dictated and transcribed, and records created by a voice-activated word processor. From a risk management perspective, inclusion of critical pertinent positives and negatives was taken as an index of quality from a risk management perspective, and records created by a voice-activated word processor using real-time risk management prompts were superior to handwritten and dictated records. The computer holds promise as a vehicle to reduce the cost and frequency of malpractice risk in the ED and as a teaching tool to improve the quality of care.


Editorial.
Many people who are relative newcomers to the field of healthcare research are often wary about seeking to have their findings published in a journal. Ask them why, and they are likely to tell you that the articles they read in peer-reviewed journals bear little relationship to their own, flawed studies.


Daily geographies of caregivers: mobility, routine, scale.
The bulk of care provided to elderly people living in the community and needing assistance is provided informally by family and friends. This paper investigates themes from an interpretation of interviews with informal caregivers about their experiences of caring for a frail, ill, or disabled elderly person at home. These themes include mobility, routine, and inter-relationships of scale. The caregivers' narratives illustrate the interconnected nature of physical, material and social, emotional aspects of care, and the profound spatial and social impact of providing informal care to a family member on their everyday lives. These are often at odds with political and social constructions of what it means to care at home. Concepts of space, place, and time are shown to be a helpful framework through which to understand issues and experiences of caring. The social and the physical aspects of the many interconnected scales and places which caregivers negotiate on an everyday basis both shape and are shaped by caregiving.


Alcohol use and alcohol-related consequences based on gender and sexual orientation among college students.
Research has not yet investigated how the association between alcohol and alcohol-related consequences differs across cisgender heterosexual women (CHW), cisgender heterosexual men (CHM), and sexual and gender minority (SGM) college students. Participants were N = 754 college students (34.5% CHW [n = 260]; 34.5% CHM [n = 260]; 31.0% SGM [n = 234]) between the ages 18 and 25 who completed a survey on sexual orientation, gender identity, alcohol use (i.e., average drinks per week), and alcohol-related consequences. Among individuals who reported alcohol use, CHM reported significantly more drinks per week compared to CHW and SGM. The logistic model of a zero-inflated negative binomial regression indicated that excess zeros in the alcohol-related consequences were more likely among (1) nondrinkers and (2) SGM compared to CHM. The count portion of the model indicated that, among drinkers, there was a positive association between drinks per week and alcohol-related consequences. Estimated alcohol-related consequences per drink were 1.90% higher among CHW than CHM and 2.76% higher among SGM than CHM. Exploratory analyses did not find significant differences in outcomes between cisgender female and male sexual minority students. Findings suggest that although CHW and SGM students consume less alcohol than CHM, these students experience more alcohol-related consequences per drink. This study advances the field's knowledge of alcohol use patterns and consequences among SGM college students. There is a need for alcohol education programming that is tailored to the unique experiences, identities, and minority stressors of SGM college students.


Predictive value of the kinetics of procalcitonin and C-reactive protein for early clinical stability in patients with bloodstream infections due to Gram-negative bacteria.
To investigate whether the magnitude of the change in procalcitonin (PCT) and C-reactive protein (CRP) levels between day 1 and day 2 after the blood culture date is associated with early clinical stability (ECS) on day 3 in patients with bacteremia due to Gram-negative bacteria (GNB). A prospective cohort study carried out in a 950-bed tertiary hospital in Spain between March 2013 and May 2014. Patients with GNB bacteremia were included. Changes in PCT and CRP kinetics from day 1 to day 2 (∆%PCT, ∆%CRP) were expressed as percentage of decline in blood levels. Logistic regression was used to identify predictors of ECS. Classification and regression tree analysis was performed to identify breakpoints. The discriminatory power of ∆%CRP and ∆%PCT as predictors of ECS was assessed by the area under the ROC (AUROC). 71 patients were included, and 53 (74.56%) reached ECS. Multivariate analyses showed that SOFA score on day 1, ∆%PCT, and ∆%CRP were associated with ECS after controlling for confounders. ∆%PCT ≥ 30% (decline) and ∆%CRP ≥ 10% (decline) predicted ECS only among patients with SOFA≤3 on day 1 (n = 54; 43 reached ECS). In these patients, the AUROCs for the prediction of ECS were 0.96 (95% CI: 0.90-1) for ∆%CRP and 0.96 (95% CI: 0.90-1) for ∆%PCT, respectively. In the subgroup of patients with a SOFA score on day 1 ≤3, a ≥30% decline in PCT or a ≥10% decline in CRP between day 1 and day 2 was a very good predictor of ECS (which in turn was associated with a lower 30-day mortality and a greater clinical cure on day 14). Patients who do not achieve this decrease may need more intensive workup. In this subgroup (with a SOFA on day 1 ≤3), CRP may be preferred due to its lower cost.


Ultrasonic frogs show hyperacute phonotaxis to female courtship calls.
Sound communication plays a vital role in frog reproduction, in which vocal advertisement is generally the domain of males. Females are typically silent, but in a few anuran species they can produce a feeble reciprocal call or rapping sounds during courtship. Males of concave-eared torrent frogs (Odorrana tormota) have demonstrated ultrasonic communication capacity. Although females of O. tormota have an unusually well-developed vocal production system, it is unclear whether or not they produce calls or are only passive partners in a communication system dominated by males. Here we show that before ovulation, gravid females of O. tormota emit calls that are distinct from males' advertisement calls, having higher fundamental frequencies and harmonics and shorter call duration. In the field and in a quiet, darkened indoor arena, these female calls evoke vocalizations and extraordinarily precise positive phonotaxis (a localization error of <1 degrees ), rivalling that of vertebrates with the highest localization acuity (barn owls, dolphins, elephants and humans). The localization accuracy of O. tormota is remarkable in light of their small head size (interaural distance of <1 cm), and suggests an additional selective advantage of high-frequency hearing beyond the ability to avoid masking by low-frequency background noise.


Dual roles of hyaluronic acids in multilayer films capturing nanocarriers for drug-eluting coatings.
We developed hyaluronic acid (HA)-based multilayer films capturing polymeric nanocarriers (NCs) for drug delivery. The electrostatic interactions between positively charged linear polyethylene imines (LPEI) and negatively charged HAs are the main driving forces to form multilayers based on the layer-by-layer (LbL) deposition. NCs were easily incorporated within the multilayer film due to intra- and/or inter-hydrogen bonding among HA chains. The amount of NCs captured by the HA chains was varied by the ratio between HAs and NCs as well as the length (i.e., molecular weight) and absolute number density of HAs in solution. Biocompatibility of the NC-capturing HA multilayer films was tested with the human dermal fibroblast (HDF) culture. In addition, the controlled release of paclitaxel (PTX) from the HA multilayer films successfully led to the apoptosis of human aortic smooth muscle cells (hSMC) in vitro, implying that the NC-capturing HA multilayer films would be quite useful as drug-eluting stent systems to prevent the restenosis after surgery.


Expression of a variant form of actin and additional polypeptide changes following chemical-induced in vitro neoplastic transformation of human fibroblasts.
Malignant human fibroblasts, transformed in vitro by a single chemical treatment, and the untransformed parental cells have been compared by two-dimensional gel electrophoresis of their proteins. One transformed cell line, HUT-14, exhibits an abundance of a new polypeptide, A' (pI 5.2; molecular weight 44,000), amounting to approximately 3% of the cellular protein. There are at least 23 additional differences in polypeptides out of greater than 1000 electrophoretically distinguishable species. The A' polypeptide has been identified as a variant form of actin by immunoprecipitation with anti-actin antibody and comparison of its tryptic peptide patterns with those produced by beta- and gamma-actin polypeptides also found in HUT-14 cells. A' is distinguishable from the normal forms of actin (alpha, beta, and gamma polypeptides) in that it is more acidic and migrates at a slower rate in sodium dodecyl sulfate gels. Synthesis of A' may occur as a result of a somatic mutation affecting one of the normal actin genes. The electrophoretic behavior of A' in two-dimensional gels is compatible with several mutation models.


Differences in cancer incidence and mortality among socio-economic groups.
In this article studies on the association between socioeconomic status (SES) and risk for cancer at different sites are reviewed. The review is restricted to studies conducted in affluent societies, after 1970. Only studies using income, education and/or occupation as SES indicators are included. A more or less consistent positive association between SES and cancer risk was found for colon and breast cancer. More or less consistent inverse associations were found for lung, stomach, oropharyngeal and esophageal cancer. Inconsistent associations were reported for cancer of the rectum and pancreas. Possible explanations for SES differences in cancer risk are discussed with special emphasis on lifestyle variables related to cancer risk. It is concluded that it is still unclear whether the reported associations can be (partially) attributed to lifestyle related risk factors for cancer such as smoking, nutritional habits, drinking habits and reproductive factors.


A new glycoside, 3-O-demethylcolchicine-3-O-alpha-d-glucopyranoside, from Gloriosa superba seeds.
A new colchicine glycoside, 3-O-demethylcolchicine-3-O-alpha-D-glucopyranoside, has been isolated from Gloriosa superba seeds. The assigned structure has been corroborated by spectroscopic data and enzymatic hydrolysis.


Community-acquired and hospital-acquired bacterial co-infections in patients hospitalized with Covid-19 or influenza: a retrospective cohort study.
Bacterial co-infections are believed to be less frequent in patients with Covid-19 than influenza, but frequencies varied between studies. This single-center retrospective, propensity score-matched analysis included adult patients with Covid-19 or influenza admitted to normal-care wards between 02/2014 and 12/2021. Covid-19 cases were propensity score matched to influenza cases at a 2:1 ratio. Community-acquired and hospital-acquired bacterial co-infections were defined as positive blood or respiratory cultures ≤ 48 h or > 48 h after hospital admission, respectively. The primary outcome was comparison of community-acquired and hospital-acquired bacterial infections between patients with Covid-19 and influenza in the propensity score-matched cohort. Secondary outcomes included frequency of early and late microbiological testing. A total of 1337 patients were included in the overall analysis, of which 360 patients with Covid-19 were matched to 180 patients with influenza. Early (≤ 48 h) microbiological sampling was performed in 138 (38.3%) patients with Covid-19 and 75 (41.7%) patients with influenza. Community-acquired bacterial co-infections were found in 14 (3.9%) of 360 patients with Covid-19 and 7 (3.9%) of 180 patients with influenza (OR 1.0, 95% CI 0.3-2.7). Late (> 48 h) microbiological sampling was performed in 129 (35.8%) patients with Covid-19 and 74 (41.1%) patients with influenza. Hospital-acquired bacterial co-infections were found in 40 (11.1%) of 360 patients with Covid-19 and 20 (11.1%) of 180 patients with influenza (OR 1.0, 95% CI 0.5-1.8). The rate of community-acquired and hospital-acquired bacterial co-infections was similar in hospitalized Covid-19 and influenza patients. These findings contrast previous literature reporting that bacterial co-infections are less common in Covid-19 than influenza.


Characterization of a multifunctional PEG-based gene delivery system containing nuclear localization signals and endosomal escape peptides.
Endosomal escape and nuclear localization are two barriers to gene delivery that need to be addressed in the design of new nonviral gene delivery vehicles. We have previously synthesized low-toxicity polyethylene glycol (PEG)-based vehicles with endosomal escape functionalities, but it was determined that the transfection efficiency of PEG-based vehicles that escaped the endosome was still limited by poor nuclear localization. Two different nuclear localization signal (NLS) peptides, SV40 and TAT, were coupled to PEG-based vehicles with DNA-binding peptides (DBPs) to determine the effect of NLS peptides on the transfection efficiency of PEG-based gene delivery vehicles. Coupling one SV40 peptide, a classical NLS, or two TAT peptides, a nonclassical NLS, to PEG-DBP vehicles increased the transfection efficiency of PEG-DBP/DNA particles 15-fold and resulted in similar efficiency to that of a common cationic polymer vehicle, polyethylenimine (PEI). The transfection efficiency of both types of PEG-DBP-NLS particles was further increased 7-fold in the presence of chloroquine, suggesting that the transfection efficiency of PEG-DBP-NLS particles is limited by their ability to escape the endosome. To develop particles that could escape the endosome and target the nucleus, a mixture of PEG-DBP-NLS vehicles and PEG-based vehicles with DBPs and endosomal escape peptides were complexed with plasmid DNA to form multifunctional particles that had a transfection efficiency 2-3 times higher than that of PEI. Additionally, the PEG-based vehicles were less toxic and more resistant to nonspecific protein adsorption than PEI, making them an attractive alternative for nonviral gene delivery.


Biochemical responses of rat and mouse lung to inhaled nickel compounds.
Nickel subsulfide (Ni3S2), nickel sulfate (NiSO4), and nickel oxide (NiO) are encountered occupationally in the nickel refining and electroplating industries, with inhalation being a common route of exposure. The purposes of this study were to evaluate the biochemical responses of lungs of rats and mice exposed for 13 weeks to occupationally relevant aerosol concentrations of Ni3S2, NiSO4, and NiO, to correlate biochemical responses with histopathologic changes, and to rank the compounds by toxicity. Biochemical responses were measured in bronchoalveolar lavage fluid (BALF) recovered from lungs of exposed animals. Parameters evaluated in BALF were lactate dehydrogenase (LDH), beta-glucuronidase (BG), and total protein (TP). Total and differential cell counts were performed on cells recovered in BALF. All compounds produced an increase in LDH, BG, TP, and total nucleated cells, and an influx of neutrophils, indicating the presence of a cytotoxic and inflammatory response in the lungs of exposed rats and mice. Increases in BG were greater than increases in LDH and TP for both rats and mice. Chronic active inflammation, macrophage hyperplasia, and interstitial phagocytic cell infiltrates were observed histologically in rats and mice exposed to all compounds. Statistically significant increases in BG, TP, neutrophils, and macrophages correlated well with the degree of chronic active inflammation. Results indicated a toxicity ranking of NiSO4 greater than Ni3S2 greater than NiO, based on toxicities of the compounds at equivalent mg Ni/m3 exposure concentrations.


Construction of an infectious full-length and eGFP-tagged cDNA clone of a chilli ringspot virus isolate from Yunnan province, China.
Chilli ringspot virus (ChiRSV; genus Potyvirus) was one of several viruses previously detected in pepper samples with severe yellowing and curling symptoms growing in Wenshan, Yunan province, China. We now report the full-length sequence of ChiRSV-YN/Wenshan (MZ269480), which has 88.5-98.9% nucleotide sequence identity to other published ChiRSV isolates. A full-length cDNA infectious clone was constructed. This cDNA and an eGFP-tagged clone were infectious, leading to systemic symptoms in both Nicotiana benthamiana and Capsicum spp. Recombinant clones containing the P1 protein coding region of other ChiRSV isolates differed in their pathogenicity. Single infection by ChiRSV caused mild mosaic or leaf crinkling in Capsicum frutescens L. and Capsicum annuum L.


The distribution and regulation of aromatase activity in the central nervous system.
Our data demonstrate that androgen-dependent AA is found in areas of the brain that are essential for the neuroendocrine control of gonadotropin secretion and sexual behavior. However, until we know more about the neurons that contain AA, e.g., whether they are peptidergic or catecholaminergic, we can not speculate about the neuronal functions that depend on local estrogen formation. In fact, the association of AA with neurons and not glia has only recently been demonstrated. That estrogens and androgens synergize in the regulation of various neuroendocrine functions has been known for many years, but an explanation of the synergism at the cellular level was not available. One explanation for this synergism may lie in our recent observation that the administration of exogenous estradiol to castrated rats increases androgen-receptor concentrations in specific brain nuclei. Perhaps locally formed estrogens work in a similar fashion to regulate androgen receptors in the brain of the intact male.


Testosterone, LH and FSH in patients with treated testicular carcinomas.
Patients with testicular cancer were treated by semicastratio and in some cases by retroperitoneal surgery. The diminution of testicular parenchyma to about 50% results to a low serum level of testosterone, but elevated serum level of LH and FSH. 3 years after surgery and irradiation this is not a pathological finding but appears to be a typical pattern. As it is difficult to differentiate embryonal carcinomas and choriocarcinomas from pure embryonal carcinomas an estimation of serum level of LH and FSH may be of use by the diagnosis.


A Golgi study of rat neostriatal neurons: light microscopic analysis.
At least two types of large neurons (somatic cross-sectional areas, SA greater than 300 microns2) and five-types of medium neurons (SA between 100 and 300 microns2) were distinguished in Golgi preparations of the adult rat neostriatum. Type I large cells had aspinous somata with long, radiating, sparsely spined dendrites which were sometimes varicose distally, whereas type II large cells had spines on both somatic and dendritic surfaces. Type I medium cells had aspinous somata and proximal dendrites, but their distal dendrites were densely covered with spines. Type II medium cells had somatic spines, and their radiating dendrites were sparsely spined. Other medium cells had no somatic spines: Type III cells had poorly branched and sparsely spined dendrites. Type IV cells had profusely branched, sparsely spined dendrites. Type V cells had radiating and varicose dendrites which could also be sparsely spined. Several small neurons (SA mostly less than 100 microns2) were also found in the rat neostriatum: Some had aspinous soma with sparsely spined dendrites; others had somatic spines. Except for the type II large cells, intrinsic axon collaterals were observed for every type of neuron, indicating that they all had local integrating functions.


[Targeted therapy of urological tumours. Experimental field or established therapeutic approach?].
Unlike conventional systemic chemotherapies, the aim of targeted therapeutic approaches is not to address general mechanisms involved in cellular replication. In contrast, they aim at such regulatory pathways that have been identified to be involved in the progression of human malignant disease. Whereas the application of targeted therapeutic modalities is well established for the treatment of metastatic renal cell cancer, only very few data on their clinical efficacy during the treatment of other urological tumours such as prostate and bladder cancer are currently available. The aim of this paper is to reflect on the current status regarding the relevance of targeted therapeutic approaches during the treatment of urological cancers of different origin.


Real-World Study of Regional Differences in Patient Demographics, Clinical Characteristics, and BRCA1/2 Mutation Testing in Patients with Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer in the United States, Europe, and Israel.
Genetic mutations in breast cancer susceptibility gene 1 or 2 (BRCA1/2) confer a high risk for developing breast cancer; however, at least 50% of women with BRCA1/2 mutations go undiagnosed. This study evaluated differences in patient demographics, clinical characteristics, and BRCA1/2 mutation testing in the USA, European Union (EU4), and Israel in a real-world population of patients with human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). This study was a retrospective analysis of data from the Adelphi Real World ABC Disease Specific Programme in the USA, EU4, and Israel. Medical oncologists completed a patient record form, which included detailed questions on demographics, clinical assessments and outcomes, and treatment history. Eligible patients were at least 18 years of age and receiving therapy for stage IIIb-IV ABC. Among the 2527 study patients, 407 were from the USA, 1926 were from the EU4, and 194 were from Israel; 86% had hormone receptor-positive (HR+)/HER2- ABC and 14% had triple-negative breast cancer (TNBC). Israeli patients had a higher rate of family history of BRCA-related cancer (69%) compared with patients in the EU4 (18%; p < 0.0001) and USA (18%; p < 0.0001). Among patients with HR+/HER2- ABC, the BRCA1/2 testing rate was 99% in Israel, 37% in the EU4, and 68% in the USA (p < 0.0001 vs Israel and the EU4). The age of tested patients was significantly younger in Israel (56 years) compared with the EU4 (59 years; p = 0.016 vs Israel) and USA (64 years; p < 0.0001 vs Israel and the EU4). Among patients with TNBC, the BRCA1/2 testing rate was 100% in Israel, 78% in the EU4 (p < 0.0001 vs Israel), and 93% in the USA (p < 0.002 vs the EU4). Among tested patients, genetic counseling rates were also higher in Israel (98%) compared with the EU4 (40%; p < 0.0001) and USA (38%; p < 0.0001). Testing and genetic counseling rates for BRCA1/2 mutations were very high in Israel, potentially due to the high rate of family history of BRCA-related cancer in this population and higher general awareness of genetic testing. In the EU4 and USA, overall rates of testing for BRCA1/2 mutations and genetic counseling were significantly lower compared with Israel. Given the high risk of breast cancer in BRCA1/2 mutation carriers and the efficacy of new therapies in treating ABC with a BRCA1/2 mutation, efforts should be made to improve BRCA1/2 testing rates in Europe and the USA.


Involvement of carbonyl reductase in superoxide formation through redox cycling of adrenochrome and 9,10-phenanthrenequinone in pig heart.
The effects of adrenochrome, a metabolite of epinephrine (adrenaline), and 9,10-phenanthrenequinone (PQ), a component of diesel exhaust particles, on the stereoselective reduction of 4-benzoylpyridine (4-BP) were examined in pig heart cytosol. PQ was a potent inhibitor for the 4-BP reduction, while adrenochrome was a poor inhibitor. A similar result was observed in the effects of adrenochrome and PQ on the reduction of all-trans retinal. Furthermore, although PQ mediated efficiently the formation of superoxide anion radical through its redox cycling in pig heart cytosol, adrenochrome had no ability to mediate the superoxide formation. These may be because the reactivity for adrenochrome, catalyzed by pig heart carbonyl reductase (PHCR), is much lower than that for PQ. The optimal pH for the reduction of PQ in pig heart cytosol was around 5.5. Dicumarol, a potent inhibitor of DT-diaphorase, had little effect on the time course of NADPH oxidation during the reduction of PQ. Therefore, it is concluded that PHCR plays a critical role in superoxide formation through redox cycling of PQ.


Spontaneous intracranial hypotension: updates from diagnosis to treatment.
Spontaneous intracranial hypotension (SIH) is caused by spinal cerebrospinal fluid (CSF) leaks, which result in continued loss of CSF volume and multiple debilitating clinical manifestations. The estimated annual incidence of SIH is 5/100,000. Diagnostic methods have evolved in recent years due to improved understanding of pathophysiology and implementation of advanced myelographic techniques. Here, we synthesize recent updates and contextualize them in an algorithm for diagnosis and treatment of SIH, highlighting basic principles and points of practice variability or continued debate. This discussion includes finer points of SIH diagnosis, CSF leak classification systems, less common types and variants of CSF leaks, brain MRI Bern scoring, potential SIH complications, key technical considerations, and positioning strategies for different types of dynamic myelography. The roles of conservative measures, non-targeted or targeted blood patches, surgery, and recently developed endovascular techniques are presented.


Is serum creatinine a reliable expression of an adequate cyclosporine immunosuppression?
In 13 renal transplant patients with an excellent graft function, but concomitant abnormal T6 CsA plasma levels (CsA plasma level, 6 hours after oral administration of the drug), dose adjustments of CsA were performed until a normal T6 was achieved. A significant decrease of serum creatinine values was obtained after dose modification. Prophylactic monitoring of CsA immunosuppression by T6 could be a means of avoiding nephrotoxicity or undertreatment in patients with acceptable serum creatinine levels and unsuspected drug related renal dysfunction.


Coincidence planar imaging for dynamic [18F]FDG uptake in nude mice with tumors and inflammation: correlated with histopathology and micro-autoradiography.
The Institute of Nuclear Energy Research of Taiwan has developed a dynamic coincidence detection device for positron emitted radiotracer pharmacodynamic study in small mice models. In this study, we set up an experimental paradigm by determining [fluorine-18]-2-deoxy-2-fluoro-D-glucose ([18F]FDG) dynamic uptake in tumors and inflammations in nude mice as the foundation for future applications in therapy development. Histopathology and micro-autoradiography of these tumors and inflammations were obtained for confirmation. Dynamic coincidence planar images of six tumors and two inflammations in nude mice were acquired over 4 hours immediately after injection of 25.9 MBq of [18F]FDG into the right thigh of each animal. After image reconstruction, the lesion-to-background ratios were calculated in regions of interest over the lesion and contralateral thigh to determine the equilibrium status of the radiotracer. All mice were sacrificed for histopathologic examination and six of the mice were examined with micro-autoradiography. [18F]FDG uptake in tumors and inflammations both reached equilibrium about 3 hours after injection. At equilibrium, [18F]FDG uptake into tumors was two to four times higher than the background. Uptake into the 4-day and 8-day inflammations was 2.3 and 5.5 times higher than the background, respectively. Histopathology showed macrophage and neutrophil infiltration around the tumors and in the inflammations. Micro-autoradiography showed dense silver grains in the granulation tissue surrounding the tumors and inflammations. The preliminary results suggested that dynamic [18F]FDG coincidence planar imaging can help in determining the suitable time for static [18F]FDG imaging in nude mice models. The optimal time for static [18F]FDG positron emission tomography imaging was around 3 hours after injection. The paradigm for determining a dynamic [18F]FDG uptake pattern was demonstrated for future new therapeutic drug experimental use.


Strong controls of daily minimum temperature on the autumn photosynthetic phenology of subtropical vegetation in China.
Vegetation phenology research has largely focused on temperate deciduous forests, thus limiting our understanding of the response of evergreen vegetation to climate change in tropical and subtropical regions. Using satellite solar-induced chlorophyll fluorescence (SIF) and MODIS enhanced vegetation index (EVI) data, we applied two methods to evaluate temporal and spatial patterns of the end of the growing season (EGS) in subtropical vegetation in China, and analyze the dependence of EGS on preseason maximum and minimum temperatures as well as cumulative precipitation. Our results indicated that the averaged EGS derived from the SIF and EVI based on the two methods (dynamic threshold method and derivative method) was later than that derived from gross primary productivity (GPP) based on the eddy covariance technique, and the time-lag for EGSsif and EGSevi was approximately 2 weeks and 4 weeks, respectively. We found that EGS was positively correlated with preseason minimum temperature and cumulative precipitation (accounting for more than 73% and 62% of the study areas, respectively), but negatively correlated with preseason maximum temperature (accounting for more than 59% of the study areas). In addition, EGS was more sensitive to the changes in the preseason minimum temperature than to other climatic factors, and an increase in the preseason minimum temperature significantly delayed the EGS in evergreen forests, shrub and grassland. Our results indicated that the SIF outperformed traditional vegetation indices in capturing the autumn photosynthetic phenology of evergreen forest in the subtropical region of China. We found that minimum temperature plays a significant role in determining autumn photosynthetic phenology in the study region. These findings contribute to improving our understanding of the response of the EGS to climate change in subtropical vegetation of China, and provide a new perspective for accurately evaluating the role played by evergreen vegetation in the regional carbon budget. The online version contains supplementary material available at 10.1186/s40663-021-00309-9.


Use of anti-asthmatic drugs in Italy: analysis of prescriptions in general practice in the light of guidelines for asthma treatment.
Our aim was to analyse anti-asthmatic drug utilisation in primary health care in a Northern Italian region in the light of guidelines for asthma treatment. We collected all prescriptions for anti-asthmatic agents reimbursed in 1998 in six local health authorities (overall population: 1,909,192 inhabitants) of Emilia Romagna (Northern Italy). The asthmatic cohort was defined as the population of subjects aged 20-44 years receiving at least one prescription of an anti-asthmatic agent devoid of indications for transient respiratory diseases. In order to include routine users, the asthmatic cohort was restricted to those subjects with at least one prescription in the first quarter of 1998. Anti-asthmatic agents were classified according to their therapeutic role as follows: maintenance therapy for mild-moderate asthma (Mm); maintenance therapy for severe asthma (Ms); quick relief for mild attack (Qm) and quick relief for severe attack (Qs). The asthmatic cohort included 11,518 subjects; of these, 47% received only one prescription in 1998. The most frequent regimens were Mm+Qm (25%) and Qm alone (23%). Some regimens appeared not to be in accordance with international recommendations. The main reasons were lack of drugs for quick relief (36%), use of long-term beta(2)-adrenoceptor agonists (Ms drugs) without quick-relief or anti-inflammatory agents (10% of the cohort and 56% of the recipients of Ms drugs) and presence of fixed-dose combinations (27%). In 76% of the patients treated with Mm drugs (mainly inhaled steroids), the total amount of drugs prescribed over the 1-year period covered less than 150 days. The use of anti-asthmatic drugs in general practice in Italy does not seem to comply with the international recommendations especially with regard to the use of quick-relief agents. Active interventions to implement guidelines and monitor the choice of drug regimens are warranted.


Everybody's welcome: The big tent approach to epigenetic drug discovery.
The rapid expansion of epigenetics research is fueled by the increasing understanding that epigenetic processes are critical to regulating cellular development and dysfunction of epigenetic programs is responsible for a diverse set of human pathologies, including cancer, autoimmune and neurodegenerative diseases. The expansive set of components contributing to epigenetic disease mechanisms and the often reversible nature of epigenetic lesions provide prime opportunities for the development of novel therapeutic strategies. Here, we provide an overview of epigenetics and its relationship to disease, discuss current epigenetics-based therapies and suggest new avenues for the identification of therapies targeting deregulated epigenetic programs in disease.


Optimal foraging and ontogeny; food selection by Haplochromis piceatus.
We examined the influence of satiation level, prey density and light intensity on food uptake rate through the ontogeny of Haplochromis piceatus. Prey handling in the buccal cavity was found to be the main factor limiting prey uptake rate under light circumstances and at a sufficiently high prey density. Food uptake rate per unit body weight of different sizes of H. piceatus was equal when feeding on Chaoborus but decreased with increasing fish size when feeding on Daphnia magna. In choice experiments with Chaoborus and D. magna, prey selection by H. piceatus of all sizes was according to the predictions based on Charnov's 1976 model.


Paradoxical position of vertebral veins in cancer carriage.
A new era dawned in 1940 when Batson published the theory that the vertebral venous system plays an important role in cancer carriage. He emphasized that this route comes into play with any natural movement such as coughing. Now, cough is a prominent feature of lung cancer. Therefore, this tumor is optimally positioned for utilizing the vertebral venous route of spread. However, when three major distribution patterns of lung cancer are examined critically, expectations from Batson's theory are not confirmed. If this paradox is recognized and explained, the prospects for solving the mysteries of human cancer metastasis will probably improve.


Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility.
Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements.


Cytomegalovirus-related corneal endotheliitis: A review article.
Cytomegalovirus (CMV)-related corneal endotheliitis is an inflammation of the corneal endothelium caused by CMV. It typically presents as coin-shaped keratic precipitates (KPs), with or without corneal edema, in otherwise healthy individuals. It may be associated with anterior uveitis and raised intraocular pressure (IOP). Patients with CMV-related corneal endotheliitis respond to systemic and topical ganciclovir with the use of topical steroid. Making an accurate early diagnosis is crucial in preventing loss of corneal endothelial cells and unnecessary treatment resulting from misdiagnosis in these patients.


Rates of ion movement from plasma to endolymph in the dogfish.
The rates of movement of Na+, Rb+, Cl- and HCO3- from plasma to endolymph were studied in the elasmobranch fish, Squalus acanthias, by use of the appropriate isotopes. Rb+ was used as a marker for K+. The half-times to equilibrium for Na+, Rb+ and Cl- were about 100 hours; for HCO3- it was 6 hours. The equilibrium ratios, endolymph/plasma, are Na+ 0.87, K+ 26, Cl- 1.37, HCO3- 1.47. Carbonic anhydrase inhibition decreased the rate of HCO3- accumulation, suggesting that the process is actually the formation of endolymphatic HCO3- from plasma or tissue CO2. Increase in plasma pCO2 elevates endolymph HCO3- concentration. The secretory tissue contains carbonic anhydrase and Na-K-ATPase. These and other data suggest that a dominant feature of endolymph chemistry may be HCO3- formation linked in some fashion with K+ transport, through rates catalyzed by these two enzymes.


The surface fine structure of the ependymal lining of the lateral ventricle in rats with hereditary hydrocephalus.
The ependyma of the lateral ventricle of rats with hereditary hydrocephalus was studied using scanning electron microscopy. Normal rats from the same litters were used as control animals. The surface morphology of the lateral ventricle of normal rats corresponded to results reported by other authors. The most prominent changes in the surface morphology of the ependyma of the hydrocephalic rats were seen in the cilia. They were shortened, fewer in number and clumped or matted. The surface of the ependymal cells was flattened and contained small, irregular projections. The number of large supraependymal cells, regarded as neurons, appeared to have diminished in the hydrocephalic rats. The number of supraependymal macrophages was greatly increased in these rats, suggesting the existence of an ependymitis.


Single-cell expression profile of Drosophila ovarian follicle stem cells illuminates spatial differentiation in the germarium.
How stem cell populations are organized and regulated within adult tissues is important for understanding cancer origins and for developing cell replacement strategies. Paradigms such as mammalian gut stem cells and Drosophila ovarian follicle stem cells (FSC) are characterized by population asymmetry, in which stem cell division and differentiation are separately regulated processes. These stem cells behave stochastically regarding their contributions to derivative cells and also exhibit dynamic spatial heterogeneity. Drosophila FSCs provide an excellent model for understanding how a community of active stem cells maintained by population asymmetry is regulated. Here, we use single-cell RNA sequencing to profile the gene expression patterns of FSCs and their immediate derivatives to investigate heterogeneity within the stem cell population and changes associated with differentiation. We describe single-cell RNA sequencing studies of a pre-sorted population of cells that include FSCs and the neighboring cell types, escort cells (ECs) and follicle cells (FCs), which they support. Cell-type assignment relies on anterior-posterior (AP) location within the germarium. We clarify the previously determined location of FSCs and use spatially targeted lineage studies as further confirmation. The scRNA profiles among four clusters are consistent with an AP progression from anterior ECs through posterior ECs and then FSCs, to early FCs. The relative proportion of EC and FSC clusters are in good agreement with the prevalence of those cell types in a germarium. Several genes with graded profiles from ECs to FCs are highlighted as candidate effectors of the inverse gradients of the two principal signaling pathways, Wnt and JAK-STAT, that guide FSC differentiation and division. Our data establishes an important resource of scRNA-seq profiles for FSCs and their immediate derivatives that is based on precise spatial location and functionally established stem cell identity, and facilitates future genetic investigation of regulatory interactions guiding FSC behavior.


Laser scanning in vivo confocal microscopy and quantitative aesthesiometry reveal decreased corneal innervation and sensation in keratoconus.
The purpose of this study was to quantitatively analyse laser scanning in vivo confocal microscopy images of the corneal epithelium and sub-basal nerve plexus in patients with keratoconus and to correlate these microstructural observations with corneal sensitivity. A total of 31 eyes of 31 normal human subjects, and 27 eyes of 27 subjects with an established diagnosis of keratoconus were recruited. Twelve subjects with keratoconus had never worn contact lenses (K-NCL). Fifteen subjects with keratoconus wore contact lenses routinely (K-CL). All eyes were examined using slit-lamp biomicroscopy, Orbscan topography, non-contact corneal aesthesiometry, and laser scanning in vivo confocal microscopy. Central corneal sensation was significantly lower in K-CL compared to normal (P=0.028). However, there was no significant difference in corneal sensation between the normal and K-NCL groups (P=0.059). Both sub-basal nerve density (P<0.001) and basal epithelial density (P<0.001) were significantly lower than normal in all keratoconic subjects. Central corneal sensation was only significantly correlated with sub-basal nerve density (P=0.001) and was not significantly correlated with any of the basal epithelial parameters. Sub-basal nerve density showed significant positive correlation with basal epithelial density (P<0.001). This quantitative study reveals decreased corneal innervation, sensation, and basal epithelial density in keratoconus. The results of this study provide strong evidence that both the sub-basal nerves and the basal epithelium may be involved in the pathogenesis of keratoconus, although it is uncertain whether these are primary or secondary changes.


Delayed cholangitis resulting from a retained T-tube fragment encased within a stone: a rare complication.
Inserting a T-tube after choledochotomy for the removal of bile duct stones remains a time-honored practice. Biliary drainage after bile duct exploration has some advantages. It minimizes bile leakage, provides access for cholangiography, and removes occasional retained stones. The use of T-tubes also has been associated with significant complications. Biliary sepsis, bile duct trauma during removal, bile leakage leading to peritonitis, retention of a fragment, stricture formation after removal have been reported. We report an unusual case of cholangitis caused by a T-tube fragment within a large stone, occurring 11 years after bile duct exploration. A 39-year-old woman underwent common bile duct exploration with insertion of a T-tube. Cholangiography was normal, but as the T-tube was removed, its horizontal limb was missing. The patient failed to present for endoscopic removal a few weeks after surgery Five years later, she presented with recurrent biliary pains and a mild episode of cholangitis. This last episode was associated with severe pain and jaundice. After initial conservative treatment, endoscopic retrograde cholangiopancreatography was performed, and endoscopic removal of the fragment and stone material was successful. Despite the declining numbers of bile duct explorations in the laparoscopic era and the tendency to use transcystic drainage or primary closure of a choledochotomy, the T-tube will continue to be a useful tool in biliary surgery, subject to consideration of the indications and the available alternatives. The reported case highlights the importance of careful tube preparation to prevent partial separation at removal, and early removal of a missing fragment to avoid potential serious complications.


Antimicrobial activity and conformation of gaegurin-6 amide and its analogs.
A function of the intra-disulfide bridge located at the C-terminal of Rana peptides has not been extensively studied. To investigate the function of the disulfide bridge related to the activity and the structure, we chose Gaegurin-6, isolated from Rana rugosa as a model peptide and synthesized linear analogs. The reduction of the disulfide bridge resulted in the complete loss of antimicrobial activity while replacements of cysteines by serines retained antimicrobial activity. Circular dichroism spectra from a titration of the peptides in sodium dodecyl sulfate indicated that the disulfide bridge of Gaegurin-6 might stabilize the induction of an alpha helical structure in lipid membranes and the alpha helical forming propensity of the peptides correlated with antimicrobial activity.


Kaempferol induces cell death through ERK and Akt-dependent down-regulation of XIAP and survivin in human glioma cells.
The present study was undertaken to determine the molecular mechanism by which kaempferol induces cell death in human glioma cells. Kaempferol resulted in loss of cell viability and inhibition of proliferation in a dose- and time-dependent manner, which were largely attributed to cell death. Kaempferol caused an increase in reactive oxygen species (ROS) generation and the kaempferol-induced cell death was prevented by antioxidants, suggesting that ROS generation is involved in kaempferol-induced cell death. Kaempferol caused depolarization of mitochondrial membrane potential. Western blot analysis showed that kaempferol treatment caused a rapid reduction in phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. The ERK inhibitor U0126 and the Akt inhibitor LY984002 increased the kaempferol-induced cell death and overexpression of MEK, the upstream kinase of ERK, and Akt prevented the cell death. The expression of anti-apoptotic proteins XIAP and survivin was down-regulated by kaempferol and its effect was prevented by overexpression of MEK and Akt. Kaempferol induced activation of caspase-3 and kaempferol-induced cell death was prevented by caspase inhibitors. Taken together, these findings suggest that kaempferol results in human glioma cell death through caspase-dependent mechanisms involving down-regulation of XIAP and survivin regulating by ERK and Akt.


Early changes in myocardial perfusion patterns after myocardial infarction: relation with contractile reserve and functional recovery.
The purpose of this study was to assess early temporal changes in myocardial perfusion pattern by myocardial contrast echocardiography (MCE) and their relation to myocardial viability in patients with reperfused acute myocardial infarction (AMI). Myocardial contrast echocardiography no-reflow is associated with poor contractile recovery after AMI. However, little is known regarding early reversibility of microvascular dysfunction and its relation to myocardial viability. Intracoronary MCE was performed immediately after reflow and 9 days later in 28 patients with a first AMI and successful coronary recanalization (Thrombolysis in Myocardial Infarction trial grade 3 flow). Semiquantitative contrast score and wall motion score (WMS) were assessed in each initially asynergic segment at initial and repeat MCE study. Low dose dobutamine echocardiography (DE) was performed at day 10, and follow-up (FU) rest echocardiography was performed 6 weeks later. Among 200 initially asynergic segments, 49% exhibited no or heterogeneous contrast enhancement at initial MCE versus 24% at restudy (p < 0.001). Three groups of segments were defined according to early changes in contrast pattern: group A, "sustained no-reflow" (n = 17); group B, improved contrast score (n = 68), and group C, "sustained reflow" (n = 112). Group A segments showed no improvement in WMS at FU. In contrast, group B segments showed significant improvement in WMS at FU (p < 0.0001), and exhibited more frequently contractile reserve at DE (36% vs. 6%, p = 0.02) and contractile recovery at FU (34% vs. 7%, p = 0.03) than group A segments. Group C segments exhibited contractile reserve and contractile recovery in 47% and 51% of segments respectively. Improvement in MCE perfusion pattern may occur after initial no-reflow in the days following reperfused AMI and is associated with preservation of contractile reserve and gradual regional functional recovery.


Complete nucleotide sequence of the cucumber necrosis virus genome.
The complete nucleotide sequence of the cucumber necrosis virus (CNV) genome has been determined. The genome is 4701 nucleotides in length and contains five long open reading frames (ORF). ORF1 begins at the first AUG codon at the 5' terminus and terminates at an amber codon. The predicted molecular weight of the polyprotein encoded by ORF1 is 33 kilodaltons (kDa). Readthrough of the ORF1 amber codon would yield a protein with a molecular weight of 92 kDa. Comparison of the amino acid sequence of the 92-kDa protein with the putative replicases of carnation mottle virus (CarMV) and barley yellow dwarf virus (BYDV) shows extensive sequence similarity. This suggests that the CNV 92-kDa protein is the viral replicase and, furthermore, suggests a close evolutionary relationship between CNV, CarMV, and BYDV, members of the Tombus-, Carmo-, and Luteovirus groups, respectively. Immediately following the 92-kDa protein is ORF3 which can encode a 40-kDa protein. It is identified as the coat protein based on its similarity in amino acid composition to the previously determined CNV coat protein sequence (J. H. Tremaine, 1972, Virology 48, 582-590) and on its amino acid sequence similarity with the tomato bushy stunt virus coat protein. Two nested ORFs (ORF4 and -5), in different frames, follow the coat protein gene. Although it is not known if both ORFs are expressed, they would encode proteins with predicted molecular weights of 21 and 20 kDa, respectively.


Renin inhibitors: novel agents for renoprotection or a better angiotensin receptor blocker for blood pressure lowering?
Aliskiren, the first in a new class of orally effective direct renin inhibitors (DRIs) was recently approved for the treatment of hypertension. In this review, we discuss the history of the development of DRIs and available data regarding the effects of DRIs in the treatment of hypertension and related target organ damage.


[Nebulized salbutamol as a possible cause of lactate acidosis in a patient with acute asthma].
A 50-year-old man was in the emergency department treated for acute asthma with repeated doses of nebulized salbutamol according to guidelines, and as a result of this treatment he developed marked lactate acidosis. Lactate acidosis is not commonly listed as a side effect to nebulized salbutamol. House officers in the emergency department handling acute asthma should be aware of this paradox, though the condition may resolve in spite of continued treatment with salbutamol.


Battered gay men: an exploration of abuse, help seeking, and why they stay.
In comparison to a large body of literature about battered heterosexual women and a growing body about battered lesbians, this is one of the first published studies that investigates the experiences of battered gay and bisexual men. Results indicated that these men suffered patterns, forms, and frequencies of physical, emotional, and sexual abuse similar to what has been documented by research on battered heterosexual and lesbian women. Likewise, the most commonly reported reasons for staying--namely, hope for change and love for partner--appear to be universal to the experience of being battered. Unlike battered heterosexual women, respondents in this study were not likely to report that being financially trapped was a major reason why they had remained. HIV-status, however, appears to significantly influence their decision to remain. Moreover, lack of knowledge about domestic violence and the lack of availability of appropriate resources play a significant role in same-gender domestic violence victims' decisions to remain. Like battered lesbians, battered gay men infrequently sought assistance from battered women's services and perceived these services as not helpful. By contrast, individual counselors and agencies who provided individual counselors were rated as quite helpful.


Depth perception in cats after cerebral hemispherectomy: comparisons between neonatal- and adult-lesioned animals.
Depth perception was studied in adult cats following removal of the left cerebral hemisphere as a neonate or as an adult. Both monocular and binocular thresholds were determined using a visual cliff. Although both age-at-lesion groups showed depth perception deficits, the neonatal-lesioned animals performed much worse under binocular conditions on the visual cliff than either adult-lesioned or intact animals. This was primarily due to the lack of a binocular advantage in the neonatal-lesioned cats since their monocular thresholds were similar to that of adult-lesioned animals. Both lesioned groups showed higher monocular thresholds compared to intact animals but this effect reached significance only for the right eye. In addition, the neonatal-lesioned cats showed ocular misalignment which may have contributed to their lack of binocular depth perception. Regardless of these deficits neonatal-lesioned cats were more like intact controls regarding the types of errors made on the visual cliff. Neonatal-lesioned animals and intact controls made random errors, whereas adult-lesioned animals made most of their errors when the shallow shelf was presented on the animals' right side. This may indicate that the adult-lesioned animals have greater motor and/or visual field biases than do neonatal-lesioned cats.


Synthesis of a thymine-functionalized nucleoamino acid for the solid phase assembly of cationic nucleopeptides.
In this work, we report the synthesis of a thymine-functionalized nucleoamino acid suitable for the solid phase synthesis of nucleopeptides. The monomer was obtained in solution starting from commercial compounds and after NMR ((1)H and (13)C) and ESIMS (positive ions) characterization it was used for the assembly of a cationic nucleopeptide obtained by sequentially introducing underivatized L-lysine units and nucleoamino acid monomers. After detachment from the resin, performed in acidic conditions, the oligomer was purified by HPLC and characterized by LC-ESIMS (positive ions) which confirmed the identity of the thymine-based nucleopeptide. The cationic nucleobase-containing peptide, well soluble in water, was studied by CD spectroscopy which allowed us to exclude any helical pre-organization of the nucleopeptide in the experimental conditions used. Furthermore, CD behavior of the oligomer at different temperatures was also studied as described in this work.