The reliability of performing a screening cystometrogram using a fetal monitoring device for the detection of detrusor instability.
To determine if a cystometrogram performed using the intrauterine pressure channel of a fetal monitor can be used to screen for detrusor instability in women undergoing evaluation for urinary incontinence. Sixty-six women with primary complaints of urinary incontinence were randomized to have a cystometrogram performed at their initial visit with a multichannel electronic cystometer or with the intrauterine pressure channel of a fetal monitor. Subjects underwent a second cystometrogram 1-4 weeks later with the alternative technique. The results were analyzed with chi 2 analysis and correlation coefficients. Twenty-two subjects had detrusor instability diagnosed by the multichannel electronic cystometer. The fetal monitor cystometrogram was 91% sensitive and 86% specific in detecting detrusor instability, and had a 77% positive predictive value and a 95% negative predictive value. The correlation coefficients between the two examinations for bladder volume at first sensation, maximum capacity, volume at first contraction, and intensity of uninhibited detrusor contraction were r = 0.51, r = 0.69, r = 0.87, and r = 0.79, respectively; all of these were statistically significant. The intrauterine pressure channel of a fetal monitor can be used reliably to perform a cystometrogram to screen for detrusor instability in patients presenting with complaints of urinary incontinence.


Gene therapy for lipoprotein lipase deficiency.
The present review summarizes the clinical development of adeno-associated viral vector (AAV)1-lipoprotein lipase (LPL)S447X gene therapy (alipogene tiparvovec) for lipoprotein lipase deficiency. Lipoprotein lipase deficiency is a rare inherited disease characterized by severe hypertriglyceridaemia, chylomicronaemia and risk of recurrent pancreatitis or other complications. AAV1-LPLS447X gene therapy is based on the rationale that by adding episomal copies of functional LPL genes into muscle cells lacking active LPL, metabolic function could be improved or restored. AAV1-LPLS447X is a nonreplicating and nonintegrating AAV of serotype 1 designed to deliver and express the human LPL gene variant S447X. The clinical development programme for AAV1-LPLS447X consisted of two observational studies, three open-label interventional studies and one case note review analysis. Intramuscular administration of AAV1-LPLS447X was generally well tolerated and was associated with reduction in overall pancreatitis incidence and signs of clinical improvement up to 2 years after administration. Results of interventional studies suggest that markers of postprandial metabolism could be more accurate than fasting plasma triglyceride concentration to monitor the effect of AAV1-LPLS447X . The overall benefit-risk ratio of AAV1-LPLS447X gene therapy appears positive to date, particularly for the patients presenting the highest risk of complications.


Reviewing the research process for postanesthesia care unit studies.
Research studies are needed by and for nurses to validate nursing practice. PACU nurses are in an excellent position to validate PACU nursing practice through research studies that seek solutions to patient problems. Research ideas also may be derived from formal and informal discussions at professional meetings, by testing new products, and reviewing the literature; however, precise steps must be followed to assure accuracy of data collection and the interpretation of the results.


Ocular pharmacokinetics of a single dose of bromfenac sodium ophthalmic solution 0.1% in human aqueous humor.
The aim of this study was to evaluate the ocular pharmacokinetics of a single dose of bromfenac sodium ophthalmic solution 0.1% in subjects undergoing routine cataract surgery with intraocular lens implantation. An open-label, phase II confirmatory study of 54 subjects undergoing cataract surgery with intraocular lens implantation. A single drop of bromfenac sodium ophthalmic solution 0.1% was administered at 30, 60, 90, 120, 180, or 240 min prior to the initiation of cataract surgery. Samples of aqueous humor were aspirated through a paracentesis and analyzed by using high-performance liquid chromatography. Based upon these data, predicted concentrations of bromfenac in the aqueous humor over 24 h were generated by using computer simulation and compared with the IC(50) for bromfenac as a measure of anti-inflammatory efficacy. Peak aqueous-humor concentrations of bromfenac occurred between 150 and 180 min following ophthalmic dosing, with a mean concentration of 78.7 ng/mL. The level of bromfenac decreased in a log-linear fashion with an elimination-rate constant of 1.4. Bromfenac remained above the IC(50) value of cyclo-oxygenase-2 (COX-2) during the evaluated time points and over the 12-h dosing interval, using a computer model of extrapolated time points and assuming first-order elimination. Pharmacokinetic modeling, based upon samples collected over 240 min after a single dose of bromfenac sodium ophthalmic solution 0.1% suggests that aqueous-humor concentrations remain at clinically effective levels (above its IC(50) value for COX-2) for over 12 h. Based upon this rationale, these results supported clinical trials that demonstrated the efficacy of twice-daily dosing of bromfenac sodium ophthalmic solution 0.1% to manage patients with postoperative ocular pain and inflammation.


The saprotrophic Pleurotus ostreatus species complex: late Eocene origin in East Asia, multiple dispersal, and complex speciation.
The Pleurotus ostreatus species complex is saprotrophic and of significant economic and ecological importance. However, species delimitation has long been problematic because of phenotypic plasticity and morphological stasis. In addition, the evolutionary history is poorly understood due to limited sampling and insufficient gene fragments employed for phylogenetic analyses. Comprehensive sampling from Asia, Europe, North and South America and Africa was used to run phylogenetic analyses of the P. ostreatus species complex based on 40 nuclear single-copy orthologous genes using maximum likelihood and Bayesian inference analyses. Here, we present a robust phylogeny of the P. ostreatus species complex, fully resolved from the deepest nodes to species level. The P. ostreatus species complex was strongly supported as monophyletic, and 20 phylogenetic species were recognized, with seven putatively new species. Data from our molecular clock analyses suggested that divergence of the genus Pleurotus probably occurred in the late Jurassic, while the most recent common ancestor of the P. ostreatus species complex diversified about 39 Ma in East Asia. Species of the P. ostreatus complex might migrate from the East Asia into North America across the North Atlantic Land Bridge or the Bering Land Bridge at different times during the late Oligocene, late Miocene and late Pliocene, and then diversified in the Old and New Worlds simultaneously through multiple dispersal and vicariance events. The dispersal from East Asia to South America in the middle Oligocene was probably achieved by a long-distance dispersal event. Intensification of aridity and climate cooling events in the late Miocene and Quaternary glacial cycling probably had a significant influence on diversification patterns of the complex. The disjunctions among East Asia, Europe, North America and Africa within Clade IIc are hypothesized to be a result of allopatric speciation. Substrate transitions to Apiaceae probably occurred no earlier than 6 Ma. Biogeographic analyses suggested that the global cooling of the late Eocene, intensification of aridity caused by rapid uplift of the QTP and retreat of the Tethys Sea in the late Miocene, climate cooling events in Quaternary glacial cycling, and substrate transitions have contributed jointly to diversification of the species complex.


The role of gamma-aminobutyric acid/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons.
Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)/glycine switches from excitatory to inhibitory during development in the ventral cochlear nucleus (VCN), one of the most sensitive auditory nuclei to bilirubin toxicity. In the present study, we investigated the roles of GABAA/glycine receptors in the induction of bilirubin hyperexcitation in early developing neurons. Using the patch clamp technique, GABAA/glycine receptor-mediated spontaneous inhibitory synaptic currents (sIPSCs) were recorded from bushy and stellate cells in acute brainstem slices from young mice (postnatal day 2-6). Bilirubin significantly increased the frequency of sIPSCs, and this effect was prevented by pretreatments of slices with either fast or slow Ca(2+) chelators BAPTA-AM and EGTA-AM suggesting that bilirubin can increase the release of GABA/glycine via Ca(2+)-dependent mechanisms. Using cell-attached recording configuration, we found that antagonists of GABAA and glycine receptors strongly attenuated spontaneous spiking firings in P2-6 neurons but produced opposite effect in P15-19 neurons. Furthermore, these antagonists reversed bilirubin-evoked hyperexcitability in P2-6 neurons, indicating that excitatory action of GABA/glycinergic transmission specifically contribute to bilirubin-induced hyperexcitability in the early stage of development. Our results suggest that bilirubin-induced enhancement of presynaptic release GABA/Glycine via Ca(2+)-dependent mechanisms may play a critical role in mediating neuronal hyperexcitation associated with jaundice, implicating potential new strategies for predicting, preventing, and treating bilirubin neurotoxicity.


Identifying environmental factors that influence the outcomes of people with traumatic brain injury.
To determine the types of environmental barriers reported by persons with traumatic brain injury (TBI) and to identify the relations between environmental barriers and such components of societal participation as employment, community mobility, social integration, and life satisfaction. Seventy-three persons with TBI who were participating in the TBI Model Systems program at Craig Hospital were surveyed at 1 year, using a new measure of the environment, the Craig Hospital Inventory of Environmental Factors (CHIEF), which rates frequency and impact of 25 barriers. Transportation, the surroundings, government policies, attitudes, and the natural environment were the environmental barriers with the greatest reported impact. Those who were married, older, and unemployed or not in school reported the most barriers overall. Additionally, those reporting a greater impact from environmental barriers also reported lower levels of participation and life satisfaction. Although environmental barriers affect TBI survivors and play a role in their outcomes, their interplay with other, perhaps as yet unidentified, factors requires continued research. CHIEF may be a valuable tool for understanding the environment's role in the lives of people with TBI, and identifying the general environmental domains where interventions are needed to reduce their negative impact.


Peripheral inflammation is associated with brain SPECT perfusion changes in schizophrenia.
Peripheral inflammation is frequent in schizophrenia and could play a role in the pathophysiology, prognosis, and persistence of psychotic symptomatology under treatment. We seek to determine the relationship between peripheral inflammation and brain SPECT perfusion in stabilized antipsychotic-treated outpatients with schizophrenia, and to determine whether such perfusion changes are correlated with persistent symptoms. Highly sensitive C-reactive protein blood level (hs-CRP) and brain SPECT perfusion were assessed in 137 stabilized outpatients with schizophrenia. Whole-brain voxel-based associations were searched with SPM between SPECT perfusion and hs-CRP (correlation analysis to quantitative levels and between-group analysis according to a threshold of 3 mg/L). The identified clusters were secondarily correlated with clinical symptoms. After adjustment for age, sex, educational level, illness duration, antidepressant use, chlorpromazine equivalent dose, tobacco smoking and obesity, a negative correlation was found between hs-CRP level and the perfusion of 4 brain areas: the right inferior frontal gyrus, the right middle/superior temporal gyrus, the left superior parietal lobe, and the right postcentral/transverse temporal gyrus (p-voxel < 0.001, k > 80, uncorrected). Increased perfusion of the left amygdala was found in patients with hs-CRP ≥ 3 mg/L compared to those with hs-CRP levels < 3 mg/L. A negative correlation was found between perfusion of the right inferior frontal gyrus and the persistence of positive, negative, and excitement symptoms under antipsychotic treatment. In stabilized patients with schizophrenia, peripheral inflammation is associated with brain perfusion changes that are correlated with the persistence of psychotic symptomatology.


Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis.
Increases in lumbar spine BMD account for 30-41% of the vertebral fracture risk reduction with teriparatide treatment. The remaining fracture risk reduction is caused by improvements in non-BMD determinants of bone strength. Changes in BMD account for a small percentage of the fracture risk reduction seen in patients treated with antiresorptive drugs. The relationship between changes in lumbar spine BMD and vertebral fracture risk reduction with teriparatide treatment has not been assessed. The relationship between spine BMD and the risk of new vertebral fractures after teriparatide treatment was assessed using data from the Fracture Prevention Trial. Postmenopausal women with osteoporosis (n = 1637) were randomized to placebo or teriparatide 20 or 40 microg/day for a median of 19 months. Spine BMD was assessed at baseline and 18 months. Vertebrae whose fracture status changed during the trial were removed from the calculation of BMD. Baseline and endpoint lateral spine radiographs were assessed using a visual semiquantitative technique. Both the baseline and change in spine BMD were contributors to vertebral fracture risk. The mean spine BMD increase in teriparatide-treated patients was 0.09 g/cm(2) across tertiles of baseline spine BMD. Compared with placebo, teriparatide significantly reduced the risk of new vertebral fracture for all endpoint BMD values. Teriparatide-mediated increases in spine BMD accounted for 30% (in the low baseline spine BMD tertile) to 41% (in the high baseline spine BMD tertile) of the reduction in vertebral fracture risk. Increases in BMD account for approximately one third of the vertebral fracture risk reduction seen with teriparatide. The majority of the risk reduction, however, results from improvements in non-BMD determinants of bone strength.


Deep mantle structure and the postperovskite phase transition.
Seismologists have known for many years that the lowermost mantle of the Earth is complex. Models based on observed seismic phases sampling this region include relatively sharp horizontal discontinuities with strong zones of anisotropy, nearly vertical contrasts in structure, and small pockets of ultralow velocity zones (ULVZs). This diversity of structures is beginning to be understood in terms of geodynamics and mineral physics, with dense partial melts causing the ULVZs and a postperovskite solid-solid phase transition producing regional layering, with the possibility of large-scale variations in chemistry. This strong heterogeneity has significant implications on heat transport out of core, the evolution of the magnetic field, and magnetic field polarity reversals.


Antifibrotic effect of pirfenidone on human pterygium fibroblasts.
The effects of pirfenidone were investigated on cultured human pterygium fibroblasts (HPFs). HPFs were obtained from pterygium surgery and subjected to primary culture. After treatment with 0.5, 1.0 or 1.5 mg/mL pirfenidone, MTT and cell migration assays were performed, and procollagen secretion and TGF-β expression were measured by Western blotting and immunofluorescence analysis. Pirfenidone had a significant inhibitory effect on HPF proliferation, migration and collagen synthesis. There were no differences between the cells treated with 0.5, 1.0 and 1.5 mg/mL pirfenidone and the controls in the MTT assay. After 48 h of treatment with 1.0 or 1.5 mg/mL pirfenidone, TGF-β expression was significantly decreased. These findings demonstrate that pirfenidone inhibits the proliferation, migration and procollagen secretion of HPFs at nontoxic concentrations by decreasing TGF-β expression. Thus, pirfenidone may be considered as a safe adjuvant for pterygium surgery to prevent recurrence.


Association between NDO-LID and PGL-1 for leprosy and class I and II human leukocyte antigen alleles in an indigenous community in Southwest Amazon.
The frequencies of the Human leukocyte antigen (HLA) alleles in the Puyanawa indigenous reserve population and their association with the NDO-LID and ELISA PGL-1 rapid serological test was assessed. This was a cross-sectional study with an epidemiological clinical design conducted in two indigenous communities in the state of Acre, Brazil. Blood was collected in a tube with EDTA to identify HLA alleles and perform serological tests. DNA was obtained using the salting out procedure. The LabType™ technique (One-Lambda-USA) was used for HLA class I (loci A*, B* and C*) and II (loci DRB1*, DQA1* and DQB1*) typing. Allele frequency was obtained by direct count, and the chi-square test was used to assess the association with the NDO-LID and PGL-1 tests. The most frequent alleles in the two communities were: HLA-A*02:01, HLA-B*40:02, HLA-DRB1*16:02, HLA-DQA1*05:05 and HLA-DQB1*03:01. The allele HLA-C*04:01 was the most common in the Barão community, and the allele HLA-C*07:01 in Ipiranga. Among individuals who presented seropositivity to the NDO-LID test, the association with alleles HLA-A*02 (43.18% vs 24.8%, p=0.03, OR=2.35) and HLA-B*53 (6.83% vs 0.0%, p=0.03, OR=8.95) was observed in the Barão community. HLA-B*15 was associated with non-seroconversion to the NDO-LID test in Ipiranga. In both communities, HLA-B*40 and HLA-C*03 were associated with positive serological response to ELISA PGL-1. The HLA class I and II alleles most frequently found in this study have already been described among Terena indigenous groups, and HLA class I contributes to seroconversion to NDO-LID and PGL-1 tests in inhabitants of the Barão and Ipiranga communities.


Cell polarization and cytokinesis in budding yeast.
Asymmetric cell division, which includes cell polarization and cytokinesis, is essential for generating cell diversity during development. The budding yeast Saccharomyces cerevisiae reproduces by asymmetric cell division, and has thus served as an attractive model for unraveling the general principles of eukaryotic cell polarization and cytokinesis. Polarity development requires G-protein signaling, cytoskeletal polarization, and exocytosis, whereas cytokinesis requires concerted actions of a contractile actomyosin ring and targeted membrane deposition. In this chapter, we discuss the mechanics and spatial control of polarity development and cytokinesis, emphasizing the key concepts, mechanisms, and emerging questions in the field.


A gigantic anogenital lesion: buschke-lowenstein tumor.
Buschke-Lowenstein tumor is a relatively rare sexually transmitted disease. It is a neoplasm of the anogenital region which has benign appearance on histopathology but is locally destructive. It carries a high recurrence rate and a significant potential for malignant transformation. Human papilloma virus has been implicated as an etiologic agent for this tumor. Since this disease is rare and no controlled studies exist, radical excision of this anogenital lesion is generally recommended as the first line therapy and close vigilance and followup are essential. We have discussed an overview of etiopathogenesis, clinical presentation, diagnosis, and management of this uncommonly encountered disease.


[Prostatotomy. Long-term results].
Sixty-five patients were treated with transurethral incision of the prostate (TUI-P) on account of slight obstructive enlargement of the prostate. Out of these, 46 were followed-up with a median period of observation of just under four years. In five patients prostatotomy proved insufficient and resection or repeated TUI-P was necessary. 80% of the patients considered that micturition had improved as assessed subjectively by means of a simple rank scale. Assessed symptomatically according to Madsen & Iversen's scale, a median score of 2 and less than 10 was found in 85%. Assessed objectively by means of urine flow measurement, a median peak flow of 10.5 ml/second was found and greater than 9 ml/second in 73%. No structures were demonstrated and none of the patients were incontinent. The magnitude of the ejaculate was unchanged in 26%, less in 39% while this was unknown in 35%. These results do not differ essentially from corresponding long term observations and the method must be considered particularly suitable for treatment of obstructive moderate hypertrophy of the prostate.


A multi-wavelength, high-contrast contact radiography system for the study of low-density aerogel foams.
A multi-wavelength, high contrast contact radiography system has been developed to characterize density variations in ultra-low density aerogel foams. These foams are used to generate a ramped pressure drive in materials strength experiments at the National Ignition Facility and require precision characterization in order to reduce errors in measurements. The system was used to characterize density variations in carbon and silicon based aerogels to ∼10.3% accuracy with ∼30 μm spatial resolution. The system description, performance, and measurement results collected using a 17.8 mg/cc carbon based JX-6 (C20H30) aerogel are discussed in this manuscript.


Differential control of the hyperpolarization-activated current (i(f)) by cAMP gating and phosphatase inhibition in rabbit sino-atrial node myocytes.
1. The actions of the phosphatase inhibitor calyculin A on the hyperpolarization-activated cardiac 'pacemaker' current (i(f)) were determined in single cells isolated from the sino-atrial (SA) node of the rabbit. 2. Cells were incubated for 8 min in Tyrode solution containing calyculin A (0.5 microM) and then superfused with normal Tyrode solution. The mean normalized i(f) measured in eight cells at mid-activation voltages during and after exposure to calyculin A increased maximally by 47% with a time constant of 466 s, a time much longer than that required for cAMP-mediated i(f) stimulation (about 8 s). 3. In two-pulse protocols, calyculin A treatment increased i(f) at full as well as at mid-activation voltages, indicating a higher i(f) conductance. 4. Measurement of the conductance-voltage (gf(V)) relation by voltage ramp protocols confirmed a conductance increase by calyculin A, with no significant change in the position of the activation curve on the voltage axis. Data pooled together from ramp and two-pulse protocols yielded a calyculin A-induced increase in fully activated i(f) conductance of 39.6 +/- 6.4% (n = 16 cells). 5. The positive and negative shift of i(f) voltage dependence in response to beta-adrenergic (1 microM isoprenaline) and muscarinic stimulation (1 microM acetylcholine), respectively, was preserved after the calyculin A-induced increase in conductance. The shift of the i(f) activation curve induced by 1 microM isoprenaline was significantly larger in calyculin A-treated cells (8.8 vs. 5.8 mV). 6. These data indicate that phosphatase inhibition increases i(f) in a manner distinct from the direct cAMP pathway and potentiates the beta-adrenergic-mediated i(f) modulation.


Risks for cervical intraepithelial neoplasia 3 among adolescents and young women with abnormal cytology.
To estimate the risks of cervical intraepithelial neoplasia (CIN) 3 among girls and women aged 13 to 24 years who were referred for abnormal cytology while receiving care in a large health maintenance organization. At the time of referral, patients had a colposcopic examination and biopsy if needed. Histology was sent to a centralized laboratory. Patients were interviewed for risk behaviors. Data analysis included multinomial logistic regression analysis to compare three groups: CIN 3 to CIN 1 or less, CIN 3 to CIN 2, and CIN 2 to CIN 1 or benign. Cervical intraepithelial neoplasia-3 was found in 6.6% (95% confidence interval [CI] 4.6-8.6%) of the 622 girls and women referred and no cancers were detected. Risk for CIN 3 compared to CIN 1 or less included human papillomavirus 16 or 18 (odds ratio [OR] 30.93, 95% CI 6.95-137.65), high-risk, non-16/18 human papillomavirus (OR 6.3, 95% CI 1.3-29.4), and time on oral contraceptives (OR 1.36 per year of use, 95% CI 1.08-1.71). Our data support conservative care for adolescents and young women with abnormal cytology since CIN 3 was rare and cervical cancer was never found. Human papillomavirus 16 or 18 was strongly associated with for CIN 3, and testing for these types may be warranted for triage of abnormal cytology in this age group. II.


Functional cell-surface display of a lipase-specific chaperone.
Lipases are important enzymes in biotechnology. Extracellular bacterial lipases from Pseudomonads and related species require the assistance of specific chaperones, designated "Lif" proteins (lipase specific foldases). Lifs, a unique family of steric chaperones, are anchored to the periplasmic side of the inner membrane where they convert lipases into their active conformation. We have previously shown that the autotransporter protein EstA from P. aeruginosa can be used to direct a variety of proteins to the cell surface of Escherichia coli. Here we demonstrate for the first time the functional cell-surface display of the Lif chaperone and FACS (fluorescence-activated cell sorting)-based analysis of bacterial cells that carried foldase-lipase complexes. The model Lif protein, LipH from P. aeruginosa, was displayed at the surface of E. coli cells. Surface exposed LipH was functional and efficiently refolded chemically denatured lipase. The foldase autodisplay system reported here can be used for a variety of applications including the ultrahigh-throughput screening of large libraries of foldase variants generated by directed evolution.


Reactivity studies of 3,3-bis(trimethylsilyl)-2-methyl-1-propene in Lewis acid-catalyzed allylation reactions.
Allylation reagents, which possess geminal bis-trimethylsilyl substitution, are readily prepared from E- or Z-alkenyl bromides. The reactivity of 3,3-bis(trimethylsilyl)-2-methyl-1-propene (1) is described and predominantly provides ene reactions with aldehydes to give alcohol 2 in the presence of BF3.OEt2. Alternatively, Sakurai allylation reactions of 1 are observed by using stronger Lewis acids in methylene chloride to exclusively yield E-trisubstituted alkenylsilanes 3.


An Investigation of the Altered Textural Property in Woody Breast Myopathy Using an Integrative Omics Approach.
Woody breast (WB) is a myopathy observed in broiler Pectoralis major (PM) characterized by its tough and rubbery texture with greater level of calcium content. The objective of this study was to investigate the functionality/integrity of WB sarcoplasmic reticulum (SR), which may contribute to the elevated calcium content observed in WB and other factors that may influence WB texture. Fourteen Ross line broiler PM [7 severe WB and 7 normal (N)] were selected, packaged, and frozen at -20°C at 8 h postmortem from a commercial processing plant. Samples were used to measure pH, sarcomere length, proteolysis, calpain activity, collagenase activity, collagen content, collagen crosslinks density, and connective tissue peak transitional temperature. Exudate was also collected from each sample to evaluate free calcium concentration. The SR fraction of the samples was separated and utilized for proteomic and lipidomic analysis. The WB PM had a higher pH, shorter sarcomeres, lower % of intact troponin-T, more autolyzed μ/m calpain, more activated collagenase, greater collagen content, greater mature collagen crosslinks density, and higher connective tissue peak transitional temperature than the N PM (p ≤ 0.05). Exudate from WB PM had higher levels of free calcium than those from N PM (p < 0.05). Proteomics data revealed an upregulation of calcium transport proteins and a downregulation of proteins responsible for calcium release (p < 0.05) in WB SR. Interestingly, there was an upregulation of phospholipase A2 (PLA2), and cholinesterase exhibited a 7.6-fold increase in WB SR (p < 0.01). Lipidomics data revealed WB SR had less relative % of phosphatidylcholine (PC) and more lysophosphatidylcholine (LPC; p < 0.05). The results indicated that upregulation of calcium transport proteins and downregulation of calcium-release proteins in WB SR may be the muscle's attempt to regulate this proposed excessive signaling of calcium release due to multiple factors, such as upregulation of PLA2 resulting in PC hydrolysis and presence of cholinesterase inhibitors in the system prolonging action potential. In addition, the textural abnormality of WB may be the combined effects of shorter sarcomere length and more collagen with greater crosslink density being deposited in the broiler PM.


Quantitation of xanthurenic acid in rabbit serum using high performance liquid chromatography.
Xanthurenic acid (XA) has been quantified in the serum of normal and vitamin B6-deficient rabbits using high performance liquid chromatography. The concentration of XA in the serum of normal and B6-deficient rabbits was 141 and 2275 ng/ml, respectively. The coefficient of variation for a series of dilutions of standard XA (3.9 to 1000 ng) ranged from 45.5% at the lower limit of the curve to 10.9% at the higher range of the curve. The minimum detectable level was 3.9 ng/ml. Serum samples spiked with reference XA exhibited a parallel dose response. The percentage recovery of XA from serum samples was 80.8%. The procedure, which requires 1 to 2 ml of serum, is sensitive and may be a useful tool for assessing B6 nutritional parameters as well as the physiological role of XA. It offers advantages over urinary procedures because it is more sensitive, more specific, and allows the study of blood levels of XA.


Fenofibrate inhibits endothelin-1 expression by peroxisome proliferator-activated receptor α-dependent and independent mechanisms in human endothelial cells.
Dyslipidemia contributes to endothelial dysfunction in type 2 diabetes mellitus. Fenofibrate (FF), a ligand of the peroxisome proliferator-activated receptor-α (PPARα), has beneficial effects on microvascular complications. FF may act on the endothelium by regulating vasoactive factors, including endothelin-1 (ET-1). In vitro, FF decreases ET-1 expression in human microvascular endothelial cells. We investigated the molecular mechanisms involved in the effect of FF treatment on plasma levels of ET-1 in type 2 diabetes mellitus patients. FF impaired the capacity of transforming growth factor-β to induce ET-1 gene expression. PPARα activation by FF increased expression of the transcriptional repressor Krüppel-like factor 11 and its binding to the ET-1 gene promoter. Knockdown of Krüppel-like factor 11 expression potentiated basal and transforming growth factor-β-stimulated ET-1 expression, suggesting that Krüppel-like factor 11 downregulates ET-1 expression. FF, in a PPARα-independent manner, and insulin enhanced glycogen synthase kinase-3β phosphorylation thus reducing glycogen synthase kinase-3 activity that contributes to the FF-mediated reduction of ET-1 gene expression. In type 2 diabetes mellitus, improvement of flow-mediated dilatation of the brachial artery by FF was associated with a decrease in plasma ET-1. FF decreases ET-1 expression by a PPARα-dependent mechanism, via transcriptional induction of the Krüppel-like factor 11 repressor and by PPARα-independent actions via inhibition of glycogen synthase kinase-3 activity.


Portable Face-Shielding Device Based on sEMG Considering the COVID-19 Scenario.
Wearing a mask greatly reduced the possibility of infection during the COVID-19 pandemic. However, major inconveniences occur regarding patients with upper limb amputations, as they cannot independently wear masks. As a result, bacterial contamination is caused by medical staff touching the quilt when helping. Furthermore, this effect can occur with ordinary people due to accidental touch. This research aims to design an automatic and portable face shield assistive device based on surface electromyography (sEMG) signals. A concise face shield-wearing mechanism was built through 3D printing. A novel decision-making control method regarding a feature extraction model of 16 signal features and a Softmax classification neural network model were developed and tested on an STM32 microcontroller unit (MCU). The optimized electrode was fabricated using a carbon nanotube (CNT)/polydimethylsiloxane (PDMS). The design was further integrated and tested, showing a promising future for further implementation.


The causes and treatments of phantom limb pain.
Almost all patients who undergo amputation suffer 'phantom sensations', a sensory perception of the missing limb, possibly caused by a neural imprint or memory of the limb within the brain. The patient may experience abnormal kinaesthetic sensation, such as the feeling that the limb is in an abnormal position. Perceived changes in length, size or temperature of the limb are also common. Some of these people will go on to develop phantom limb pain (PLP). Appropriate aggressive pain management is required immediately postamputation in an attempt to avoid chronic PLP.


Emergency appendicectomy in Australia: findings from a multicentre, prospective study.
Emergency appendicectomy is the most common emergency surgical procedure performed in Australia. Despite this frequency, there is a relative paucity of contemporary, broad-based, local data that examine how emergency appendicectomies are currently performed and what are the outcomes from these operations. A multicentre, prospective, observational study was performed. Patients were recruited by local investigators for a period of 2 months with 30-day follow-up. Patients were eligible for study inclusion if they underwent an emergency appendicectomy for suspected acute appendicitis. The primary outcome of the study was the negative appendicectomy rate (NAR), with secondary outcomes including 30-day complication rates, method of operation and conversion rates. A total of 1189 patients were recruited across 27 centres. The NAR across all centres was 19.0%. 98.2% of appendicectomies were performed with a laparoscopic-first approach. The rate of conversion from laparoscopy to open operation was 2.4%. 9.4% of patients were recorded as having one or more of the following complications: readmission (6.6%), surgical site infection (1.9%), intra-abdominal abscess (2.7%) or further intervention (1.5%). Patients who had an open operation had higher rates of readmission and surgical site infection. The NAR found in this study is within the traditional measures of acceptance; however, this rate is high when measured against modern international benchmarks.


Ultrafast plasmon polaritons doubly resonant on a single silver nanoshell.
Ultrafast surface plasmon polaritons (SPPs) were observed in a silver nanoshell grating, which was produced by depositing a roughly sinusoidal dielectric grating with a continuous layer of silver. Two SPP modes were observed to propagate along the top and bottom surfaces of the silver nanoshell, modulating the reflection spectra in the space above and below the silver nanoshell, respectively. These two SPP modes are located independently at a shorter and a longer wavelength, exciting the asymmetric and symmetric oscillation of the plasmonic electrons, respectively. The asymmetric mode was excited by the diffraction anomaly along the silver/air interface, whereas, the symmetric by the waveguide mode within the ITO grating layer, which was defined by the high reflection at the ITO/silver interface and the total reflection at the ITO/substrate interface. Different optical switching performance with different lifetimes was measured for the two resonance modes.


A zinc finger HIT domain-containing protein, ZNHIT-1, interacts with orphan nuclear hormone receptor Rev-erbbeta and removes Rev-erbbeta-induced inhibition of apoCIII transcription.
The orphan receptors, Rev-erbalpha and Rev-erbbeta, are members of the nuclear receptor superfamily and specifically repress apolipoprotein CIII (apoCIII) gene expression in rats and humans. Moreover, Rev-erbalpha null mutant mice have elevated very low density lipoprotein triacylglycerol and apoCIII levels. However, ligands for Rev-erb are unknown and the regulatory mechanism of Rev-erb is poorly understood. Conceivably, cofactors for Rev-erb may play an important role in the regulation of lipid metabolism. In this study, a zinc finger HIT domain-containing protein, ZNHIT-1, interacted with Rev-erbbeta. ZNHIT-1 was found to be a conserved protein in eukaryotes and was highly abundant in human liver. Furthermore, ZNHIT-1 was identified as a nuclear protein. Serial truncated fragments and substitution mutations established a putative nuclear localization signal at amino acids 38-47 of ZNHIT-1. A putative ligand-binding domain of Rev-erbbeta and the FxxLL motif of ZNHIT-1 were required for their interaction. Finally, ZNHIT-1 was recruited by Rev-erbbeta to the apoCIII promoter and removed the Rev-erbbeta-induced inhibition of apoCIII transcription. These findings demonstrate that ZNHIT-1 functions as a cofactor to regulate the activity of Rev-erbbeta, and may play a role in lipid metabolism.


Relationship between white matter hyperintensities volume and the circle of Willis configurations in patients with carotid artery pathology.
We aimed to assess if there is a difference of distribution and volume of white matter hyperintensities (WMH) in the brain according to the Circle of Willis (CoW) configuration in patients with carotid artery pathology. One-hundred consecutive patients (79 males, 21 females; mean age 70 years; age range 46-84 years) that underwent brain MRI before carotid endarterectomy (CEA) were included. FLAIR-WMH lesion volume was performed using a semi-automated segmentation technique and the status of the circle of Willis was assessed by two neuroradiologists in consensus. We found a prevalence of 55% of variants in the CoW configuration; 22 cases had one variants (40%); 25 cases had two variants (45.45%) and 8 cases showed 3 variants (14.55%). The configuration that was associated with the biggest WMH volume and number of lesions was the A1+PcoA+PcoA. The PcoA variants were the most prevalent and there was no statistically significant difference in number of lesions and WMH for each vascular territory assessed and the same results were found for AcoA and A1 variants. Results of our study suggest that the more common CoW variants are not associated with the presence of an increased WMH or number of lesions whereas uncommon configurations, in particular when 2 or more segment are missing increase the WMH volume and number of lesions. The WHM volume of the MCA territory seems to be more affected by the CoW configuration.


Childbirth Fear: Relation to Birth and Care Provider Preferences.
The purpose of this study was to assess how preferences for place of birth and mode of birth relate to different dimensions of childbirth fear and whether there is an association between Canadian women's prenatal fear of childbirth and the type and quality of prenatal care they received. A link to an online survey was posted on Canadian pregnancy and birth websites; 409 women completed the survey that included sociodemographic questions, questions about the current pregnancy and previous pregnancy experiences (if applicable), and the Childbirth Fear Questionnaire, a validated 40-item scale that measures 9 dimensions of childbirth fear. Women under physician care and those with a preference for cesarean birth were generally more fearful of pain associated with vaginal birth, fear of loss of sexual pleasure and attractiveness, and fear of harm to themselves or their infant. Conversely, women under the care of midwives and women who preferred to give birth vaginally were more fearful of interventions. Women who preferred a cesarean birth were significantly more likely to report that fear of childbirth interfered with daily functioning, compared to women who preferred a vaginal birth. Satisfaction with care was associated with lower scores on the Childbirth Fear Questionnaire full and subscales, especially among midwifery clients. At present there are no guidelines in Canada or the United States for the treatment and/or referral of pregnant women who suffer from childbirth fear. Until such guidelines are developed, findings from the current study can help maternity care providers identify and address specific fears among women in their care and understand how different fear domains relate to care provider choice, satisfaction with care, and women's preferences for place and mode of birth.


Immune Escape by Non-coding RNAs of the Epstein Barr Virus.
Epstein Barr virus (EBV) is one of the most successful pathogens of humans, persistently colonizing more than 95% of the adult human population. At the same time EBV encodes oncogenes that can readily transform human B cells in culture and threaten healthy virus carriers with lymphomagenesis. Cytotoxic lymphocytes have been identified in experimental models and by primary immunodeficiencies as the main protective immune compartments controlling EBV. EBV has reached a stalemate with these cytotoxic T and innate lymphocytes to ensure persistence in most infected humans. Recent evidence suggests that the non-coding RNAs of the virus contribute to viral immune escape to prevent immune eradication. This knowledge might be used in the future to attenuate EBV for vaccine development against this human tumor virus that was discovered more than 55 years ago.


LMI-based asymptotic stability analysis of neural networks with time-varying delays.
The problem of the global asymptotic stability for a class of neural networks with time-varying delays is investigated in this paper, where the activation functions are assumed to be neither monotonic, nor differentiable, nor bounded. By constructing suitable Lyapunov functionals and combining with linear matrix inequality (LMI) technique, new global asymptotic stability criteria about different types of time-varying delays are obtained. It is shown that the criteria can provide less conservative result than some existing ones. Numerical examples are given to demonstrate the applicability of the proposed approach.


Bioequivalence evaluation of two brands of ketoconazole tablets (Onofin-K and Nizoral) in a healthy female Mexican population.
A randomized, crossover study was conducted in 24 healthy female volunteers to compare the bioavailability of two brands of ketoconazole (200 mg) tablets; Onofin-K (Farmacéuticos Rayere S.A., Mexico) as the test and Nizoral (Janssen-Cilag, Mexico) as the reference products. The study was performed at the Clinical Pharmacology Research Center of the Hospital General de Mexico in Mexico City. Two tablets (400 mg) were administered as a single dose with 250 ml of water after a 12 h overnight fast on two treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 12 h. Plasma harvested was analysed for ketoconazole by a modified and validated HPLC method with UV detection in the range 400-14000 ng/ml, using 200 microl of plasma in a full-run time of 2.5 min. The pharmacokinetic parameters AUC(0-t), AUC(0-alpha), Cmax, Tmax and t(1/2) were determined from plasma concentrations of both formulations and the results discussed. AUC(0-t), AUC(0-alpha) and Cmax were tested for bioequivalence after log transformation of data, and no significant differences were found either in 90% classic confidence interval or in the Anderson and Hauck test (p < 0.05). Based on statistical analysis, it is concluded that Onofin-K is bioequivalent to Nizoral.


Developing clinical algorithm for identifying acute lumbar spondylolysis in elementary school children - Classification and regression tree analysis.
To develop a clinical algorithm for classifying acute lumbar spondylolysis from nonspecific low back pain in elementary school-aged patients using the classification and regression tree analysis. Medical records of 73 school-aged patients diagnosed with acute lumbar spondylolysis or nonspecific low back pain were retrospectively reviewed. Fifty-eight patients were examined for establishing an algorithm and 15 were employed for testing its performance. The following data were retrieved: age, gender, school grades, days after symptom onset, history of low back pain, days of past low back pain, height, weight, body mass index, passive straight leg raise test results, hours per week spent on sports activities, existence of spina bifida, lumbar lordosis angle, and lumbosacral joint angle. Classification and regression tree analyses were performed 150 times using the bootstrap and aggregating method. Then, the results were integrated by majority vote, establishing an algorithm. Lumbar lordosis angle, days after symptom onset, body mass index, and lumbosacral joint angle were the predictors for classifying those injuries. The algorithm can be used to identify elementary school-aged children with low back pain requiring advanced imaging investigation, although a future study with a larger sample population is necessary for validating the algorithm.


Adolescents, the Internet, and health literacy.
In this article, the development of the concept and measurement of "off-line" health literacy is charted, recent development and interest in adolescent off-line health literacy is explored, and how the Internet could be useful in assessing and improving adolescents' online and off-line health literacy skills is considered. The important issue of content filters will also be considered as it relates to adolescents' ability to retrieve online health information about sensitive issues.


Rhabdomyolysis as an initial presentation in a patient diagnosed with COVID-19.
The presence of rhabdomyolysis secondary to multiple infections has been reported, predominantly viral, but also bacterial and fungal. It is well known that COVID-19 can present a wide variety of complications during the course of infection; however, the presence of rhabdomyolysis as an initial condition has not been reported so far. We report a case of rhabdomyolysis as an initial presentation in a patient diagnosed with SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection.


Invasion and survival strategies of Anaplasma phagocytophilum.
Anaplasma phagocytophilum is an aetiological agent of human granulocytic ehrlichiosis, an emerging tick-borne zoonosis in the United States and Europe. This obligate intracellular bacterium is unique in that it colonizes polymorphonuclear leucocytes (neutrophils). Neutrophils are key players in innate immunity. These short-lived phagocytes ingest invading microorganisms and destroy them by various means, which include fusing the bacteria-containing phagosome with acidic lysosomes as well as directing toxic oxidative and proteolytic compounds into the phagosomal lumen. Its tropism for neutrophils indicates that A. phagocytophilum uses strategies for evading and/or neutralizing these microbicidal activities. This review focuses on some of the mechanisms that A. phagocytophilum uses for neutrophil adhesion, surviving within the hostile intracellular environment of its host neutrophil and for effectively disseminating to naïve host cells.


Immunoreactive trypsins in sera from dogs before and after induction of experimental pancreatitis.
Radioimmunoassays for anionic and cationic dog trypsins are described. Characterization of the immunoreactivities in sera from fasting dogs demonstrated the presence of the two proenzymes only. Fasting sera from 10 dogs contained anionic and cationic trypsinogen in concentrations between 17-110 micrograms/l and 7-19 micrograms/l, respectively. Induction of experimental pancreatitis in dogs was accompanied by a large increase of immunoreactive anionic and cationic trypsins in the circulation. During the progress of the pancreatitis, immunoreactive trypsin with larger molecular weight than trypsinogen appeared. This high molecular weight immunoreactive trypsin was not seen in serum after intravenous injection of pancreatic juice in dogs. The high molecular weight immunoreactive trypsin probably consists of trypsin in complex with protease inhibitors. In vitro studies showed that the immunoreactivity of trypsin decreased considerably after binding to alpha 1-antitrypsin or alpha-macroglobulins.


Reflections on "Nursing considered as moral practice.
This response to the preceding article by Gastmans, Dierckx de Casterle, and Schotsmans challenges the notion of "good care" as the ultimate goal of nursing practice, explores further the possible goals of nursing and how they may be identified, and presents six elements of professional caring along with their related virtues and moral obligations.


Hedgehog can drive terminal differentiation of amniote slow skeletal muscle.
Secreted Hedgehog (Hh) signalling molecules have profound influences on many developing and regenerating tissues. Yet in most vertebrate tissues it is unclear which Hh-responses are the direct result of Hh action on a particular cell type because Hhs frequently elicit secondary signals. In developing skeletal muscle, Hhs promote slow myogenesis in zebrafish and are involved in specification of medial muscle cells in amniote somites. However, the extent to which non-myogenic cells, myoblasts or differentiating myocytes are direct or indirect targets of Hh signalling is not known. We show that Sonic hedgehog (Shh) can act directly on cultured C2 myoblasts, driving Gli1 expression, myogenin up-regulation and terminal differentiation, even in the presence of growth factors that normally prevent differentiation. Distinct myoblasts respond differently to Shh: in some slow myosin expression is increased, whereas in others Shh simply enhances terminal differentiation. Exposure of chick wing bud cells to Shh in culture increases numbers of both muscle and non-muscle cells, yet simultaneously enhances differentiation of myoblasts. The small proportion of differentiated muscle cells expressing definitive slow myosin can be doubled by Shh. Shh over-expression in chick limb bud reduces muscle mass at early developmental stages while inducing ectopic slow muscle fibre formation. Abundant later-differentiating fibres, however, do not express extra slow myosin. Conversely, Hh loss of function in the limb bud, caused by implanting hybridoma cells expressing a functionally blocking anti-Hh antibody, reduces early slow muscle formation and differentiation, but does not prevent later slow myogenesis. Analysis of Hh knockout mice indicates that Shh promotes early somitic slow myogenesis. Taken together, the data show that Hh can have direct pro-differentiative effects on myoblasts and that early-developing muscle requires Hh for normal differentiation and slow myosin expression. We propose a simple model of how direct and indirect effects of Hh regulate early limb myogenesis.


Clinico-serologic co-relation in bi-directional ABO incompatible hemopoietic stem cell transplantation.
The ABO blood group system is of prime significance in red cell transfusion and organ transplantation. However, ABO compatibility is not critical in allogenic hemopoietic stem cell transplantation (HSCT) and approximately 40-50% of hemopoietic stem cell transplants are ABO incompatible. This incompatibility may be major, minor or bi-directional. Though there are descriptions of transfusion practice and protocols in ABO incompatible HSCT, there are considerable variations and transfusion support in these patients can be very challenging. The immunohematologic observations in two cases of bi-directional ABO incompatible HSCT have been described, and clinico-serologic correlation has been attempted. In both cases, peripheral blood stem cell harvests were obtained using the Cobe spectra cell separator. Immunohematologic assessments in the donor and recipient were done as a part of pre HSCT evaluation. Both the standard tube technique and column agglutination method (Ortho Biovue Micro Bead System) was used. Antibody screen was done by column agglutination method using three cell panel (Surgiscreen cells). Isoagglutinin titration was done by the master dilution method and standard validated techniques were used. The pattern of laboratory findings in the two cases was different and so were the clinical outcomes. Although there was early engraftment in the first case, the second case developed pure red cell aplasia and this was well-reflected in the immunohematologic assessments. Immunohematologic assessment correlated well with the clinical picture and could be used to predict clinical outcome and onset of complications in ABO incompatible HSCT.


Evaluation of Sorbitol-Methanol Co-Feeding Strategy on Production of Recombinant Human Growth Hormone in Pichia Pastoris.
Recombinant protein production in Pichia pastoris is based on alcohol oxidase promoters which are regulated by methanol. However, the use of methanol has several disadvantages, which is why current trends in bioprocess development with Pichia pastoris (P. pastoris) are focusing on methanol mixed feeding strategies. This work aimed to develop a new experimental method and compare the effect of various fractions of sorbitol in mixed feeding strategy with stepwise addition of methanol to maximize the productivity of human growth hormone. Accordingly, fed-batch culture performed with a mixed feed of sorbitol/methanol. Sorbitol at concentrations of 30, 40, 50 and 60 gram per liter was added in batch-wise mode to the medium at the beginning of induction phase and the rate of methanol addition was increased stepwise during the first 12 h of production and then kept constant. In order to understand the effects of various co-substrate feeding strategies on P. pastoris and its production of hGH, cell mass, dry cell weight, total protein, hGH expression level and hGH concentration were analyzed and the results compared with the basic feeding protocol using one-way analysis of variance (ANOVA). According to the obtained results, sorbitol at a concentration of 50 g/L could significantly increase the production yield. Under such optimal conditions cell biomass was 108 g/L (DCW), total protein was 0.807 g/L, expression level was 83.1% and rhGH concentration was 0.667 g/L following 30 h induction.


Nivalenol, a main Fusarium toxin in dietary foods from high-risk areas of cancer of esophagus and gastric cardia in China, induced benign and malignant tumors in mice.
This is the first report that a Fusarium toxin nivalenol (NIV) naturally existing at high levels in dietary food in high-risk areas of cancer of esophagus and gastric cardia in China induced benign and malignant tumors in mice. The levels of two Fusarium toxins, nivalenol and deoxynivalenol (DON) were quantitated using high performance liquid chromatography (HPLC) in a total of 97 samples of dietary wheat flour, barley and corn collected from families in two areas with high mortality rate of cancer of esophagus and gastric cardia (132/100,000), Linxian, Henan province and Cixiang, Hepei province, China. The mean level of NIV and DON in three dietary foods was 830+/-927 microg/kg (range 584-1,780 microg/kg) and 4,281+/-6,114 microg/kg (range 732-10,980 microg/kg) respectively. The highest mean level of NIV was 1,780+/-1,705 microg/kg found in barley from Linxian, that of DON was 10,980+/-10,139 microg/kg found in corn from Cixiang. NIV was undetectable in 2 samples of rice from USA. The mean levels of NIV in three main dietary foods in those two high-risk areas were estimated at 400 to 800-fold higher than that in the USA, where NIV was undetectable in dietary food, and the mortality rate of esophageal cancer is <5/100,000 in white Caucasians in the USA, (odds ratio was estimated at 17-34, p<0.000005). These data suggest that Linxian and Cixiang peasants who consumed a diet with high NIV had significantly higher risk for developing esophageal cancer than the US residents who consumed food without or with negligible amounts of NIV. Three repeated experiments were performed using Balb/C mice with inter-mittent application of NIV, alternate with 12-Tetradeconoyl-phorbol-13-acetate (TPA) application on skin. Papillomas and carcinomas developed in a total of 23/49 (47%) mice that survived 11-60 weeks of experiments. Among all the tumors, 4 carcinomas in 3 mice were identified. No tumors were found in the 60 control mice applying either TPA or acetone (solvent) only on skin.


Frequency analysis of temperature-dependent interferometric signal for the measurement of the temperature coefficient of refractive index.
A method of frequency analysis for the measurement of the temperature coefficient of refractive index (dn/dT) using a Fabry-Perot interferometer was developed and tested against ethanol and water. The temperature-dependent interferometric signal described by Airy's formula was analyzed in both the temperature and frequency domains. By fast Fourier transform, a low-pass filter was designed and employed to eliminate the noise superimposed on the signal. dn/dT was determined accurately from the noise-removed signal by peak analysis. Furthermore, the signal frequency parameters may be utilized for the material thermophysical property characterization. This method lays the foundation for an online dn/dT instrument for monitoring chemical processes.


Mesenchymal stem cells from sternum: the type of heart disease, ischemic or valvular, does not influence the cell culture establishment and growth kinetics.
In an attempt to increase the therapeutic potential for myocardial regeneration, there is a quest for new cell sources and types for cell therapy protocols. The pathophysiology of heart diseases may affect cellular characteristics and therapeutic results. To study the proliferative and differentiation potential of mesenchymal stem cells (MSC), isolated from bone marrow (BM) of sternum, we made a comparative analysis between samples of patients with ischemic (IHD) or non-ischemic valvular (VHD) heart diseases. We included patients with IHD (n = 42) or VHD (n = 20), with average age of 60 years and no differences in cardiovascular risk factors. BM samples were collected (16.4 ± 6 mL) and submitted to centrifugation with Ficoll-Paque, yielding 4.5 ± 1.5 × 107 cells/mL. Morphology, immunophenotype and differentiation ability had proven that the cultivated sternal BM cells had MSC features. The colony forming unit-fibroblast (CFU-F) frequency was similar between groups (p = 0.510), but VHD samples showed positive correlation to plated cells vs. CFU-F number (r = 0.499, p = 0.049). The MSC culture was established in 29% of collected samples, achieved passage 9, without significant difference in expansion kinetics between groups (p > 0.05). Dyslipidemia and the use of statins was associated with culture establishment for IHD patients (p = 0.049 and p = 0.006, respectively). Together, these results show that the sternum bone can be used as a source for MSC isolation, and that ischemic or valvular diseases do not influence the cellular yield, culture establishment or in vitro growth kinetics.


The Effect of Zirconia Nanoparticles on Thermal, Mechanical, and Corrosion Behavior of Nanocomposite Epoxy Coatings on Steel Substrates.
Zirconia (ZrO2) nanoparticles (1-3 wt.%) were incorporated into the epoxy matrix using the ultra-sonication mixing method of dispersion to manufacture nanocomposite coatings. An automatic applicator was used to prepare the coating samples on a stainless steel substrate. The influence of ZrO2 nanoparticles on the physicochemical characteristics of epoxy coatings was evaluated using energy dispersive X-ray spectroscopy (EDS), field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), thermos-gravimetric analysis (TGA), elastic modulus, and micro-hardness measurement with the nano-indentation technique. The corrosion stability during immersion in 3.5% NaCl solution was monitored using electrochemical impedance spectroscopy (EIS). All ZrO2-containing coatings showed better corrosion stability and adhesion than pure epoxy coating. Epoxy coating incorporated with 2% ZrO2 exhibited the greatest values of corrosion resistance and adhesion due to the effect of nanoparticle properties and their better de-agglomeration in the epoxy matrix than pure epoxy coating.


Clearance of human herpesvirus 8 from blood and regression of leukopenia-associated aggressive classic Kaposi's sarcoma during interferon-alpha therapy: a case report.
A human immunodeficiency virus-negative woman with severe classic Kaposi's sarcoma, idiopathic leukopenia, and massive spread of human herpesvirus 8 (HHV-8) in circulating cells showed stable disease remission in response to systemic interferon-alpha treatment that was accompanied by increased CD3(+) and CD4(+) T cell numbers and complete clearance of HHV-8 from the circulation. These results suggest a direct relationship between HHV-8 clearance from blood and regression of Kaposi's sarcoma and are consistent with the in vitro inhibitory effects of interferon-alpha on HHV-8 infection.


Temporal Expression of Genes in Biofilm-Forming Ocular Candida albicans Isolated From Patients With Keratitis and Orbital Cellulitis.
To study antibiotic susceptibility and biofilm-forming potential of ocular isolates of Candida albicans along with gene expression. Seven clinical isolates of C. albicans (keratitis-6 and orbital cellulitis-1) were evaluated. Biofilm formation in one isolate was monitored by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Expression of 27 genes (real-time PCR) associated with biofilm formation and virulence was compared between biofilm-positive and biofilm-negative ocular C. albicans isolates. The temporal expression (4 to 72 hours) of the 27 overexpressed genes was also determined. Similar studies were also done with biofilm-positive and biofilm-negative nonocular C. albicans. Four of seven ocular C. albicans isolates exhibited the potential to form biofilm, one of which was resistant to three antifungals, whereas three were susceptible to all. SEM studies indicated that biofilm increased from two to three adherent layers of cells at 24 hours to multiple layers by 72 hours. CLSM showed that biofilm thickness increased from 5.2 μm at 24 hours to 17.98 μm at 72 hours. Upregulation of 27 genes involved in virulence and biofilm formation was observed both in the ocular and nonocular C. albicans positive for biofilm formation and compared to the respective non-biofilm-forming C. albicans. The results also indicated similarity in expression of genes between biofilm-forming ocular and nonocular pathogenic C. albicans. Temporal expression of the 27 genes (involved in adhesion, initiation, maturation, and dispersal stages of biofilm) in the biofilm-positive ocular isolate indicated that expression pattern followed four different patterns. This is the first study showing similarity in expression of genes in biofilm-forming ocular and nonocular isolates of C. albicans, suggesting that upregulated genes could serve as a potential target for developing therapeutic strategies.


Tannic Acid-Iron Complex-Based Nanoparticles as a Novel Tool against Oxidative Stress.
Accumulation of reactive oxygen species in cells leads to oxidative stress, with consequent damage for cellular components and activation of cell-death mechanisms. Oxidative stress is often associated with age-related conditions, as well as with several neurodegenerative diseases. For this reason, antioxidant molecules have attracted a lot of attention, especially those derived from natural sources─like polyphenols and tannins. The main issue related to the use of antioxidants is their inherent tendency to be oxidized, their quick enzymatic degradation in biological fluids, and their poor bioavailability. Nanomedicine, in this sense, has helped in finding new solutions to deliver and protect antioxidants; however, the concentration of the encapsulated molecule in conventional nanosystems could be very low and, therefore, less effective. We propose to exploit the properties of tannic acid, a known plant-derived antioxidant, to chelate iron ions, forming hydrophobic complexes that can be coated with a biocompatible and biodegradable phospholipid to improve stability in biological media. By combining nanoprecipitation and hot sonication procedures, we obtained three-dimensional networks composed of tannic acid-iron with a hydrodynamic diameter of ≈200 nm. These nanostructures show antioxidant properties and scavenging activity in cells after induction of an acute chemical pro-oxidant insult; moreover, they also demonstrated to counteract damage induced by oxidative stress both in vitro and on an in vivo model organism (planarians).


Adverse drug events identified by triggers at a teaching hospital in Brazil.
Adverse drug events (ADEs) are one of the most frequent causes of patient harm resulting from medical interventions, especially among inpatients. This study aimed to evaluate the incidence of ADEs and characterise them in terms of degree of harm, medication implicated and patient symptoms, at a Brazilian university hospital. This is a retrospective study of chart review. The method, developed by the Institute for Healthcare Improvement, uses triggers to identify possible ADEs. The study population comprised adult inpatients at least 15 years old. Obstetric patients and those hospitalised for less than 48 hours were excluded. Time spent in the intensive care unit was not considered for the purposes of this study. Patients were selected on the basis of simple random sampling of records of patients discharged from January to July 2008. The records selected were reviewed by a multidisciplinary team. The indicators of ADE incidence were patients with ADEs and ADE rate per 100 patients. Patients with and without ADE were compared in the bivariate analysis. To identify the drugs classes most often associated with events, the number of prescriptions of each class of drug was related to the number of events assigned to it. The 240 inpatients studied were of mean age 50.8 (SD = 20.0) years, and mostly male (63.8%). A total of 44 ADEs were identified in 35 patient records, with 14.6% of patients presenting ADE and a rate of 18.3% ADEs per 100 patients. The most frequent were skin rash and nausea and vomiting, but severe ADEs were also identified. In the bivariate analysis long hospital stay and use of 10 or more drugs were associated with the occurrence of ADEs (p-value < 0.01). The drug classes associated with the highest number of events were anti-infective. About 1/6 of the hospitalized patients in a teaching hospital showed adverse events what is, by itself, cause for concern. Increased number of prescribed drugs and greater period of hospitalization appear to favour the occurrence of these events. In the future studies with higher number of patients may offer evidences of the association.


The future is now: frontiers on display at Yale-NAVBO cardiovascular inflammation and remodeling symposium 2014.
Earlier this year, 200 researchers from across the globe gathered at the Omni New Haven Hotel at Yale University in New Haven, Connecticut, for 3 days of talks from 30 of the leading pioneers in modern cardiovascular medicine. From May 8 to 10, 2014, scientists discussed and dissected topics ranging from the clinical treatment of atherosclerosis to the molecular biology of leukocyte-endothelial cell interactions. With other sessions exploring vascular malformation and aneurysm, hypertension, the endothelial-mesenchymal transition (endo-MT), and the role of metabolism in cardiovascular disease, conference participants gained striking insights into rapid advances and ongoing challenges in the field of cardiovascular inflammation and remodeling.


A second locus and new alleles in the major histocompatibility complex class II (ELA-DQB) region in the horse.
More than two nucleotide sequences of the second exon of the ELA-DQB region retrieved from a single animal and two different sequences isolated from horses homozygous in the major histocompatibility complex (MHC) region by descent indicated the existence of at least two ELA-DQB loci at the genomic level. New alleles detected by polymerase chain reaction single strand conformation polymorphism (SSCP) and defined by nucleotide sequencing of the second exon of the DQB gene(s) were described. Based on the level of nucleotide sharing, at least two groups of alleles were shown to exist. The newly defined alleles belonged preferentially to one of the groups. However, their specific locus assignment was not possible from the data collected. At least one of these alleles was shown to be transcribed. No frame-shift mutations were identified among the new alleles, although one pseudoallele containing a stop codon was identified at the genomic DNA level.


Bleeding patterns during continuous estradiol with different sequential progestogens therapy.
: To evaluate the effects on monthly bleeding of four different progestogens administered in association with transdermal estradiol in a continuous sequential estrogen-progestin therapy (CS-EPT). : This prospective, open, randomized, clinical trial included 100 healthy postmenopausal women. Patients were randomized into four treatment groups, each consisting of 25 women. Treatment consisted of 50 mug/day transdermal 17beta-estradiol for all women combined to receive four different progestogens (group A: medroxyprogesterone acetate, 10 mg/day; group B: nomegestrol acetate, 5 mg/day; group C: dydrogesterone, 10 mg/day; group D: micronized progesterone, 200 mg/day) per os from the 14th to 25th day of each 28-day cycle. The duration of treatment was 12 cycles. Patients were asked to record in a daily diary the occurrence of any vaginal bleeding, the days of application of each patch, the days of assumption of the different progestogens, and the exact moment of bleeding onset. : A total of 937 cycles could be evaluated. In 690 cycles (73.6%), regular progestogen-related bleeding was reported. Among the other cycles, we observed 73 episodes of amenorrhea (7.8%, each one lasting one cycle), 78 episodes of irregular bleeding (8.3%), and 96 episodes of spotting (10.2%). Patients receiving nomegestrol acetate had a significantly higher incidence of regular progestogen-associated bleeding in comparison with those receiving medroxyprogesterone acetate or natural progesterone, and patients receiving dydrogesterone had a significantly higher incidence of regular progestogen-associated bleeding in comparison with those receiving natural progesterone. : Our data suggest that CS-EPT generally leads to regular withdrawal bleeding in women without uterine pathology. Micronized progesterone seems to induce more irregular bleeding episodes.


Intergenerational Transmission of BMI and Educational Outcomes in Children and Adolescents.
Individual differences in educational attainment (EA) and physical health, as indexed by body mass index (BMI), are correlated within individuals and across generations. The aim of our study was to assess the transmission of these traits from parents to their offspring in childhood and adolescence. We analyzed BMI and EA in 13,916 families from the Netherlands. Data were available for 27,577 parents (mean age 33) and 26,855 of their offspring at 4 and 12 years of age. We employed structural equation modeling to simultaneously estimate the phenotypic transmission of BMI and EA from parents to offspring, the spousal correlations, and the residual child BMI-EA associations after accounting for intergenerational transmission and testing for gender differences therein. We found a significant intergenerational transmission of BMI to BMI in childhood (age 4; standardized regression coefficient β = .10) and adolescence (age 12; β = .20), and of EA to academic achievement in adolescence (β = .19). Cross-trait parent-to-offspring transmission was weak. All transmission effects were independent of parent or offspring gender. We observed within-person EA-BMI correlations that were negative in parents (∼-.09), positive in children (∼.05) and negative in adolescents (∼-.06). Residual EA-BMI were positive in children (∼.05) and insignificant in adolescents. Spousal correlations were .46 for EA, .21 for BMI, and ∼-.09 cross-trait. After accounting for spousal correlations, the intergenerational transmission for BMI and EA is mainly predictive within, but not across, traits. The within-person correlation between BMI and EA can change in direction between childhood and adulthood.


Synthesis, Characterization and Fabrication of Graphene/Boron Nitride Nanosheets Heterostructure Tunneling Devices.
Various types of 2D/2D prototype devices based on graphene (G) and boron nitride nanosheets (BNNS) were fabricated to study the charge tunneling phenomenon pertinent to vertical transistors for digital and high frequency electronics. Specifically, G/BNNS/metal, G/SiO2, and G/BNNS/SiO2 heterostructures were investigated under direct current (DC-bias) conditions at room temperature. Bilayer graphene and BNNS were grown separately and transferred subsequently onto the substrates to fabricate 2D device architectures. High-resolution transmission electron microscopy confirmed the bilayer graphene structure and few layer BNNS sheets having a hexagonal B3-N3 lattice. The current vs voltage I(V) data for the G/BNNS/Metal devices show Schottky barrier characteristics with very low forward voltage drop, Fowler-Nordheim behavior, and 10-4 Ω/sq. sheet resistance. This result is ascribed to the combination of fast electron transport within graphene grains and out-of-plane tunneling in BNNS that circumvents grain boundary resistance. A theoretical model based on electron tunneling is used to qualitatively describe the behavior of the 2D G/BNNS/metal devices.


Preliminary Data on Some Behavioral Changes Induced by Short-Term Intraperitoneal Oxytocin Administration in Aged Rats.
Oxytocin (OT) is a well-known neuropeptides which together with vasopressin, melatonin, insulin and other hormones can alter both behavior and physiological or neuronal functions. This growing interest on OT roles is also based on the demonstrated beneficial effects as a stress reliever and a social bonding agent. The association between old age and OT was only vaguely studied. Little or few is known on the effect of the OT hormone on the old body. Hereby, we present our preliminary results in the research on behavioral changes regarding the intraperitoneal administration of OT in aged rats. OT was administered for 8 days in Wistar aged rats in parallel with saline administration for control group. Behavioral markers were assessed in some specific behavioral tasks, such as the Y-Maze test for short-term working memory, Open Field test, Elevated Plus Maze, and Forced Swim test for anxious and depressive behavior assessment, and Three-chambered Maze test for sociability assessment. Increased mobility and decreased anxiety behaviors were reported for the aged intraperitoneal OT-treated animals, as compared with controls, during FST and OFT, and respectively FST, EPM, and OFT. Also, decreased depressive-like behaviors were observed in the same animal group during FST and ST. Moreover, a decrease in anxiolytic behavior was observed as exposed to stressful stimuli (such as grooming behavior in OFT, and forced grooming behavior in ST), and as exposed to social stimuli (such as grooming behavior in TCT). Similarly, significant differences were obtained regarding the social behavior of the intraperitoneal OT-treated animal as compared to control group, the animals showing increased sociability and social preference for the stranger animal in TCT. However, no significant effects on the working memory (assessed as spontaneous alternation in YMT) were observed. Intraperitoneal administration of OT in aged rats has clear effects on anxious and depressive behavior, but no significant effects on the working memory. Also, several beneficial effects of OT on social preferences and sociability were observed.


Oestrogen, cognition and the maturing female brain.
Many women complain of memory and other cognitive difficulties at times that are associated with changes in ovarian steroid levels. However, the biological mechanisms through which ovarian steroids exert these effects remains poorly understood. Furthermore, the effect of hormone therapy, especially oestrogen therapy, on cognition and brain function in healthy women, and its role in the prevention of Alzheimer's disease, remains controversial. Here, we review the evidence that, in healthy women, ovarian steroids/oestrogen affects brain regions crucial to higher cognitive function at the macroscopic, microscopic, functional and neurotransmitter levels.


[Gegen Qinlian decoction activates PPARγ to ameliorate adipocytic insulin resistance in diabetic SD rats and IR-3T3-L1 adipocytes].
To investigate the effects of Gegen Qinlian decoction(GQD) in improving adipocytic insulin resistance(IR) and explore its related molecular mechanism. Diabetic rats models were induced by high glucose and high-fat diet with a small dose of streptozotocin, and after GQD treatment for 3 months, blood biochemical indexes such as fasting blood-glucose(FBG), insulin, glycosylated serum protein(GSP) and HOMA-IRI were detected and assessed. After the total RNA was extracted from the adipose tissue of diabetic SD rats, PPARγ, ADPN, GLUT4, GLUT2, ACACA and ACACB mRNA expression levels were separately detected by qPCR. Then, stable IR-3T3-L1 adipocyte model was built with 1 μmol•L⁻¹ dexamethasone. After the cell viability was detected by CCK-8 assay, 5%, 10% and 15% GQD-containing serum(GQD-CS) were respectively used to treat IR-3T-L1 adipocytes for 24 h. The contents of glucose, nonesterified fatty acid(NEFA) and adiponectin in cell culture supernatants were separately detected whereas the intracellular triglyceride(TG) contents of IR-3T3-L1 adipocytes were also measured. The ADPN, PPARγ and GLUT4 mRNA and protein expression levels were respectively detected by qPCR and Western blot in IR-3T3-L1 adipocytes. Results showed that GQD significantly decreased fasting blood glucose, insulin and GSP(P<0.01), and down-regulated HOMA-IRI(P<0.05) after the high-fat diet/streptozotocin-induced diabetic SD rats were treated for three months, with a good hypoglycemic effect. Moreover, PPARγ, ADPN, GLUT4, GLUT2, ACACA and ACACB mRNA expression levels were significantly elevated in the adipose tissue of GQD-treated diabetic SD rats. The 5%, 10% and 15% GQD-CS significantly increased glucose consumption of IR-3T3-L1 adipocytes at 24 h treatment(P<0.01), significantly decreased the intracellular TG content (P<0.01), and down-regulated NEFA to a certain extent but not significantly. Moreover, GQD-CS significantly up-regulated GLUT4 and ADPN expression. The results indicated that GQD could activate PPARγ to ameliorate adipocytic insulin resistance in the diabetic SD rats and IR-3T3-L1 adipocytes.


Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution.
Teleosts comprise about half of all vertebrate species and exhibit an extraordinary diversity of adult pigment patterns that function in shoaling, camouflage, and mate choice and have played important roles in speciation. Here, we review studies that have identified several distinct neural crest lineages, with distinct genetic requirements, that give rise to adult pigment cells in fishes. These lineages include post-embryonic, peripheral nerve-associated stem cells that generate black melanophores and iridescent iridophores, cells derived directly from embryonic neural crest cells that generate yellow-orange xanthophores, and bipotent stem cells that generate both melanophores and xanthophores. This complexity in adult chromatophore lineages has implications for our understanding of adult traits, melanoma, and the evolutionary diversification of pigment cell lineages and patterns.


Draft Genome Sequence of Zygosaccharomyces mellis CA-7, Isolated from Honey.
In this study, we report the draft genome sequence of Zygosaccharomyces mellis CA-7, isolated from purchased honey imported from Canada. The 10.19-Mb genome contains 4,963 gene models. To our knowledge, this annotated genome sequence is the first from the species Z. mellis and will contribute to a better understanding of the osmotolerance of microorganisms in high-sugar products.


hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of 'MET-addicted' cancers.
The tyrosine kinase receptor encoded by the MET oncogene is a major player in cancer. When MET is responsible for the onset and progression of the transformed phenotype (MET-addicted cancers), an efficient block of its oncogenic activation results in potent tumor growth inhibition. Here we describe a molecular engineered MET antibody (hOA-DN30) and validate its pharmacological activity in MET-addicted cancer models in vitro and in vivo. Pharmacokinetics and safety profile in non-human primates have also been assessed. hOA-DN30 efficiently impaired MET activation and the intracellular signalling cascade by dose and time dependent removal of the receptor from the cell surface (shedding). In vitro, the antibody suppressed cell growth by blocking cell proliferation and by concomitantly inducing cell death in multiple MET-addicted human tumor cell lines. In mice xenografts, hOA-DN30 induced an impressive reduction of tumor masses, with a wide therapeutic window. Moreover, the antibody showed high therapeutic efficacy against patient-derived xenografts generated from MET-addicted gastric tumors, leading to complete tumor regression and long-lasting effects after treatment discontinuation. Finally, hOA-DN30 showed a highly favorable pharmacokinetic profile and substantial tolerability in Cynomolgus monkeys. hOA-DN30 unique ability to simultaneously erase cell surface MET and release the 'decoy' receptor extracellular region results in a paramount MET blocking action. Its remarkable efficacy in a large number of pre-clinical models, as well as its pharmacological features and safety profile in non-human primates, strongly envisage a successful clinical application of this novel single-arm MET therapeutic antibody for the therapy of MET-addicted cancers.


The interpretation of kinetic data for enzyme-catalysed reactions involving three substrates.
The analysis and interpretation of initial-rate data for reactions involving three substrates, obtained in suitably designed experiments, are discussed. Possible mechanisms for such reactions are classified, the rate equations are compared and the extent to which they can be distinguished experimentally is considered.


Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD.
Ten-year follow-up results from the Parkinson's Disease Research Group of the United Kingdom trial demonstrated that there were no long-term advantages to initiating treatment with bromocriptine compared with l-dopa in early Parkinson disease (PD). Increased mortality in patients on selegiline combined with l-dopa led to premature termination of this arm after 6 years. Between 1985 and 1990, 782 patients were recruited into an open pragmatic multicenter trial and were randomized to l-dopa/decarboxylase inhibitor (DDCI), l-dopa/DDCI plus selegiline, or bromocriptine. The main endpoints were mortality, disability, and motor complications. For final follow-up, health-related quality of life and mental function were also assessed. Median duration of follow-up at final assessment was 14 years in the 166 (21%) surviving participants who could be contacted. After adjustment for baseline characteristics, disability scores were better in the l-dopa than in the bromocriptine arm (Webster: 16.6 vs 19.8; p = 0.03; Northwestern University Disability: 34.3 vs 30.0, p = 0.05). Physical functioning (difference 20.8; 95% CI 10.0, 31.6; p < 0.001) and physical summary scores (difference 5.2; 95% CI 0.7, 9.7; p = 0.03) on the 36-item short-form health survey were also superior on l-dopa. Differences in mortality rates and prevalence of dyskinesias, motor fluctuations, and dementia were not significantly different. Initial treatment with the dopamine agonist bromocriptine did not reduce mortality or motor disability and the initially reduced frequency in motor complications was not sustained. We found no evidence of a long-term benefit or clinically relevant disease-modifying effect with initial dopamine agonist treatment.


Predictors of outcomes in hematopoietic cell transplantation for Fanconi anemia.
Allogeneic hematopoietic cell transplantation (HCT) remains the only cure for the hematologic manifestations of Fanconi anemia (FA). We performed retrospective predictor analyses for HCT outcomes in FA for pediatric and young adult patients transplanted between 2007 and 2020 across three large referral institutions. Eighty-nine patients, 70 with bone marrow failure +/- cytogenetic abnormalities, 19 with MDS/AML, were included. Five-year overall survival (OS) was 83.2% and event-free survival (EFS) was 74%. Age ≥19, HLA mismatch and year of HCT were multivariable predictors (MVPs) for OS, EFS and treatment-related mortality (TRM). In the pediatric group, TCD was a borderline MVP (P = 0.059) with 5-year OS of 73.0% in TCD vs. 100% for T-replete HCT. The cumulative incidence of day 100 grade II-IV aGvHD and 5-year cGvHD were 5.6% and 4.6%, respectively. Relapse in the MDS/AML subgroup occurred in 4 patients (16%). Graft failure was seen in 9 patients (TCD 6/37 [16%]; T-replete 3/52 [5.7%]). Six patients developed malignancy after HCT. Survival chances after HCT for FA are excellent and associated with high engrafted survival and low toxicity. Age ≥19, HLA mismatch, year of transplant and 'TCD in the <19 years group' (although borderline) were found to be negative predictors for survival.


Inverse substrates: novel synthetic substrates for trypsin and related enzymes.
The kinetics of the reactions of trypsin and related enzymes with esters derived from p-amidinophenol have been studied. These esters were named "inverse substrates" with respect to their structure and kinetic characteristics. Preparation of a variety of acyltrypsins was carried out by use of these substrates. Spectral analysis of acyl trypsins carrying a reporter group provided valuable information on the microenvironments near the active site. Kinetic analysis of the behaviour of trypsin and related enzymes toward these novel-type substrates revealed characteristic function of the enzymes not manifested with typical substrates. These results were analyzed with a view to comparing the spatial requirements of the respective active site.


[Thyroid hormone resistance may course hypotonia in infancy].
Allan Herndon Dudley's syndrome (AHDS) is X-linked mental retardation and hypotonia caused by mutations in a thyroid hormone transporter gene - MCT8. The typical thyreoidea AHDS profile is elevated T3, low-normal T4 and normal or elevated thyroid stimulating hormone (TSH). Neonatal screening with TSH often does not identify AHDS in boys and therefore it is of paramount importance to screen boys who present with hypo-tonia and/or mental retardation with thyroidea profile. In the case report a four and a half month-old boy with develop-mental delay and hypotonia is described and diagnosed with AHDS. The finding of the typical thyroidea profile leads to the diagnosis which is confirmed by DNA analysis.


Whole-cell peroxidase test for identification of Legionella pneumophila.
A simple combined peroxidase-catalase test has been developed which is applicable to live bacterial cells. Known strains of Legionella pneumophila were differentiated from other species of Legionella by being peroxidase positive and catalase negative.


Effect of various lysosomotropic agents and microtubule disrupting drugs on the lactogenic and the mammogenic action of prolactin.
Various drugs added to the culture medium of rabbit mammary gland were assayed for their capacity to affect the lactogenic and the mammogenic activities of prolactin. Three lysosomotropic agents NH4Cl, chloroquine and methylamine which were previously demonstrated to inhibit the degradation of the hormone-receptor complex after its internalization (down-regulation) did not prevent the initiation of casein synthesis, of lactose synthetase activity and of DNA synthesis. Five microtubule disrupting drugs, colchicine, colcemid, vinblastin, podophyllotoxin and nocodazole inhibited the induction of casein and DNA synthesis by prolactin whereas two inactive analogues, trimethylcolchicinic acid and lumicolchicine had no effect. None of these drugs exhibited any general cytotoxic effect as judged by the capacity of the tissue to incorporate 14C aminoacids into total proteins and 3H-uridine into total RNA. The microtubule disrupting drugs did not greatly reduce the rate of casein synthesis in the cultured mammary tissue explanted from lactating rabbits. The data suggest that the down-regulation of prolactin receptor is not strictly required for the two considered prolactin activities. By contrast, the integrity of microtubules, or at least of structures in which tubulin is involved, is necessary to ensure a normal transmission of the prolactin information responsible for the initiation of milk and DNA synthesis. In addition, the fact that the lactogenic and the mammogenic activities of prolactin are affected by the same drugs suggests that these two properties of the hormone are mediated by cellular mechanisms which have at least one common step.


Rapid and highly informative diagnostic assay for H5N1 influenza viruses.
A highly discriminative and information-rich diagnostic assay for H5N1 avian influenza would meet immediate patient care needs and provide valuable information for public health interventions, e.g., tracking of new and more dangerous variants by geographic area as well as avian-to-human or human-to-human transmission. In the present study, we have designed a rapid assay based on multilocus nucleic acid sequencing that focuses on the biologically significant regions of the H5N1 hemagglutinin gene. This allows the prediction of viral strain, clade, receptor binding properties, low- or high-pathogenicity cleavage site and glycosylation status. H5 HA genes were selected from nine known high-pathogenicity avian influenza subtype H5N1 viruses, based on their diversity in biologically significant regions of hemagglutinin and/or their ability to cause infection in humans. We devised a consensus pre-programmed pyrosequencing strategy, which may be used as a faster, more accurate alternative to de novo sequencing. The available data suggest that the assay described here is a reliable, rapid, information-rich and cost-effective approach for definitive diagnosis of H5N1 avian influenza. Knowledge of the predicted functional sequences of the HA will enhance H5N1 avian influenza surveillance efforts.


Action and familiarity effects on self and other expert musicians' Laban effort-shape analyses of expressive bodily behaviors in instrumental music performance: a case study approach.
Self-reflective performance review and expert evaluation are features of Western music performance practice. While music is usually the focus, visual information provided by performing musicians' expressive bodily behaviors communicates expressiveness to musically trained and untrained observers. Yet, within a seemingly homogenous group, such as one of musically trained individuals, diversity of experience exists. Individual differences potentially affect perception of the subtleties of expressive performance, and performers' effective communication of their expressive intentions. This study aimed to compare self- and other expert musicians' perception of expressive bodily behaviors observed in marimba performance. We hypothesized that analyses of expressive bodily behaviors differ between expert musicians according to their specialist motor expertise and familiarity with the music. Two professional percussionists and experienced marimba players, and one professional classical singer took part in the study. Participants independently conducted Laban effort-shape analysis - proposing that intentions manifest in bodily activity are understood through shared embodied processes - of a marimbists' expressive bodily behaviors in an audio-visual performance recording. For one percussionist, this was a self-reflective analysis. The work was unfamiliar to the other percussionist and singer. Perception of the performer's expressive bodily behaviors appeared to differ according to participants' individual instrumental or vocal motor expertise, and familiarity with the music. Furthermore, individual type of motor experience appeared to direct participants' attention in approaching the analyses. Findings support forward and inverse perception-action models, and embodied cognitive theory. Implications offer scientific rigor and artistic interest for how performance practitioners can reflectively analyze performance to improve expressive communication.


Stepping Back and Listening: Staff Experiences of Using a Coaching Approach in an Acute Rehabilitation Ward for Older Adults.
Previous research has highlighted that acute care provision can lead to a loss of confidence, control, and independent functioning in older adult patients. In addition, it is recognized that interactions between patients and health care staff are central to the prevention of functional decline in patients. In this study, we aimed to affect the staff-patient relationship by implementing a coaching intervention in an older adult acute care setting. Here, we report on staff experiences of this coaching approach. Data were collected from 16 members of staff via semi-structured interviews, which were analyzed using thematic analysis. Four themes were identified: Putting a Label on It, Stepping Back and Listening, Identifying the Opportunities, and Working as Team. Our findings show that a coaching approach can be successful in getting staff to reconsider their interactions with patients and to focus on strategies that foster the independence and autonomy of older adult patients.


Inhibition by alpha factor of the glucose-induced activation of regulatory trehalase in Saccharomyces cerevisiae.
The enzyme activity of the regulatory trehalase (alpha, alpha-trehalose glycohydrolase; EC 184.108.40.206) in stationary-phase cells of Saccharomyces cerevisiae increased upon addition of glucose to cell suspensions. Such increase was temporarily retarded in the presence of alpha factor in the medium. The transient inhibition required the joined action of the pheromone-like factor and the protease inhibitor N-alpha-p-tosyl-L-lysine chloromethyl ketone. The inhibition of the glucose-induced activation of trehalase by alpha factor lends support to the involvement of adenosine 3',5'-cyclic monophosphate in the enzyme activation in vivo.


Deeper look into feedback practice in an Indonesian context: exploration of factors in undergraduate clinical settings.
The practice of feedback is influenced by the characteristics of students, teachers, and the clinical environment. Most studies on feedback have been conducted in Western settings with different sociocultural backgrounds to Indonesia. This study explores feedback in Indonesian clinical clerkship using a sociocultural lens and aims to provide an exemplar of adaptive practice relevant to non-Western settings. This qualitative study was conducted using an interpretive phenomenology approach. Data were collected through focus groups with students and teachers and interviews with program coordinators. Data were transcribed verbatim and grouped according to data sources, coded, and analyzed thematically. Themes identified from the focus group discussions and interviews were categorized as student, teacher, and environmental factors. Student factors include dependence on feedback, tendencies to use a group approach, difficulties recognizing social rules, a perceived lack of resilience, and tendencies to doubt praise. Factors related to teachers include a high level of expertise, being extremely busy, having a strong commitment, and being unsure of students' acceptance of feedback. Clinical environment factors influence interactions between teachers and learners and include high power distance and collectivistic values. A safe environment is needed to ensure effective feedback interactions. High power distance, collectivism, and generational characteristics of students likely impact feedback practice in clinical settings. Designing a safe environment is essential for effective feedback practice.