Staff and patients have mostly positive perceptions of physiotherapists working in emergency departments: a systematic review.
What are staff and patients' perceptions of physiotherapists working in the emergency department (ED)? Systematic review of qualitative studies. Staff working in EDs and patients presenting to the ED and managed by ED physiotherapists. Perceptions of ED staff and patients were synthesised using a three-stage thematic analysis consisting of extraction, grouping (codes), and abstraction of findings. Eight studies, which had sought the perceptions of 138 patients and 122 ED staff members, were included. Three main themes emerged: role of physiotherapists in the ED, positive perceptions of ED physiotherapists, and concerns about physiotherapists in the ED. Patients and ED staff both considered physiotherapists to be experts in musculoskeletal care. The role of ED physiotherapists was seen as providing thorough patient education, non-pharmacological pain management and activity resumption, especially through exercise therapy. Having broad knowledge to assess and treat different health conditions was seen as facilitating the work of physiotherapists in the ED. Patients and ED staff felt that ED physiotherapists had good interpersonal communication skills. ED staff expressed concerns regarding the additional time that physiotherapists spent with patients. Some patients felt that performing exercises in the ED was inappropriate and painful. ED physiotherapists were mostly well accepted by patients and ED staff, and their work was perceived to improve the ED. Concerns included restricted availability, lack of awareness of the role undertaken by physiotherapists in the ED, and increased treatment time in some settings. [Ferreira GE, Traeger AC, O'Keeffe M, Maher CG (2018) Staff and patients have mostly positive perceptions of physiotherapists working in emergency departments: a systematic review. Journal of Physiotherapy 64: 229-236].


Formulation of spinel based inkjet inks for protective layer coatings in SOFC interconnects.
In this study, inkjet printing technology was adopted for the application of protective layer coatings on metallic Solid Oxide Fuel Cell (SOFC) interconnects. The study highlights the potential of the inkjet printing process to fabricate aqueous-based protective layer coatings over ferritic stainless steels, a novel, very flexible, and low-cost approach to coating. The work presented focusses on the formulation of aqueous-based spinel particulate inks for the inkjet printing process using an electro-magnetic inkjet printer. An ink formulation route based on a two-stage ball milling technique was developed to produce a printable ink composition with Manganese Cobalt Oxide (MnCo2O4,MCO) and Manganese Cobalt Ferrite (MnCo1.8Fe0.2O4, MCF) as the coating materials. Stability of the ink suspensions and particle size distribution were studied and characterised using zeta and a particle size analysis, respectively. Flow properties of the inks were analysed using a conventional rheometer at shear rates 1 to 1000 s-1 and Piezo Axial Vibrator rheometer at higher shear rates (10-6 s-1). Finally, printability of the inks was assessed theoretically based on the Ohnesorge number, Z. The formulated MCO and MCF inks with ~ 25 wt% solid loading exhibited Z values of 4.17 and 6.77, satisfying the printability criteria of the inkjet inks. Printability of the inks was demonstrated by printing them on stainless-steel substrates. and printed layers were free of any visible defects after heat-treatment. The demonstrated ink formulation procedure provides a guide for inkjet inks development with respect to inkjet printer requirements. Furthermore, the outlined methodology can be employed to fabricate protective and other coatings for any kind of metallic components such as bipolar plates and heat-exchangers.


Effect of rapid mobilization on ejection fractions and ventricular volumes after acute myocardial infarction.
Despite the current practice of early mobilization and early hospital discharge after uncomplicated acute myocardial infarction (AMI), physicians are reluctant to permit normal physical and social activity for several weeks after the AMI "to allow the heart to heal." This study tested whether it was possible to identify a low risk group of patients on day 3 after AMI, and whether vigorous early mobilization from days 4 through 7 affected left ventricular function and volumes (studied by gated blood pool scan on days 4 and 14). There was 1 death in 3 months in 45 patients with uncomplicated AMI suitable for randomization to activity (group A) compared with 11 deaths in 55 patients unsuitable for rapid early mobilization (group B) (p less than 0.01). Early vigorous mobilization in 24 of the group A patients compared with sedentary care in 20 did not affect change in ejection fraction, end-diastolic volume, end systolic-volume, stroke volume, heart rate or cardiac output between days 4 and 14. A very low risk group suitable for early vigorous mobilization can be defined on day 3 after AMI; further, vigorous early mobilization does not affect left ventricular function or volumes. Early return to physical, social and occupational activity after uncomplicated AMI should result in marked reduction in direct and indirect costs of AMI.


Pentylenetetrazol kindling in rats: Is neurodegeneration associated with manifestations of convulsive activity?
Structural changes in neurons and measures of oxidative stress were studied in the hippocampus of rats tolerant (ST) and sensitive (SS) to developing clonic-tonic seizures in conditions of pentylenetetrazol kindling. Sequences of 11 injections of pentylenetetrazol significantly decreased the number of normal neurons in hippocampal field CA1 in SS rats, this effect being seen in both hippocampal field CA1 and the dentate fascia in ST rats. Decreases in the numbers of normal neurons were accompanied by increases in the numbers of damaged cells in field CA4 in rats of both groups. After 21 injections, decreases in the numbers of normal neurons were seen in field CA1 in both SS and ST rats, while the numbers of damaged neurons were significantly greater than control only in ST rats in fields CA1 and CA4. The glutathione level was significantly lower in the hippocampus in both groups of rats than in controls. Thus, rats " tolerant" to developing convulsions show signs of oxidative stress and neurodegenerative changes in the hippocampus. This suggests that oxidative neuron damage leading to neurodegeneration in the pentylenetetrazol kindling model is not directly associated with convulsive activity.


Perioperative Management of a Patient With von Recklinghausen's Disease With Anticipated Difficult Airway Management: A Case Report.
Von Recklinghausen's disease is characterized by skin pigmentation, multiple neurofibromatosis, and osseous changes. In the anesthetic management of patients with von Willebrand's disease, it is important to provide appropriate airway management, taking into account the cutaneous laxity caused by neurofibromatosis of Recklinghausen's disease. This case describes the perioperative management of a patient with Recklinghausen's disease with suspected difficulty in airway management.


The satiety factor oleoylethanolamide impacts hepatic lipid and glucose metabolism in goldfish.
Oleoylethanolamide (OEA) is an acylethanolamide synthesized mainly in the gastrointestinal tract with known effects in mammals on food intake and body mass through activation of peroxisome proliferator-activated receptor type α (PPARα). Since we previously demonstrated that acute treatment with OEA in goldfish resulted in decreased food intake and locomotor activity, as in mammals, we hypothesize that OEA would be involved in the control of energy metabolism in fish. Therefore, we assessed the effects of acute (for 6 h) and chronic (for 11 days) treatments with OEA (5 µg g-1 body mass) on metabolite concentrations and enzyme activities related to glucose and lipid metabolism in liver of goldfish (Carassius auratus). In the chronic treatment, OEA impairs the increase in body mass and reduces locomotor activity, without any signs of stress. The lipolytic capacity in liver decreased after both acute and chronic OEA treatments, whereas lipogenic capacity increased after acute and decreased after chronic treatment with OEA. These results are different from those observed to date in mammalian adipose tissue, but not so different from those known in liver, and might be attributed to the absence of changes in the expression of pparα, and/or to the increase in the expression of the clock gene bmal1a after chronic OEA treatment. As for glucose metabolism, a clear decrease in the capacity of hepatic tissue to use glucose was observed in OEA-treated fish. These results support an important role for OEA in the regulation of liver lipid and glucose metabolism, and could relate to the metabolic changes associated with circadian activity and the regulation of food intake in fish.


Factors that contribute to resistant forms of hypertension. Pharmacological considerations.
Treatment failure may be caused by induction of compensatory mechanisms that compromise effectiveness of the antihypertensive regimen. Antihypertensive agents have been classified according to mechanism of action, and compensatory mechanisms usually evoked by each class of drugs have been reviewed. Host factors may be responsible for the inability to control blood pressure or may predict special sensitivity or contraindication to a particular class of antihypertensive agents. Recommendations have been made for modification of stepped-care regimens and selection of initial antihypertensive agents based on host factors. Experimental evidence suggests the ability to target antihypertensive therapy in a manner that will prevent or reverse specific end-organ damage. Clinical studies are needed to define the long-term benefit derived from aggressive target organ protection.


A convenient thin layer chromatographic method for the detection of cyclochlorotine and simatoxin, toxins from Penicillium islandicum Sopp.
A rapid, convenient TLC method is described for detection of cyclochlorotine, a carcinogen produced by the commonly found storage mold Penicillium islandicum Sopp. This method has also led to the isolation of a new toxic metabolite, simatoxin.


Fucose decorated solid-lipid nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics.
The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanoparticles (SLNs) to target breast cancer. The developed nano-carriers were characterized with respect to particle size, PDI, zeta potential, drug loading and entrapment, in-vitro release etc. The characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, biodistribution, changes in tumor volume and animal survival. The ex-vivo results showed greater cellular uptake and better cytotoxicity at lower IC50 of methotrexate in breast cancer cells. Further, we observed increased programmed cell death (apoptosis) with altered lysosomal membrane permeability and better rate of degradation of lysosomal membrane in-vitro. On the other hand, in-vivo evaluation showed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs with formulated and anchored nano-carrier when compared with free drug. Moreover, sizeable reduction in tumor burden was estimated with fucose decorated SLNs as compared to that seen with free MTX and SLNs-MTX. Fucose decorated SLNs showed promising results to develop therapeutic interventions for breast cancer, and paved a way to explore this promising and novel nano-carrier which enables to address breast cancer.


[The role of cystatin in neoplastic progression and diagnosis].
Possible role of the cystatins, natural and specific inhibitors of the cysteine peptidases in cancer invasion is described. The value of cystatins determinations in serum and tissue extracts as diagnostic and prognostic parameters in human cancers is also presented.


Calcium oxalate and calcium phosphate capacities of cardiac sarcoplasmic reticulum.
Both oxalate-supported and phosphate-supported calcium uptake by canine cardiac sarcoplasmic reticulum initially increase linearly with time but fall to a steady-state level within 20 min. The departure from linearity could be due to a decrease in influx or to an increase in efflux of calcium. Because Ca2+-ATPase activity is linear, a decrease in the influx of calcium is an unlikely cause of the non-linear calcium uptake curves. A possible cause of an increase in calcium efflux is rupture of the vesicles. This hypothesis was tested by investigating the amount of calcium which could be released upon addition of 5 mM EGTA. The amount of rapidly releasable calcium was zero until a threshold calcium uptake of about 4-6 mumol calcium oxalate or calcium phosphate per mg was reached. After that point the rapidly releasable calcium continued to increase with calcium oxalate to reach more than 23 mumol/mg, but stayed constant at about 0.7 mumol/mg for calcium phosphate. The rapidly releasable calcium was attributed to calcium oxalate or calcium phosphate crystals externalized by vesicle rupture. The differences in the amounts of rapidly releasable calcium were attributed to different kinetics of calcium phosphate and calcium oxalate dissolution. Addition of ryanodine caused a marked increase in the threshold for rapidly releasable calcium oxalate. Transmission electron micrographs showed that vesicles can become filled with calcium oxalate crystals, but the vesicles were heterogeneous with respect to their size and their sensitivity to ryanodine. These observations support the hypothesis that calcium oxalate and calcium phosphate capacities are limited by vesicle rupture and that ryanodine increases the capacity by closing a calcium channel in a subpopulation of vesicles that otherwise would not accumulate calcium.


Evaluating the Role of Microbial Internal Storage Turnover on Nitrous Oxide Accumulation During Denitrification.
Biological wastewater treatment processes under a dynamic regime with respect to carbon substrate can result in microbial storage of internal polymers (e.g., polyhydroxybutyrate (PHB)) and their subsequent utilizations. These storage turnovers play important roles in nitrous oxide (N2O) accumulation during heterotrophic denitrification in biological wastewater treatment. In this work, a mathematical model is developed to evaluate the key role of PHB storage turnovers on N2O accumulation during denitrification for the first time, aiming to establish the key relationship between N2O accumulation and PHB storage production. The model is successfully calibrated and validated using N2O data from two independent experimental systems with PHB storage turnovers. The model satisfactorily describes nitrogen reductions, PHB storage/utilization, and N2O accumulation from both systems. The results reveal a linear relationship between N2O accumulation and PHB production, suggesting a substantial effect of PHB storage on N2O accumulation during denitrification. Application of the model to simulate long-term operations of a denitrifying sequencing batch reactor and a denitrifying continuous system indicates the feeding pattern and sludge retention time would alter PHB turnovers and thus affect N2O accumulation. Increasing PHB utilization could substantially raise N2O accumulation due to the relatively low N2O reduction rate when using PHB as carbon source.


Characterization of neutrophil alkaline phosphatase-inducing factor (NAP-IF).
A factor, termed neutrophil alkaline phosphatase-inducing factor (NAP-IF), that has the capacity to increase the NAP activity of granulocytes was characterized by using two samples: cystic fluid (CF) and conditioned medium of a tumor cell line (T3M5). The molecular weight of NAP-IF was shown to be between 13,000 and 45,000, and its isoelectric point was between 5.5 and 6.2. It was sensitive to heat and proteolytic enzymes, but was resistant to DNase and RNase, suggesting that NAP-IF is an acidic protein or glycoprotein. These characteristics of NAP-IF seem to be similar to those of granulocyte-macrophage colony-stimulating factor (GM-CSF) that is also present in the CF. NAP-IF rich fractions obtained by isoelectric focusing from CF were also found to be rich in a subclass of GM-CSF: granulocyte-CSF (G-CSF). Furthermore, a high correlation was noted between the activities of G-CSF and NAP-IF (gamma = 0.798, P less than 0.005). These results suggest that the two activities, i.e., G-CSF and NAP-IF, may be attributable to an identical macromolecule.


Glutathione S-transferase SlGSTE1 in Spodoptera litura may be associated with feeding adaptation of host plants.
Spodoptera litura is polyphagous pest insect and feeds on plants of more than 90 families. In this study the role of glutathione S-transferase epilson 1 (slgste1) in S. litura in detoxification was examined. This gene was up-regulated in the midgut of S. litura at the transcriptional and protein levels when the insect fed on Brassica juncea or diet containing phytochemicals such as indole-3-carbinol and allyl-isothiocyanate that are metabolic products of sinigrin and glucobrassicin in B. juncea. The SlGSTE1 could catalyze the conjugation of reduced glutathione and indole-3-carbinol and allyl-isothiocyanate, as well as xanthotoxin, which is a furanocoumarin, under in vitro condition. When the expression of Slgste1 in the larvae was suppressed with RNAi, the larval growth and feeding rate were decreased. Furthermore, the up-regulated expression of the SlGSTE1 protein in the midgut of larvae that fed on different host plants was detected by 2-DE and ESI/MS analysis. The feeding adaptation from the most to the least of the larvae for the various host plants was Brassica alboglabra, Brassica linn. Pekinensis, Cucumis sativus, Ipomoea batatas, Arachis hypogaea and Capsicum frutescens. All the results together suggest that Slgste1 is a critical detoxifying enzyme that is induced by phytochmicals in the host plants and, inter alia, may be related to host plant adaptation of S. litura.


Effects of adolescent ethanol exposure on ethanol consumption in adult rats.
Ethanol exposure during early development could predispose an individual to increased ethanol consumption. Given the high prevalence of adolescent ethanol abuse, it is important to assess the potential impact of adolescent ethanol exposure on the development of alcohol drinking. The following study was designed to assess the initiation of ethanol consumption in adult rats after exposure to ethanol vapors during adolescence. Male Sprague-Dawley rats (n = 23) were exposed to ethanol vapor for 12 h per day for 10 consecutive days between postnatal days 30 and 40. Ethanol vapor exposure maintained blood ethanol levels averaging 250 mg/dl. All rats were subsequently trained to self-administer ethanol after a 52-day withdrawal period. When ethanol consumption was assessed in the adult rats (>3 months old) there were no significant differences in initiation or maintenance of ethanol self-administration between ethanol-exposed and control rats. In addition, there were no group differences in the ability of a noise stressor presented before the drinking session to transiently decrease ethanol intake. Overall, these findings indicate that forced exposure to ethanol vapor during adolescence does not seem to be sufficient to alter initiation or maintenance of limited-access ethanol self-administration.


Ovarian secretion of pregnane compounds at first ovulation in rats treated with pregnant mare's serum gonadotropin.
Progesterone, 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-OH), 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-DHP), 20 alpha-hydroxy-5 alpha-pregnan-3-one (20 alpha, 5 alpha), and 5 alpha-pregnane-3 alpha, 20 alpha-diol (DIOL) in ovarian venous plasma at first ovulation in female rats treated on day 30 with 10 IU of pregnant mare's serum gonadotropin (PMSG) were assayed using gas chromatography. Progesterone peaked at late proestrus before ovulation (day 32) and at early diestrus after ovulation (day 34). With the first peak, 5 alpha-DHP and 3 alpha-OH increased. The 20 alpha-DHP level peaked at early diestrus after ovulation (day 34) and remained high thereafter. The 20 alpha, 5 alpha and DIOL peaked at estrus after ovulation (day 33) and then fell slowly. Injection of 2 micrograms of luteinizing hormone (LH) before sample collection increased secretion of 20-keto-pregnane compounds, except when they were at peak levels. The secretion of 20 alpha-hydroxy-pregnane compounds was unaffected by LH at all times tested. These results suggest that rat ovaries without corpora lutea secrete 20-keto-pregnane compounds in response to LH, but that 20 alpha-hydroxy-pregnane compounds are secreted only from ovaries with corpora lutea.


Neutrophil haptotaxis induced by the lectin KM+.
KM+ is a D-mannose binding lectin from Artocarpus integrifolia that induces neutrophil migration in vitro and in vivo. This attractant activity was shown to be caused by haptotaxis rather than chemotaxis. The inhibition by D-mannose of the neutrophil attraction exerted by KM+, both in vitro and in vivo, supports the idea that haptotaxis is triggered in vivo by the sugar binding sites interacting with glycoconjugates located on the neutrophil surface and in the extracellular matrix. In the present study an in vivo haptotaxis assay was performed by intradermally (i.d.) injecting 125I-KM+ (200 ng), which led to a selective staining of loose connective tissue and vascular endothelium. The radiolabelled area exhibited a maximum increase (five-fold) in neutrophil infiltration 3 h after injection, relative to i.d. 200 ng 125I-BSA. We characterized the ex vivo binding of KM+ to tissue elements by immunohistochemistry, using paraformaldehyde-fixed, paraffin-embedded, untreated rat skin. Bound KM+ was detected with an affinity-purified rabbit IgG anti-KM+ and visualized with an alkaline phosphatase based system. KM+ binding to connective tissue and vascular endothelium was inhibited by preincubating KM+ with 0.4 mM D-mannose and was potentiated by heparan sulfate (100 microg ml(-1)). An in vitro assay carried out in a Boyden microchamber showed that heparan sulfate potentiated the attractant effect of 10 microg KM+ by 34%. The present data suggest that KM+ induces neutrophil migration in vivo by haptotaxis and that the haptotactic gradient could be provided by the interaction of the KM+ carbohydrate recognition site(s) with mannose-containing glycoconjugate(s) in vascular endothelium and connective tissue. Heparan sulfate would act as an accessory molecule, enhancing the KM+ tissue binding and potentiating the induced neutrophil haptotaxis.


Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays.
Identifying novel and known genes that are differentially expressed in breast cancer has important implications in understanding the biology of breast tumorigenesis and developing new diagnostic and therapeutic agents. In this study we have combined two powerful technologies, PCR-based cDNA subtraction and cDNA microarray, as a high throughput methodology designed to identify cDNA clones that are breast tumor- and tissue-specific and are overexpressed in breast tumors. Approximately 2000 cDNA clones generated from the subtracted breast tumor library were arrayed on the microarray chips. The arrayed target cDNAs were then hybridized with 30 pairs of fluorescent-labeled cDNA probes generated from breast tumors and normal tissues to determine the tissue distribution and tumor specificity. cDNA clones showing overexpression in breast tumors by microarray were further analysed by DNA sequencing, GenBank and EST database searches, and quantitative real time PCR. We identified several known genes, including mammaglobin, cytokeratin 19, fibronectin, and hair-specific type II keratin, which have previously been shown to be overexpressed in breast tumors and may play an important role in the malignance of breast. We also discovered B726P which appears to be an isoform of NY-BR-1, a breast tissue-specific gene. Two additional clones discovered, B709P and GABA(A) receptor pi subunit, were not previously described for their overexpression profile in breast tumors. Thus, combining PCR-based cDNA subtraction and cDNA microarray allowed for an efficient way to identify and validate genes with elevated mRNA expression levels in breast cancer that may potentially be involved in breast cancer progression. These differentially expressed genes may be of potential utility as therapeutic and diagnostic targets for breast cancer.


Dose-dependent effects of an immune challenge at both ultimate and proximate levels in Drosophila melanogaster.
Immune responses are highly dynamic. The magnitude and efficiency of an immune response to a pathogen can change markedly across individuals, and such changes may be influenced by variance in a range of intrinsic (e.g. age, genotype, sex) and external (e.g. abiotic stress, pathogen identity, strain) factors. Life history theory predicts that up-regulation of the immune system will come at a physiological cost, and studies have confirmed that increased investment in immunity can reduce reproductive output and survival. Furthermore, males and females often have divergent reproductive strategies, and this might drive the evolution of sex-specific life history trade-offs involving immunity, and sexual dimorphism in immune responses per se. Here, we employ an experiment design to elucidate dose-dependent and sex-specific responses to exposure to a nonpathogenic immune elicitor at two scales--the 'ultimate' life history and the underlying 'proximate' immune level in Drosophila melanogaster. We found dose-dependent effects of immune challenges on both male and female components of reproductive success, but not on survival, as well as a response in antimicrobial activity. These results indicate that even in the absence of the direct pathogenic effects that are associated with actual disease, individual life histories respond to a perceived immune challenge--but with the magnitude of this response being contingent on the initial dose of exposure. Furthermore, the results indicate that immune responses at the ultimate life history level may indeed reflect underlying processes that occur at the proximate level.


Hippocampal theta rhythms from a computational perspective: code generation, mood regulation and navigation.
In this paper three computer models are summarized discussing different functions of the cortico-hippocampal system. Mood regulation, rhythm and code generation and navigation are integrated into a coherent conceptual framework around the concepts of structural hierarchy and circular causality. First, a model of spatio-temporal code generation is reviewed in which the hippocampal population theta rhythm plays an important role. Next, generation and pharmcological modulation of this rhythm is examined using a computer model of multiple cell populations forming a feed-back loop within the hippocampus and between the septum and the hippocampus. Last, an abstract, but biologically motivated model of navigation is described which achieves a near optimal mode of navigation by composing hierarchical levels of the cortico-hippocampal system. The connections among the different hierarchical structures of the cortico-hippocampal organization and their functional roles are discussed.


Primary hypothyroidism with growth failure and pituitary pseudotumor in a 13-year-old female: a case report.
Primary hypothyroidism is a well-known cause of poor linear growth in children. A rare finding with profound or long-standing disease is anterior pituitary enlargement (pituitary pseudotumor). This case highlights this uncommon finding, discusses clinical situations in which gradual dose escalation of levothyroxine may be advisable and reviews adjuvant therapies that have been previously attempted to improve final height in the setting of profound hypothyroidism. We report the case of a 13-year-old Hispanic girl initially evaluated for poor linear growth and delayed puberty, and found to have pituitary enlargement secondary to profound primary hypothyroidism. Treatment with progressive doses of levothyroxine normalized her symptoms and led to complete resolution of her pituitary findings, but she then rapidly progressed through puberty, achieving an adult height of only 142cm, significantly below her calculated mid-parental height. In cases of severe primary hypothyroidism with prolonged elevation of thyroid-stimulating hormone and pituitary pseudotumor, gradual replacement of thyroid hormone with slowly escalating doses of levothyroxine may be beneficial to prevent complications of therapy. Early recognition and treatment of hypothyroidism during childhood is essential for normal growth, as final height is invariably compromised in children with prolonged disease. Additional study is needed to determine the potential beneficial effects of gonadotropin-releasing hormone agonist and recombinant human growth hormone treatment in this setting.


Clearing the MIST (metabolites in safety testing) of time: The impact of duration of administration on drug metabolite toxicity.
The importance of mass and concentration, rather than percentage, in determining the safety of risk of metabolites has been the subject of recent scholarship. These studies have not examined the dimension of time as represented by the duration of exposure to the chemical. Reviewing a wide range of clinical information duration of exposure is not a pivotal factor for most types of toxicity, particularly those classified as types A, B or C where concentration and mass are the primary considerations. For instance in idiosyncratic toxicity, classified as type B, where a reactive metabolite is implicated and an immune response is generally required, toxicity can occur early in treatment (1 week to 1 month after starting therapy). In contrast to this type D toxicity in particular carcinogenicity requires that duration of exposure is taken into consideration alongside mass and dose and should be considered the most critical factor. To elicit a response known human carcinogens need a duration of exposure of many years combined with an induction/latency period also measured in years. The perceived risk of a unique human metabolite as a potential health risk by carcinogenesis becomes exceedingly low when the time scale for effect is compared with the age of patients undergoing therapy and their duration of treatment.


Enhanced color flow imaging of breast cancer vasculature: continuous wave Doppler and three-dimensional display.
Two methods of potentially improving the detection and assessment of breast cancer vasculature by color flow Doppler ultrasonography were studied. Use of continuous wave (CW) Doppler imaging was one method evaluated by a comparison of system sensitivity to small vessel flow by continuous wave and pulsed Doppler methods. The second technique demonstrated color flow image acquisition and three-dimensional (3D) display. Six breast cancer patients were examined with both a color flow pulsed system and a CW Doppler system employing a hand-held transmitter-receiver pair with crossed-beam patterns. The CW unit consistently revealed more regions of tumor flow and multidirectional flow. Good 3D displays were achieved on larger pulsatile vessels, from images obtained during systole and selected for minimal noise.


Radioimmunoassayable prostate-specific acid phosphatase in peripheral and bone marrow sera compared in diagnosis of prostatic cancer patients.
Measurements of human prostate-specific acid phosphatase by radioimmunoassay in peripheral and bone marrow sera were compared. We studied 20 patients with benign prostatic hyperplasia, 27 with untreated prostatic cancer without bone metastases and 11 with metastases, in addition to 7 with cancer treated by hormonal therapy. The prostate-specific acid phosphatase concentrations in peripheral and bone marrow serum samples were equal and did not exceed the upper limit of our health-associated reference interval, 2.8 microgram. per 1. (mean plus 2 standard deviations) in patients with prostatic hyperplasia. Of 27 prostatic cancer patients without bone metastases the concentration of prostate-specific acid phosphatase was elevated in the peripheral sera of 20 and in the bone marrow sera of 21, and 21 had an extracapsular tumor (stage T3 to T4). Prostate-specific acid phosphatase concentrations were elevated in peripheral and bone marrow serum specimens of all 11 patients with metastases and bone marrow cytology studies were positive in 2. There was no difference in prostate-specific acid phosphatase concentrations in peripheral and bone marrow serum specimens from prostatic cancer patients undergoing hormonal treatment. We conclude that the use of bone marrow serum for the measurement of radioimmunoassayable prostate-specific acid phosphatase in prostatic cancer patients does not provide any further information in regard to the detection of prostatic cancer compared to the use of peripheral serum specimens. Falsely positive findings in bone marrow specimens were not observed with the method used.


Quality of life after traumatic thoracolumbar spinal cord injury: a North Indian perspective.
Cross-sectional study. To determine the Quality of Life (QOL) in individuals with traumatic Spinal Cord Injury (SCI) of thoracolumbar region in Indian population, the factors affecting QOL and to compare this to other SCI populations. Tertiary level hospital in low-middle income country. 93 individuals with SCI of minimum 1 year duration since injury were included in the study. Baseline demographics, socioeconomic parameters, and incidence of complications were ascertained. World Health Organisation Quality of Life-BREF (WHOQOL-BREF) score was used for measurement of QOL and was then compared to healthy Indian population and other SCI studies. Subgroup analysis was done to find out impact of variables on different domains of WHOQOL-BREF. The median (IQR) age of the study participants was 35 (25, 45) with a male predominance. The median (IQR) duration since injury in the study population was 50 (26, 70) months. Lowest mean (SD) score was observed in the psychological domain -50.3 (12.1) and comparison to healthy Indian and high-income SCI populations revealed drastically decreased scores across all domains (p < 0.01). Employed individuals and housewives had significantly higher scores across all domains than unemployed individuals (p < 0.05). American Spinal Injury Association Impairment Scale (AIS) grade, socioeconomic status, pain and presence of complications all had significant impact on domain scores (p < 0.05). Multiple regression analysis revealed that mobilisation status and pain had the greatest effect on QOL. Individuals with SCI have low QOL scores as compared to general Indian population as well as SCI individuals from a high resource setting. Pain and dependent mobilisation were found to be most significant predictors of poor WHOQOL-BREF domain scores. Housewives were found to have domain scores comparable to employed individuals. Presence of complications negatively impacts QOL.


The surgical treatment of blepharoptosis in oculomotor nerve palsy.
We reviewed retrospectively 170 cases of congenital and acquired oculomotor nerve palsy to determine the effectiveness of surgery in the treatment of blepharoptosis in oculomotor nerve palsy. Twenty patients had had surgical repair of the blepharoptosis. Patients with congenital oculomotor palsy were more often selected for blepharoptosis surgery than patients with acquired blepharoptosis because of the absence of diplopia caused by suppression in congenital cases. There was complete recovery in 72 of 109 patients (66%) with acquired oculomotor palsy. Results were judged with regard to functional improvements and cosmetic improvement. Primary functional disability was relieved by lifting the eyelid above the pupil in ten of 12 patients (83%). Primary cosmetic disability was relieved in six of six patients. Corneal complications occurred in six of 20 patients (30%) who were treated surgically.


Clonally unrelated Hodgkin's disease following autologous stem cell transplant for B-cell lymphoma.
Lymphoproliferative disorders after autologous stem cell transplantation (SCT) are rare. We describe two cases of Hodgkin's disease (HD) as a late secondary neoplasia following autologous SCT for mantle cell lymphoma and B-cell chronic lymphocytic leukaemia respectively. Both HD cases were of mixed cellularity type, showed Epstein-Barr virus (EBV) positivity and followed an aggressive course. Clonal analysis of rearranged immunoglobulin genes from the primary B-cell neoplasm and the secondary HD provided evidence of separate clonal origins of the two tumours in both patients, thus excluding secondary transformation of the original B-cell clone through EBV as the causative event for development of HD.


Biochemical changes in the central nervous system with age in the rat.
Studies dealing with biochemistry of the central nervous system of rats have been reviewed. Data on the effects of age on enzyme activity and cellular substrates have been summarized in tabular form. In general, it can be concluded that biochemical functions dealing with anabolism decrease whereas those dealing with catabolism increase as aging progresses.


Lateral and central presentation of words with limited exposure duration as remedial training for reading disabled children.
In two studies it is examined whether lateral presentation of words in remedial practice for reading disabled children has additional effects to central presentation. The effect of limited exposure duration (LED) is also studied as a possible factor in inducing higher level decoding processes or increased processing speed of words. Two groups of Dutch reading disabled children (n1 = 25, mean age = 9;8 years and n2 = 36, mean age = 7;1 years) repeatedly practiced reading words presented in the left, right or the central visual field. The results show that all children improved substantially both in reading speed and accuracy, which demonstrates the importance of repetitive practice in reading to attain fluency in reading disabled children. Further analysis demonstrated that neither site of presentation nor limited exposure duration added significantly to the training results. These findings do not corroborate neuropsychological theories suggesting a special role for lateral presentations.


Blood graft composition after plerixafor injection in patients with NHL.
Plerixafor is used to mobilize CD34(+) hematopoietic stem cells from bone marrow to circulation. Limited data are available in regard to graft cellular content collected after plerixafor. The aim of this study was to assess effects of plerixafor added to chemomobilization on graft CD34(+) cell subclasses, lymphocyte subsets, engraftment, and post-transplant course in non-Hodgkin lymphoma (NHL) patients. Thirty-four patients with NHL were included. All patients received chemotherapy plus G-CSF to mobilize stem cells. Nineteen patients received plerixafor pre-emptively owing to poor mobilization or poor collection yields. The rest of the patients constituted the control group. Flow cytometric analyzes were performed from cryopreserved graft samples. Also, data on post-transplant engraftment and outcome were collected. The proportion of primitive stem cells (CD34(+) CD133(+) CD38(-) ) was significantly higher after the plerixafor injection when compared to the first collection in the control group. The amount of T cells (CD3(+) ), helper (CD3(+) CD4(+) ) T subsets, and suppressor (CD3(+) CD8(+) ) T subsets in the graft was all significantly higher in the plerixafor group. Also, the amount of NK cells (CD3(-) CD16/56(+) ) was higher. Engraftment after high-dose therapy was comparable between the groups, but leukocyte and platelet count at 6 months were higher in patients receiving plerixafor-mobilized grafts. Plerixafor, when used pre-emptively in addition to chemomobilization, seems to mobilize more primitive CD34(+) stem cells, T lymphocytes, and NK cells. Whether these differences are associated with immune reconstitution, long-term engraftment, or patient outcomes needs to be evaluated in larger patient groups with longer follow-up.


Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.
Although many types of neurological disorders and events have been described in association with antiphospholipid antibodies (aPL) and the antiphospholipid syndrome (APS), only ischaemic stroke is reasonably well established and accepted as a diagnostic criterion for the syndrome. We propose to evaluate, classify and rank the association of other neurological manifestations as possible, probable, or definite according to the data available from clinical studies and animal models. By these criteria, none of the neurological disorders or events such as epilepsy, psychiatric disease, dementia, transverse myelitis, multiple sclerosis-like disease, chorea, migraine, Guillian-Barrè syndrome, and sensory-neural hearing loss, can be definitely associated with aPL or APS.


Postural control during lifting.
Any voluntary motion of the body causes an internal perturbation of balance. Load transfer during manual material handling may increase these perturbations. This study investigates effects of stance condition on postural control during lifting. Nineteen healthy subjects repeatedly lifted and lowered a load between a desk and a shelf. The base of support was varied between parallel and step stance. Ground reaction force and segmental kinematics were measured. Load transfer during lifting perturbed balance. In parallel stance postural response consisted of axial movements in the sagittal plane. Such strategy was accompanied by increased posterior shear forces after lift-off. Lifting in step stance provided extended support in anterior/posterior direction. The postural control mechanisms in the sagittal plane are less complex as compared to parallel stance. However, lifting in step stance was asymmetrical and thus accompanied by distinct lateral transfer of the body. Lateral shear forces were larger as compared to parallel stance. Both lifting techniques exhibit positive and negative aspects. We cannot recommend either one as being better in terms of postural control.


Endorectal magnetic resonance imaging and magnetic resonance spectroscopy to monitor the prostate for residual disease or local cancer recurrence after transrectal high-intensity focused ultrasound.
To assess the role of magnetic resonance imaging (MRI) for evaluating changes in the prostate after transrectal high-intensity focused ultrasound (HIFU) for treating prostate cancer, correlating the findings with histology to assess its possible role in predicting the outcome, evaluating residual cancer or local recurrence of disease. Ten patients with prostate cancer were assessed with MR and MR spectroscopy (MRS) before and at 1, 4 and 12 months after HIFU, assessing the glandular volume and MRI and MRS data after HIFU. These data were correlated with the prostate-specific antigen (PSA) levels at each examination (suspicious for residual cancer if >0.5 ng/mL) and with histological findings of prostate biopsy sampling at 6-8 months (random or targeted at suspicious MR areas). Variations in volume during the follow-up were not associated with treatment outcome. MRI was suspicious for residual cancer in one patient at 1 month and in another two at 4 months; in all three patients (one with a PSA level of <0.5 ng/mL) targeted biopsies were positive for cancer. MRI was negative in seven patients; in six of these (one with a PSA level of >0.5 ng/mL) random biopsies were negative, and in one the random biopsies were positive for residual cancer. At 4 months there was a statistically significant difference (P = 0.015) between patients responsive to treatment and those with persistent disease, by combining negative MRI with a PSA level of <0.5 ng/mL; MRS data were suitable for analysis only in three patients with partial necrosis. Our preliminary data support the role of MRI in association with PSA levels as a useful and accurate tool in the follow-up of patients treated with HIFU for prostate cancer. However, considering the economic issue, it should not be used routinely and should be limited to detecting residual cancer (in patients with a PSA level of >0.5 ng/mL) with the main purpose of improving the detection rate of transrectal ultrasonography (TRUS)-guided prostate biopsy. MRS data had no additional value over MRI. Further evaluation is needed to compare the use of contrast media and other techniques (e.g. colour Doppler TRUS) in detecting residual or local recurrent cancer.


The multi-disciplinary role of 'pion factories'.
The multi-disciplinary role of intermediate energy proton accelerators in pure and applied nuclear physics is discussed with particular reference to the experimental programmes at LAMPF (Los Alamos Meson Physics Facility) and SIN (Swiss Institute for Nuclear Research, Zurich).


Chemodivergent photocatalytic access to 1-pyrrolines and 1-tetralones involving switchable C(sp3)-H functionalization.
A chemodivergent photocatalytic approach to 1-pyrrolines and 1-tetralones from alkyl bromides and vinyl azides has been developed through chemoselectively controllable intermolecular [3 + 2] and [4 + 2] cyclization. This photoredox-neutral two-component protocol involves intermolecular radical addition and switchable distal C(sp3)-H functionalization enabled by iminyl radical-mediated 1,5-hydrogen atom transfer. Meanwhile, chemoselectivity between C(sp3)-N bond formation and C(sp3)-C(sp2) bond formation is precisely switched by photocatalysts (Ru(bpy)3(PF6)2 vs. fac-Ir(ppy)3) and additives (base vs. acid).


A new family of cyclophilins with an RNA recognition motif that interact with members of the trx/MLL protein family in Drosophila and human cells.
A new family of cyclophilins with an RNA recognition motif (RRM) has members in vertebrates, roundworms and flatworms. We have identified a Drosophilacyclophilin, Dcyp33, with a high degree of amino acid sequence identity and similarity with other members of the family. Dcyp33 interacts through its RRM domain with the third PHD finger of trithorax. This interaction is conserved in the human homologues of these proteins, Cyp33 and MLL. Over expression of Dcyp33 in DrosophilaSL1 cells results in down-regulation of AbdominalB Hoxgene expression, mirroring the effect of human Cyp33 on the expression of human HOXgenes.


Nosocomial infections in intensive care unit in a Turkish university hospital: a 2-year survey.
To determine epidemiology and risk factors for nosocomial infections in intensive care unit (ICU). DESIGN. Prospective incidence survey. An adult general ICU in a university hospital in western Turkey. All patients who stayed more than 48 h in ICU during a 2-year period (2000-2001). The study included 434 patients (7394 patient-days). A total of 225 infections were identified in 113 patients (26%). The incidence and infection rates were 56.8 in 1000-patient days and 51.8%, respectively. The infections were pneumonia (40.9%), bloodstream (30.2%), urinary tract (23.6%) and surgical site infections (5.3%). Pseudomonas aeruginosa (22.6%), methicillin-resistant Staphylococcus aureus (22.2%) and Acinetobacter spp. (11.9%) were frequently isolated micro-organisms. Median length of stay with nosocomial infection and without were 13 days (Interquartile range, IQR, 20) and 2 days (IQR, 2), respectively ( P<0.0001). In logistic regression analysis, mechanical ventilation [odds ratio (OR): 16.35; 95% confidence interval (CI): 8.26-32.34; P<0.0001), coma (OR: 15.04; 95% CI: 3.41-66.33; P=0.0003), trauma (OR: 10.27; 95% CI: 2.34-45.01; P=0.002), nasogastric tube (OR: 2.94; 95% CI: 1.47-5.90; P=0.002), tracheotomy (OR: 5.77; 95% CI: 1.10-30.20; P=0.04) and APACHE II scores 10-19 (OR: 10.80; 95% CI: 1.10-106.01; P=0.04) were found to be significant risk factors for nosocomial infection. Rate of nosocomial infection increased with the number of risk factors (P<0.0001). Mortality rates were higher in infected patients than in non-infected patients (60.9 vs 22.1%; P<0.0001). These data suggest that, in addition to underlying clinical conditions, some invasive procedures can be independent risk factors for nosocomial infection in ICU.


The effect of occlusive dressings on collagen synthesis and re-epithelialization in superficial wounds.
The effects on superficial wounds in domestic pigs of (1) two different occlusive dressings, (2) non-occlusive wet to dry gauze dressings, and (3) air exposure were compared. Collagen synthesis and re-epithelialization were increased in the wounds treated with occlusive dressings. Re-epithelialization was increased beneath both the oxygen-impermeable and the oxygen-permeable dressing. When they were removed the wet to dry gauze dressing and one of the occlusive dressings often damaged the new epidermis.


In vitro anti-biofilm activity of 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata against Pseudomonas aeruginosa.
14-Deoxy-11,12-didehydroandrographolide is a biologically active molecule present in the extract of Andrographis paniculata (Kalmegh), a classic ethnic herbal formula, which has been used for over thousand years as therapeutics to treat numerous infectious diseases like upper respiratory tract infection, urinary tract infection, and many more health issues. The present study is designed to ascertain an inhibitor against biofilm formation from the major metabolites of Andrographis paniculata, because the extract of this herb shows inhibition of bacterial quorum sensing (QS) communication and biofilm development against microorganisms. 14-Deoxy-11,12-didehydroandrographolide at 0.1 mM (sub-MIC dose) with azithromycin (6 μg/mL, sub-MIC) or gentamicin (4 μg/mL, sub-MIC) synergistically inhibits 92% biofilm production by a 48-h treatment against Pseudomonas aeruginosa. Further investigation carried out by atomic force microscopy shows promising reduction in roughness and height of biofilm in the presence of 14-deoxy-11,12-didehydroandrographolide compared with the control group. The content of extracellular polymeric substances, level of pyocyanin production, and synthesis of extracellular protease by P. aeruginosa have also been reduced significantly at around 90% in 14-deoxy-11,12-didehydroandrographolide-treated group. In conclusion, 14-deoxy-11,12-didehydroandrographolide could be used as a drug molecule against biofilm development by inhibiting QS pathway in Pseudomonas aeruginosa.


Identification of the roasting reaction products of ferulic and sinapic acids and their xanthine oxidase inhibitory activity.
The roasting reaction products of ferulic and sinapic acids were analyzed using high-performance liquid chromatography (HPLC) and their constituent compounds were isolated. Structural analysis revealed that the major compounds were oligomers of the corresponding 4-vinylphenols. The xanthine oxidase (XO) inhibitory activity of the isolated compounds was also measured. Moderate XO inhibitory activity of some oligomers afforded from ferulic acid was observed.


Di-n-Butyl-, Tri-n-Butyl- and Triphenyltin dl-Terebates: Synthesis, Characterization and In Vitro Antitumour Activity.
Di-n-butyltin, tri-n-butyltin and triphenyltin terebates were screened against several human tumour cell lines and found comparably or more active than carboplatin, cis-platin, 5-fluorouracil, methotrexate and doxorubicin, some reference compounds used clinically.


Lessons from a clinic for the homeless. The Camillus Health Concern.
To present the educational opportunities provided by a model clinic for homeless persons. Descriptive. Patients are those who are cared for at Camillus Health Concern clinic for the homeless in Miami, Fla. Other participants include students, residents, and faculty affiliated with the University of Miami (Fla) School of Medicine. Affiliation of the clinic with the medical school has shifted the clinic from a pure service model to an education and service model. Numbers of patients and encounters are presented, as well as student and resident rotations, numbers, and hours. Shifting to an education and service model has increased productivity of the clinic while providing a unique, multifaceted educational experience to students, residents, and faculty. Those factors that contribute to the success of this education and service model include the professional satisfaction that results from providing care to patients who previously have not had access to health care; a team approach that includes faculty, students, nurses, and social workers; an environment that fosters clinical judgment rather than expensive tests; and the opportunity to teach social responsibility in the process of providing health care. We encourage other schools to consider the development of clinics for the homeless as alternative ambulatory training sites.


A randomized trial evaluating tobacco possession-use-purchase laws in the USA.
Tobacco Purchase-Use-Possession laws (PUP) are being implemented throughout the US, but it is still unclear whether they are effective in reducing smoking prevalence among the youth targeted by these public health policies. In the present study, 24 towns in Northern Illinois were randomly assigned to one of two conditions. One condition involved reducing commercial sources of youth access to tobacco (Control), whereas the second involved both reducing commercial sources of youth access to tobacco as well as fining minors for possessing or using tobacco (Experimental). Students in 24 towns in Northern Illinois in the United States completed a 74 item self-report survey in 2002, 2003, 2004 and 2005. At the start of the study, students were in grades 7-10. During each time period, students were classified as current smokers or nonsmokers (i.e., completely abstinent for the 30 consecutive days prior to assessment). The analyses included 25,404 different students and 50,725 assessments over the four time periods. A hierarchical linear modeling analytical approach was selected due to the multilevel data (i.e., town-level variables and individual-level variables), and nested design of sampling of youth within towns. Findings indicated that the rates of current smoking were not significantly different between the two conditions at baseline, but over time, rates increased significantly less quickly for adolescents in Experimental than those in Control towns. The implications of these findings are discussed.


The impact of previous ovarian surgery on ovarian reserve in patients with endometriosis.
To investigate the impact of previous ovarian surgery on ovarian reserve in patients with endometriosis. A total of 829 female patients were recruited. Their medical records were reviewed retrospectively. Patients who had diagnoses of endometriosis or endometrioma were defined as the endometriosis group, and those without endometriosis were as the control group. We further divided these patients into four groups according to whether they had received ovarian surgeries before. Group 1: control group without previous surgery; Group 2: control group with previous surgery; Group 3: endometriosis group without previous surgery; Group 4: endometriosis group with previous surgery. The subgroups with endometrioma or not and different operative procedures were also analyzed. The parameters for comparison included age, body mass index, serum estradiol, follicle-stimulating hormone, luteinizing hormone, cancer antigen 125, and anti-Müllerian hormone (AMH) level. The level of serum AMH was highest in group 1 and lowest in group 4. The decline was significant between group 1 and group 4 (p < 0.05). The serum AMH level was lower in group 4 than in group 3 but no significant difference. Serum estradiol level was significantly higher in group 3 than in group 2 (p < 0.05). Cancer antigen 125 levels were both significantly higher in group 3 and group 4 as compared with group 1 and group 2 (p < 0.05). Performing repeated ovarian surgery in patients with recurrent endometriosis needs careful consideration and adequate patient counselling because of the predictable deteriorating ovarian reserve.


Application of α-aminoisobutyric acid and β-aminoisobutyric acid inhibits pericarp browning of harvested longan fruit.
Pericarp browning is a critical problem resulting in reduced commercial value and shelf life of longan fruit. Two non-protein amino acids, α-aminoisobutyric acid (AIB) and β-aminoisobutyric acid (BAIB) at 100 and 1 mM were applied to longan fruit prior to storage for up to 8 days at 25 °C respectively. Contents of the major five phenolics (gallic acid, catechin, corilagin, epicatechin and gallocatechin gallate) were assayed by high-performance liquid chromatography (HPLC). Physiological properties related to pericarp browning of longan fruit were investigated during storage. Respiration rate, membrane permeability, malondialdehyde (MDA) content, and activities of polyphenol oxidase (PPO) and peroxidase (POD) were down-regulated by AIB or BAIB treatments, with significantly lower pericarp browning index and higher proportion of edible fruit than the control. Moreover, exogenous application of AIB and BAIB maintained higher contents of catechin, corilagin, epicatechin and gallocatechin gallate, but lower content of gallic acid compared to the control in the pericarp of longan fruit during storage, which was associated with the oxidation of browning substrate. Pericarp browning was inhibited and storage life of longan fruit was extended effectively by AIB and BAIB treatments with AIB treatment being more significant than BAIB. The findings may provide a new strategy for controlling pericarp browning of harvested longan fruit.


An optimized method for the accurate determination of patulin in apple products by isotope dilution-liquid chromatography/mass spectrometry.
Patulin, a mycotoxin produced by several molds in fruits, has been frequently detected in apple products. Therefore, regulatory bodies have established recommended maximum permitted patulin concentrations for each type of apple product. Although several analytical methods have been adopted to determine patulin in food, quality control of patulin analysis is not easy, as reliable certified reference materials (CRMs) are not available. In this study, as a part of a project for developing CRMs for patulin analysis, we developed isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC/MS/MS) as a higher-order reference method for the accurate value-assignment of CRMs. (13)C7-patulin was used as internal standard. Samples were extracted with ethyl acetate to improve recovery. For further sample cleanup with solid-phase extraction (SPE), the HLB SPE cartridge was chosen after comparing with several other types of SPE cartridges. High-performance liquid chromatography was performed on a multimode column for proper retention and separation of highly polar and water-soluble patulin from sample interferences. Sample extracts were analyzed by LC/MS/MS with electrospray ionization in negative ion mode with selected reaction monitoring of patulin and (13)C7-patulin at m/z 153→m/z 109 and m/z 160→m/z 115, respectively. The validity of the method was tested by measuring gravimetrically fortified samples of various apple products. In addition, the repeatability and the reproducibility of the method were tested to evaluate the performance of the method. The method was shown to provide accurate measurements in the 3-40 μg/kg range with a relative expanded uncertainty of around 1%.


[Value of sonography to monitor the course of Achilles tendon rupture after treatment--comparison of conservative therapy, percutaneous tendon adaptation, and open suture].
In this prospective study,73 patients (with an average age of 36 years) were examined by ultrasound to compare the results of open Achilles tendon surgery, percutaneous tendon adaptation, and conservative treatment. Once the accident reports had been collected, all of the patients presented themselves at the Sportklinik Stuttgart at intervals of 4, 8, 12, 26 weeks, and approx. 2.5 years after the accident. During the course of these examinations, the thickness and structure of the tendon was quantified via ultrasound and the quality by clinical examination. The results of the ultrasonic quantification of the healing process appeared to be similar in all patients. On the day of the accident the thickness of the tendon was 9.3 mm. Four weeks later a remarkable regeneration could be seen in all patients (12.0 mm), which reached a maximum (16.7 mm) after 26 weeks. By the end of the study, however, the result was a scarred and thickened tendon of 11.5 mm. The comparison of the ultrasound results and the clinical examination after 26 weeks and 2.5 years showed no correlation between the value of the echo structure and functionality of the tendon, and the comparison between the different therapy groups showed no significant difference in the healing process either. In conclusion, ultrasound examination is able to provide information concerning the stage of the healing process. The quality of the healing and healed Achilles tendon and the relationship to their function cannot be studied with ultrasound, and this is not influenced by the choice of therapy.


Cyclometalated iridium(III)-β-carboline complexes as potent autophagy-inducing agents.
Two cyclometalated Ir(III)-β-carboline complexes were identified as potent inducers of autophagic cell death. Autophagy induced by these complexes is ROS-mediated and caspase-independent.


Effects of anionic surfactants on hamster small intestinal membrane structure and function: relationship to surface activity.
The relationship of the surface properties of a group of anionic surfactants to their effects on intestinal water transport was studied. Dose-response inhibition of water transport in everted hamster jejunal segments was obtained with two long chain detergents (sodium dodecyl sulfate and dioctyl sodium sulfocuccinate), a fatty acid (ricinoleate), and dihydroxy bile salts (deoxycholate, chenodeoxycholate, and taurodeoxycholate), whereas no activity was seen with trihydroxy (cholate, glycocholate, and taurocholate) and tri-keto (dehydrocholate) bile salts. The relative effects on water transport were paralleled by their abilities to lyse the erythrocyte, a membrane model. These two biological effects were related to the surface properties of the agents, as determined by critical micelle concentration and surface tension reduction. We further characterized the action of deoxycholate on hamster small intestine, in vivo. Net water secretion was accompanied by increases in permeability of the mucosa to inulin, dextran, and albumin. These secretory and permeability changes were accompanied by both biochemical and histological alterations: exfoliation (DNA release), membrane effects (sucrase release), and shortened villi. Electron microscopy revealed extensive alteration of the brush border membrane with a decrease in binding of lanthanum and the development of permeability to tracer in villus tip cells. In contrast, taurocholate, which did not alter water transport, did not affect intestinal permeability or the brush border membrane. We believe that the surface properties of anionic surfactants cause changes in absorptive cell membranes which result in intestinal secretion.


'right@home': a randomised controlled trial of sustained nurse home visiting from pregnancy to child age 2 years, versus usual care, to improve parent care, parent responsivity and the home learning environment at 2 years.
By the time children start school, inequities in learning, development and health outcomes are already evident. Sustained nurse home visiting (SNHV) offers a potential platform for families experiencing adversity, who often have limited access to services. While SNHV programmes have been growing in popularity in Australia and internationally, it is not known whether they can improve children's learning and development when offered via the Australian service system. The right@home trial aims to investigate the effectiveness of an SNHV programme, offered to women from pregnancy to child age 2 years, in improving parent care of and responsivity to the child, and the home learning environment. Pregnant Australian women (n=722) are identified after completing a screening survey of 10 factors known to predict children's learning and development (eg, young pregnancy, poor mental or physical health, lack of support). Consenting women-surveyed while attending clinics at 10 hospitals in Victoria and Tasmania-are enrolled if they report having 2 or more risk factors. The intervention comprises 25 home visits from pregnancy to 2 years, focusing on parent care of the child, responsivity to the child and providing a good quality home learning environment. The standard, universal, Australian child and family health service provides the comparator (control). Primary outcome measures include a combination of parent-reported and objective assessments of children's sleep, safety, nutrition, parenting styles and the home learning environment, including the Home Observation of the Environment Inventory and items adapted from the Longitudinal Study of Australian Children. This study is approved by the Royal Children's Hospital Human Research Ethics Committees (HREC 32296) and site-specific HRECs. The investigators and sponsor will communicate the trial results to stakeholders, participants, healthcare professionals, the public and other relevant groups via presentations and publications. ISRCTN89962120, pre-results.


Aquagenic keratoderma associated with a mutation of the cystic fibrosis gene.
Reported for the first time in 1996, aquagenic keratoderma is a rare condition which is characterized by edematous flat-topped papules appearing on palmar skin after water immersion. Multiple anecdotal associations have been described but, recently, the association with cystic fibrosis gene mutations (CFTR) has been highlighted. The authors describe an 18 year-old female, with one-month complaints of pruritus and swelling of palmar skin after water immersion. On examination, palmar skin was unremarkable but, 5 minutes after water immersion, multiple whitish papules became apparent. CFTR genotype study showed a F508del mutation in one allele. She had no other symptoms and no relevant family history. Aquagenic keratoderma is probably an under-diagnosed entity that might represent a manifestation of CFTR mutations, making carrier state identification and genetic counseling possible.


Ligand internalization by cloned neuropeptide Y Y5 receptors excludes Y2 and Y4 receptor-selective peptides.
In human embryonic kidney-293 (HEK-293) cells, the cloned human neuropeptide Y Y5 receptor saturably internalized agonists, with the rank order of neuropeptide Y-(19-23)-[Gly1,Ser3,Gln4,Thr6,Ala31,Aib32,Gln34]human pancreatic polypeptide (neuropeptide Y-Aib-pancreatic polypeptide)>human neuropeptide Y>porcine peptide YY>[Pro34]human peptide YY>[Leu31,Pro34]human peptide YY>>human peptide YY-(3-36). Human pancreatic polypeptide competed [125I]neuropeptide Y binding and internalization in neuropeptide Y Y5 receptor-expressing cells, but itself showed no internalization. The internalization was strongly dependent on temperature. The surface binding, and especially the internalization, of human neuropeptide Y were highly sensitive to the clathrin network inhibitor phenylarsine oxide, and to the cholesterol-complexing antibiotic filipin III. The internalized ligands were present in particles corresponding to secondary endosomes in Percoll gradients, but especially in particles banding with the acid hexosaminidase lysosomal marker. At any temperature tested, internalization of the neuropeptide Y Y5 receptor driven by human neuropeptide Y in HEK-293 cells was much slower than the internalization of the neuropeptide Y Y1 receptor reported in the same cells, or in Chinese hamster ovary (CHO) cells. The neuropeptide Y Y5 receptor subtype could be the metabotropic receptor responding to protracted challenges by neuropeptide Y-like peptides, and its density could be little sensitive to concentration of extracellular agonists.


Early queen infection shapes developmental dynamics and induces long-term disease protection in incipient ant colonies.
Infections early in life can have enduring effects on an organism's development and immunity. In this study, we show that this equally applies to developing 'superorganisms'--incipient social insect colonies. When we exposed newly mated Lasius niger ant queens to a low pathogen dose, their colonies grew more slowly than controls before winter, but reached similar sizes afterwards. Independent of exposure, queen hibernation survival improved when the ratio of pupae to workers was small. Queens that reared fewer pupae before worker emergence exhibited lower pathogen levels, indicating that high brood rearing efforts interfere with the ability of the queen's immune system to suppress pathogen proliferation. Early-life queen pathogen exposure also improved the immunocompetence of her worker offspring, as demonstrated by challenging the workers to the same pathogen a year later. Transgenerational transfer of the queen's pathogen experience to her workforce can hence durably reduce the disease susceptibility of the whole superorganism.


Chemoradiotherapy versus triplet chemotherapy as initial therapy for T4b esophageal cancer: survival results from a multicenter randomized Phase 2 trial.
We report the long-term results as primary endpoint in a multicentre randomized prospective Phase 2 trial which compared chemoradiotherapy (CRT) and triplet chemotherapy (CT) as the initial therapy for conversion surgery (CS) in T4b esophageal cancer (EC). Patients with T4b EC were randomly assigned to the CRT group or CT group as initial treatment. CS was performed if resectable after initial or secondary treatment. The primary endpoint was 2-year overall survival, analysed by intention-to-treat. The median follow-up period was 43.8 months. The 2-year survival rate was higher in the CRT group (55.1%; 95% CI: 41.1-68.3%) compared to the CT group (34.7%; 95% CI: 22.8-48.9%), although the difference was not significant (P = 0.11). Local and regional lymph node recurrence in patients undergoing R0 resection was significantly higher in the CT group compared to the CRT group (local: 30% versus 8%, respectively, P = 0.03; regional: 37% versus 8%, respectively, P = 0.002). Upfront CT was not superior to upfront CRT as induction therapy for T4b EC in terms of 2-year survival and was significantly inferior to upfront CRT in terms of local and regional control. The Japan Registry of Clinical Trials (s051180164).


Sofosbuvir/velpatasvir/voxilaprevir: a highly effective option for retreatment of hepatitis C in difficult-to-treat patients.
Treatment for hepatitis C has escalated rapidly since the advent of direct-acting antivirals. Although there are highly efficacious, pangenotypic regimens available as standard of care, 5-10% of patients do not achieve virological cure. The recently approved fixed-dose combination of sofosbuvir, velpatasvir and voxilaprevir provides an option for retreatment in patients who have failed prior regimens and have characteristics which make them difficult to treat. This review provides a summary of the evidence for use of Vosevi®, a fixed-dose combination pill for treatment of hepatitis C in treatment-experienced patients.


The Protective Effects of Ramelteon Against Isoflurane-Induced Insults and Inflammatory Response in Brain Microvascular Endothelial Cells.
Anesthetic-induced cognitive impairment has been observed clinically. The mechanism underlying anesthetic-induced cognitive impairment is closely associated with neuronal apoptosis and neuroinflammation. Ramelteon is a potent and highly selective melatonin receptor agonist that has been used for the treatment of insomnia and has been reported to have an anti-inflammatory effect. In this study, we aimed to investigate the protective effects of Ramelteon against the cytotoxicity induced by isoflurane in brain microvascular endothelial cells. Our results show that Ramelteon ameliorated oxidative stress by suppressing the generation of mitochondrial reactive oxygen species (ROS) in human brain microvascular endothelial cells (HBMVECs). In addition, Ramelteon displayed a robust anti-inflammatory capacity against isoflurane-induced insults and inflammation by reducing the generation of interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), monocyte chemotactic protein 1 (MCP-1), stromal cell-derived factor-1 (SDF-1), matrix metalloproteinase-2 (MMP-2), and MMP-9. Furthermore, Ramelteon reduced the expression of cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Importantly, Ramelteon downregulated the activation of the p38MAPK/NF-κB signaling pathway, which is the key transcriptional regulator in the inflammation process. Our findings in the present study provide new evidence for the use of Ramelteon in the prevention of isoflurane-induced insults in brain endothelial cells.


Population-level quality indicators of end-of-life-care in an aged care setting: Rapid systematic review.
As their health declines, many older adults require additional care and move to residential aged care facilities. Despite efforts to reduce it, variation persists in care quality at the end-of-life (EOL) between facilities. Indicators to monitor care variation are therefore required. This rapid systematic review aims to identify population-level indicators of the quality of end-of-life-care (EOLC) for residents of aged care. A rapid systematic review of five databases (MEDLINE, Embase, CINAHL, PsycINFO, Scopus) for studies that reported on the development, assessment or validation of at least one measure of EOLC quality for residents living in an aged care setting from 1 January 2000 to 18 April 2023 was conducted. Abstracts and full-texts were screened by two reviewers and each indicator critically appraised. Key characteristics of each study were extracted. From seven studies, 106 EOLC quality indicators (75 of which were unique) for aged care residents were identified. Five studies specifically identified EOLC indicators for older residents with cognitive impairment. The EOLC quality indicators were diverse in nature. There were 31 EOLC quality indicators (22 unique indicators) focused on the structure and process of care provided and 51 (38 unique indicators) identified physical and psychological aspects of care. Twenty-three EOLC quality indicators (14 unique indicators) related to care of the imminently dying patient. A common suite of population-level EOLC indicators that are reflective of care quality, are clinically appropriate, and important to residents and their families should be identified to monitor EOLC quality within and across jurisdictions.


Long-term exposure to air pollution increases hip fracture incidence rate and related mortality: analysis of National Hip Fracture Database.
To explore the association of air pollution and hip fracture and related mortality in the UK. The average levels of PM2.5, PM10, and NO2 exhibited a positive association with hip fracture and short-term mortality while O3 did not. Our study highlights the association of air pollution and hip fracture. Until now, the influence of air pollution on bone mineral density and associated fractures has drawn little attention, and the consequences are controversial. To investigate the association between air pollution and hip fracture incidence and related short-term mortality. We constructed a cohort of all the National Hip Fracture Database beneficiaries (513,540 patients) in the UK from 2013 to 2018. Per year averages of PM2.5, PM10, O3, NO2, and SO2 were estimated according to the person's residence. The incidence rate ratio with 95% confidence interval and all-cause mortality within 30-day post-fracture (ACM30D) rate ratios were estimated using generalized additive models. The average levels of PM2.5, PM10, and NO2 exhibited a positive association with the incidence rate of hip fracture (IHF) and ACM30D. Whereas, this association was negative for O3 levels. Each increase of 5 μg per cubic meter in PM2.5, PM10, and NO2 leads to 9.5%, 9.2%, and 4.1% higher hip fracture rate, respectively, and also 9.3%, 8.3%, and 2.9% higher ACM30D, respectively. When we restricted the analysis to low-level exposure of air pollutants, similar results were obtained. Our study found a moderate, positive association between IHF, ACM30D, and the levels of specific air pollutants in the entire National Hip Fracture Database population. A reduction in the levels of PM2.5, PM10, and NO2 may decrease the hip fracture incidence rate and associated short-term mortality in older adults. Our study highlights the influence of air pollution on hip fracture.


A New Phenolate-Ion-Type Two-Photon Near Infrared Fluorophore-Based Biosensor for High-Performance Detection of HNO.
Although (E)-4-(2-(4-(dicyanomethylene)-4H-chromen-2-yl)vinyl)phenolate anion (DCPO- ) has recently emerged as a potential near infrared (NIR) biosensor signaling unit, the pKa value of its conjugate acid is relatively high (∼9); this will lead to relatively low concentrations of DCPO- under physiological conditions and, hence, unsatisfactory sensitivity of DCPO- -based bio-probes. By difluoro-substitution on DCPO- , we have exploited a new fluorophore of o-FDCPO- whose conjugate acid has a much lower pKa value of 7.42. Meanwhile, o-FDCPO- is NIR emissive with λem =693 nm and has a 0.76-fold higher fluorescence efficiency than DCPO- . The significant superiority of o-FDCPO- over DCPO- in sensitivity for NIR biosensor applications was confirmed by comparative studies on two HNO probes, namely o-FDCPO-P and DCPO-P, which bear signaling units of o-FDCPO- and DCPO- , respectively. Moreover, o-FDCPO-P has been demonstrated to be a high-performance HNO probe with high selectivity, high sensitivity (detection limit: 50 nm), and a rapid response, together with a two-photon NIR-excitation imaging capability.


CSF biomarkers in primary CNS lymphoma.
PCNSL is a non-Hodgkin lymphoma (NHL) affecting brain, spinal cord, eyes and leptomeninges. In the past two decades, its prognosis significantly improved due to therapeutic advances but it remains a highly aggressive tumor and early diagnosis is necessary for optimal management. Diagnosis relies on the identification of lymphoma cells in brain tissue obtained by stereotactic biopsy. Alternatively, lymphoma cells may be found in CSF through lumbar puncture (LP) or by a vitrectomy. For several reasons, the diagnosis of PCNSL may be challenging. Misleading radiological presentations are frequent. Dramatic response to steroids may bias histological analysis and deep brain location or frail health status can contraindicate brain biopsy. In the follow-up of patients who have been previously treated, differential diagnosis between tumor relapse and post-treatment may be also difficult. Therefore, the development of complementary reliable diagnostic tools is needed. This review will summarize several diagnostic or prognostic CSF biomarkers which have been proposed in PCNSL, their interests and limits.


Identification of shared antigenic determinants of different polypeptides from Davis and Towne cytomegalovirus strains with monoclonal antibodies.
Six colonies producing antibodies were obtained by fusing mouse myeloma SP2-O cells with spleen cells from mice immunized with cytomegalovirus Davis strain. Among 88 surviving clones, 29 produced antibodies detectable by immunofluorescence on infected MRC5 cells and 2 others produced neutralizing antibodies against a homologous virus. Supernatants from these 31 positive clones and 4 others which were negative in immunofluorescence or neutralization were tested for their capacity to bind polypeptides from labelled Davis-infected cell extracts. Only 8 were found to be positive: five clones (A8, E3, F2, F8 and F20) precipitated 76 K, 60 K and 54 K bands; three others (A4, B9 and C24) precipitated 76 K and 54 K only. Surprisingly, these 8 monoclonal antibodies recognized a unique polypeptide 67 K of Towne-infected MRC5 cells. No correlation was found between (1) the pattern of fluorescence on MRC5 cells infected with Davis strain, (2) the neutralizing activity, and (3) the polypeptides recognized by the monoclonal antibodies.


Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV.
Activity-regulated transcription has been implicated in adaptive plasticity in the CNS. In many instances, this plasticity depends upon the transcription factor CREB. Precisely how neuronal activity regulates CREB remains unclear. To address this issue, we examined the phosphorylation state of components of the CREB transcriptional pathway. We show that NMDA activates transcription of CREB-responsive genes in hippocampal neurons, with ERK responsible for persistent CREB phosphorylation and CaM kinase IV (CaMKIV) responsible for phosphorylating the CREB coactivator, CBP. Ser301 of CBP was identified as a major target of CaMKIV phosphorylation in vitro and in vivo. CaM kinase inhibitors attenuated phosphorylation at Ser301 and blocked CBP-dependent transcription. Additionally, mutation of Ser301 impaired NMDA- and CaMKIV-stimulated transcription. These findings demonstrate that activity-induced CaMKIV signaling contributes to CREB/CBP-dependent transcription by phosphorylating CBP at Ser301.


Insulin in the saliva of pigs: Validation of an automated assay and changes at different physiological conditions.
This study aimed to evaluate whether insulin could be measured in the saliva of pigs and if its concentration changes in some physiological conditions. For this purpose, a validation of an automated heterologous immunoassay for measuring insulin in the saliva of pigs was performed. In addition, the possible changes of salivary insulin concentration in sows after food intake and during gestation and lactation were studied. The evaluated immunoassay was able to detect insulin in the saliva of pigs in a precise and accurate way when species-specific calibrators were used. There was no correlation in insulin concentrations between serum and saliva. Insulin concentrations showed a significant increase in the saliva of sows after feeding. Sows at farrowing and lactation presented higher salivary insulin levels as compared with those in gestation. In conclusion, the results showed that insulin could be measured in the saliva of pigs, and changes in its concentration can be detected due to food intake and different physiological conditions.


Oculomotor nucleus afferents from the interstitial nucleus of Cajal and the region surrounding the fasciculus retroflexus in the rabbit.
After injecting horseradish peroxidase (HRP) or Fast blue in the oculomotor nucleus of the rabbit, two groups of labelled neurons were observed among the fibres of the rostral medial longitudinal fasciculus (MLF). The first group of neurons was located in the interstitial nucleus of Cajal (INC), mainly in the contralateral side to the injected oculomotor nucleus. The second group of labelled cells was located rostrally to the INC ipsilateral to the injection in the vicinity of the fasciculus retroflexus. These neurons might be homologous to those labelled in the INC and in the rostral interstitial nucleus of the MLF in frontal-eyed mammals, and involved in the control of vertical eye movements.


Acoustic Characterization of the Voice With a Tracheoesophageal Speech in Laryngectomized Patients. Similarities and Differences With the Laryngeal Voice.
Voice with tracheoesophageal speech (TES) is an effective, widely recognized option to restore the ability of oral communication to laryngectomized patients. In this study, we try to characterize the TES, taking account different variables and making an acoustic analysis of voice with TES versus laryngeal voice (LV). We compare different acoustic and subjective variables like GRABS or VHI in 34 patients with TES and 31 controls with LV. Patients with TES reach a good quality of voice with F0, F1, F2, F3, Jitter, Shimmer, and Yanahigara test similar to control group. Furthermore, the subjective scales show a good perception of voice for patients and examiners. Patients with tracheoesophageal voices show acceptable voice results, in many cases reaching to be near to controls with LV.


Celebrities and screening: a measurable impact on high-grade cervical neoplasia diagnosis from the 'Jade Goody effect' in the UK.
The celebrity Jade Goody's cervical cancer diagnosis was associated with increased UK cervical screening attendance. We wanted to establish if there was an increase in high-grade (HG) cervical neoplasia diagnoses, and if so, what the characteristics of the women with HG disease were. We analysed prospective data on 3233 consecutive colposcopy referrals in North East London, UK, from 01 April 2005 to 30 June 2010. Characteristics and outcomes of pre- and post-Goody cohorts were compared. Goody's diagnosis was associated with an increased incidence of colposcopy referrals in all subsequent annual quarters (incidence rate ratio (IRR) 1.3-1.9, P<0.002-P<0.0005) and increased HG disease diagnoses in the fourth quarter 2008/2009 (IRR 1.3, P=0.05) and first quarter 2009/2010 (IRR 1.3, P=0.07). We observed 1.90-fold (CI: 1.06-3.39), 2.06 (CI: 1.13-3.76) and 2.13-fold (CI: 1.07-4.25) respective increases in the odds of HG disease women being screening-naive in the first and second quarter 2009/2010, and the first quarter 2010/2011 (P<0.04, P<0.02 and P<0.04, respectively). There was a 2.23-fold increase in the odds of screening-naive HG disease women being symptomatic post-Goody's diagnosis (P=0.023). The age distributions of the pre- and post-Goody cohorts did not differ in any study group. Continued publicity about celebrities' diagnoses might encourage screening in at-risk populations.


Clinical perspectives on primary and secondary prevention of coronary atherosclerosis.
Several clinical trials have provided compelling evidence in support of the benefits of lipid-lowering therapy for primary and secondary prevention of atherosclerosis. The results of primary prevention trials have demonstrated that coronary morbidity can be reduced and survival improved with effective lipid-lowering regimens. There has been concern, however, regarding harmful effects (e.g., increased rate of suicide and increased risk of gastrointestinal cancer) of cholesterol-lowering therapies in primary prevention trials. These concerns are not well supported by strong evidence, and there has been lack of a dose-response relationship. It is generally believed that for 1% reduction in serum cholesterol, there is a 2% reduction in the risk of coronary events. The results of numerous secondary prevention trials have clearly demonstrated the benefit of lipid-lowering therapies in reducing the risk of future cardiac events and cardiac mortality in patients with preexistent coronary artery disease. Several studies have shown that treatment regimens effective in reducing LDL cholesterol levels lead to regression of atherosclerotic plaques as well as retard the progression of the disease process. Interestingly, some of these studies have also shown that when measured angiographically, the luminal diameter at the site of stenotic lesions might improve only by an average of 2% to 3%; however, this small degree of improvement is associated with a remarkable reduction by 35% to 25% in the risk of future coronary events. These findings further corroborate the hypothesis about the importance of a lipid-rich cap of the vulnerable plaques and suggest that the reduction in lipid levels is associated with the efflux of lipids from the plaque, thus converting it from a vulnerable to a stable state. The most recent data from the 4S trial have unequivocally demonstrated the benefits of treatment with HMG coenzyme-A reductase inhibitors in reducing the risk of future coronary events and improving the overall survival in patients with established CHD. Although there is still ongoing controversy regarding the precise course of action for primary prevention of CHD, the results of a large number of studies provide overwhelming evidence in support of aggressive lipid-lowering therapy for secondary prevention of CHD. Based on the findings of these studies, it seems prudent that clinicians become actively involved in the evaluation and management of lipid abnormalities and other risk factors in patients with CHD.


Adoptive transfer of xenoantigen‑stimulated T cell receptor Vβ‑restricted human regulatory T cells prevents porcine islet xenograft rejection in humanized mice.
Polyclonal expansion of human regulatory T cells (Tregs) prevents xenogeneic rejection by suppressing effector T cell responses in vitro and in vivo. However, a major limitation to using polyclonally expanded Tregs is that they may cause pan‑immunosuppressive effects. The present study was conducted to compare the ability of ex vivo expanded human xenoantigen‑stimulated Tregs (Xeno‑Treg) and polyclonal Tregs (Poly‑Treg) to protect islet xenografts from rejection in NOD‑SCID interleukin (IL)‑2 receptor (IL2r)γ‑/‑ mice. Human cluster of differentiation (CD)4+CD25+CD127lo Tregs, expanded either by stimulating with porcine peripheral blood mononuclear cells (PBMCs) or anti‑CD3/CD28 beads, were characterized by immune cell phenotyping, T cell receptor (TCR) Vβ CDR3 spectratyping and performing suppressive activity assays in vitro. The efficiency of adoptively transferred ex vivo human Tregs was evaluated in vivo using neonatal porcine islet cell clusters (NICC) transplanted into NOD‑SCID IL‑2rγ‑/‑ mice, which received human PBMCs with or without Xeno‑Treg or Poly‑Treg. Xeno‑Treg, which expressed increased levels of human leukocyte antigen‑DR and secreted higher levels of IL‑10, demonstrated enhanced suppressive capacity in a pig‑human mixed lymphocyte reaction. Spectratypes of TCR Vβ4, Vβ10, Vβ18 and Vβ20 in Xeno‑Treg showed restriction and expanded clones at sizes of 205, 441, 332 and 196 respectively, compared to those of Poly‑Treg. Reconstitution of mice with human PBMCs and Poly‑Treg resulted in NICC xenograft rejection at 63 days. Adoptive transfer with human PBMCs and Xeno‑Treg prolonged islet xenograft survival beyond 84 days, with grafts containing intact insulin‑secreting cells surrounded by a small number of human CD45+ cells. This study demonstrated that adoptive transfer of ex vivo expanded human Xeno‑Treg may potently prevent islet xenograft rejection in humanized NOD‑SCID IL2rγ‑/‑ mice compared with Poly‑Treg. These findings suggested that adoptive Treg therapy may be used for immunomodulation in islet xenotransplantation by minimizing systemic immunosuppression.


Hydrogen-bond induced enhanced emission ratiometric fluorescent handy needle for visualization assay of amoxicillin by smartphone sensing platform.
Amoxicillin (AMO) is one of the most commonly used antibiotics, and its abuse in animal husbandry or clinical therapy can pose unpredictable hazards to humans. Therefore, it is crucial to develop a real-time and rapid method to accurately determine AMO content. Here, we designed a fluorescent nanoprobe for qualitative and quantitative AMO determination by using as-synthesized green safe materials of nontoxic red carbon dots (RCDs) and blue carbon dots (BCDs). In the presence of AMO, a reaction promoting hydrogen bonding occurred immediately, resulting in an instant increase in the intensity of the blue fluorescence of BCDs, accompanied by a marked color change from red to blue. For practical application, we designed a nontoxic sensing fluorescent handy needle to directly and quantitatively detect AMO in real samples. This portable and easy-to-use device was demonstrated on a smartphone platform based on 3D printing technology, which offers the advantages of simple production, excellent visualization, fast response, and instant quantitative detection. The device requires an extremely short detection time and has a sensitive detection limit of 2.39 nM. The method presented here enables real-time assessment for food safety, as well as on-site detection under field conditions to track various trace substances for timely health checks.


Regulation of endogenous antigen presentation in response to suboptimal temperatures in a walleye skin fibroblast cell line.
A skin fibroblast cell line WE-skin11f from walleye (Sander vitreus) was used to study the impact of temperature (26 °C, 20 °C, 14 °C, or 4 °C) on the transcript levels of genes involved in the endogenous antigen processing and presentation pathway (EAPP), which is an important antiviral pathway of vertebrates. Partial coding sequences were found for 4 previously unidentified walleye EAPP members, calreticulin, calnexin, erp57, and tapasin, and the constitutive transcript levels of these genes in WE-skin11f was unchanged by culture incubation temperature. The viral mimic poly (I:C) and viral haemorrhagic septicaemia virus (VHSV) IVb were used to study possible induction of EAPP transcripts (b2m, mhIa, and tapasin). The walleye cells were exquisitely sensitive to poly (I:C), losing adherence and viability at concentrations greater than 100 ng/mL, particularly at suboptimal temperatures. VHSV IVb viral particles were produced from infected WE-skin11f cells at 20 °C, 14 °C, and 4 °C but with much lower production at 4 °C. Under conditions where their impact on the viability of WE-skin11f cultures was slight, poly (I:C) and VHSV IVb were shown to induce b2m, mhIa, and tapasin transcript°s at 26 °C and 20 °C respectively. However, at 4 °C, the up-regulation of EAPP transcript levels was either delayed or completely impaired when compared to the 26 °C and 20 °C control temperatures of the respective experiments. These in vitro results suggest that suboptimal temperatures may be capable of modulating the regulation of the EAPP in walleye cells during viral infection.


Molecular mechanisms of copper metabolism and the role of the Menkes disease protein.
Menkes disease is an X-linked, recessive disorder of copper metabolism that occurs in approximately 1 in 200,000 live births. The condition is characterized by skeletal abnormalities, severe mental retardation, neurologic degeneration, and patient mortality in early childhood. The symptoms of Menkes disease result from a deficiency of serum copper and copper-dependent enzymes. A candidate gene for the disease has been isolated and designated MNK. The MNK gene codes for a P-type cation transporting ATPase, based on homology to known P-type ATPases and in vitro experimentation. cDNA clones of MNK in Menkes patients show diminished or absented hybridization in northern blot experiments. The Menkes protein functions to export excess intracellular copper and activates upon Cu(I) binding to the six metal-binding repeats in the amino-terminal domain. The loss of Menkes protein activity blocks the export of dietary copper from the gastrointestinal tract and causes the copper deficiency associated with Menkes disease. Each of the Menkes protein amino-terminal repeats contains a conserved -X-Met-X-Cys-X-X-Cys- motif (where X is any amino acid). These metal-binding repeats are conserved in other cation exporting ATPases involved in metal metabolism and in proteins involved in cellular defense against heavy metals in both prokaryotes and eukaryotes. An overview of copper metabolism in humans and a discussion of our understanding of the molecular basis of cellular copper homeostasis is presented. This forms the basis for a discussion of Menkes disease and the protein deficit in this disease.


Augmentation cystoplasty: what are the indications?
Augmentation cystoplasty has been studied and performed by urologists for more than 100 years. Although specific indications, techniques, and materials used have undergone major changes and revisions during this period, the general concepts have remained the same. Bladder augmentation increases the bladder's storage capacity. Specific indications include structurally diminished bladder capacity, neurogenically incapacitated bladder, special circumstances of overactive bladder, and interstitial cystitis. This article briefly reviews techniques including laparoscopic and extraperitoneal approaches. Most common long-term consequences of bladder augmentation including chronic infections, bladder stones, perforation, and malignancy are described. Overall, we demonstrate that in appropriately selected patients, bladder augmentation presents an excellent treatment option to improve bladder capacity, achieve socially acceptable continence, and stabilize renal function.


Oxygen-enriched air for co-incineration of organic sludges with municipal solid waste: a pilot plant experiment.
Pilot-plant experiments were performed to evaluate the effect of oxygen enrichment on the co-incineration of MSW and organic sludge from a wastewater treatment facility. Combustion chamber temperatures, stack gas concentrations, i.e., CO(2) and CO, and the residual oxygen were measured. The maximum ratio of organic sludge waste to total waste input was 30 wt.%. Oxygen-enriched air, 22 vol.% (dry basis) oxygen, was used for stable combustion. As the co-incineration ratio of the sludge increased, the primary and secondary combustion chamber temperatures were decreased to 900 and 750 degrees C, respectively, approximately 100 degrees C below the proper incineration. However, if the supplied air was enriched with 22 vol.% (dry basis) oxygen content, the incinerator temperature was high enough to burn the waste mixture containing 30 wt.% moisture sludge, with an estimated heating value of 6.72 MJ/kg. There are two main benefits of using oxygen enrichment in the co-incineration. First, the sensible heat can be reduced as the quantity of nitrogen in the flue gas will be decreased. Second, the unburned carbon formation is reduced due to the oxygen-enriched burning of the waste, despite an increase in the sludge co-incineration ratio.