Critical dependence of calcium-activated force on width in highly compressed skinned fibers of the frog.
Force development by skinned frog semitendinosus fibers was studied at various levels of lateral compression to compare the results with intact fibers and to evaluate the limits on cross-bridge movements during isometric contraction. The skinned fibers were compressed osmotically using a high molecular weight polymer, dextran T500. Ca-activated force remained constant down to 58% of the fiber width (w0) after skinning, corresponding to a nearly twofold change in separation between the thin and thick filaments in the myofilament lattice. This agrees with the earlier result on intact fibers, and gives additional evidence that the cross-bridge mechanism for force generation is relatively insensitive to large changes in interfilament separation. Further compression, below 0.58 w0, produced a sharp drop in force, and the force was practically zero at a fiber width of 50%. The effect at high compression was the same at all pCa's, which indicates that the Ca sensitivity of the myofilaments is unaffected by radial compression. The stiffness of the fiber remained high in rigor in the presence of dextran, which indicates that the rigor cross-bridge attachment is not inhibited, and actually may be improved, with decreases in the interfilament space. Also, the drop in active force with the highest compression was similar when the compressed fibers were put in rigor before contraction, which suggests that the force drop also was not due to a hindrance to cross-bridge attachment. The results appear to exclude large motions such as tilting and rocking of the bridge as a rigid molecule, but suggest that at least some molecular movement is essential for force development; they also raise the possibility that there is a critical interfilament separation in the fiber, below which the cross-bridge cannot function.


Study of Variation and Latency of Wave V of Brain Stem Evoked Response Audiometry in North Central India.
The brainstem evoked response audiometry (BERA) is an objective electrophysiological method for assessing the auditory pathway from the auditory nerve to the brain stem. To access the hearing pathway by BERA and compare differences in latency of wave five associated with age, gender and side of ear (left and right) in our set up. Total 257 patients were selected, there were 125 males and 132 females. All patients with auditory and vestibular complaint were assessed and underwent otoscopic examination, Pure Tone Audiometry (free field audiometry in children), Impedence and BERA. The analysis revealed that there has been progressive rise in latency (mean) of wave V with age, with a significant rise in latency in elderly individuals above 60. The analysis also revealed that that latency (mean) was higher in males than females in corresponding age group, also latency was higher in right ear in females but no such statistically significant relation could be established in males. There is still a need to have standardized set of absolute latency and interwave latency peak difference. Also in such cases of inclusion and exclusion needs to be mentioned.


The reactivity of anti-peptide antibodies is a function of the atomic mobility of sites in a protein.
To study the nature of antigenic recognition, antibodies have been prepared against a set of peptide sequences representing both highly mobile and well-ordered regions of myohaemerythrin, based on X-ray crystallographic temperature factors. Anti-peptide antibodies against highly mobile regions react strongly with the native protein; anti-peptide antibodies from well-ordered regions do not. Mobility is a major factor in the recognition of the native protein by anti-peptide antibodies; this may be of general significance in protein-protein interactions.


Effect of fenoterol on immunological release of leukotrienes and histamine from human lung in vitro: selective antagonism by beta-adrenoceptor antagonists.
The inhibitory effects of fenoterol, a beta 2-adrenoceptor agonist, on the release of SRS-A leukotrienes and histamine from chopped human lung tissue were measured and selective beta-adrenoceptor antagonists used to investigate the nature of the receptors involved. Fenoterol 0.01-1.0 microM inhibited the antigen-induced release of SRS-A and histamine, but not the release induced by the calcium ionophore A23187. Propranolol 0.1 and 1.0 microM and butoxamine 10 and 100 microM significantly antagonized the effects of fenoterol 0.1 microM on SRS-A and histamine at concentrations which affect (beta 2-adrenoceptors, while atenolol 0.1 to 10 microM showed no antagonism at concentrations which affect beta 1-adrenoceptors. These results suggest that adrenoceptors in human lung which modulate the immunological release of SRS-A leukotrienes are of the beta 2-subtype as for histamine release.


Ecotoxicological response of Spirulina platensis to coexisted copper and zinc in anaerobic digestion effluent.
Copper ion (Cu2+) and zinc ion (Zn2+) are widely co-existent in anaerobic digestion effluent as typical contaminants. This work aims to explore how Cu2+-Zn2+ association affects physiological properties of S. platensis using Schlösser medium (SM) and sterilized anaerobic digestion effluent (SADE). Microalgae cells viability, biochemical properties, uptake of Cu2+ and Zn2+, and risk assessment associated with the biomass reuse as additives to pigs were comprehensively assessed. Biomass production ranged from 0.03 to 0.28 g/L in SM and 0.63 to 0.79 g/L in SADE due to the presence of Cu2+ and Zn2+. Peak value of chlorophyll-a and carotenoid content during the experiment decreased by 70-100% and 40-100% in SM, and by 70-77% and 30-55% in SADE. Crude protein level reduced by 4-41% in SM and by 65-75% in SADE. The reduction ratio of these compounds was positively related to the Cu2+ and Zn2+ concentrations. Maximum value of saturated and unsaturated fatty acids was both obtained at 0.3 Cu + 2.0 Zn (50.8% and 22.8%, respectively) and 25% SADE reactors (33.8% and 27.7%, respectively). Uptake of Cu in biomass was facilitated by Zn2+ concentration (> 4.0 mg/L). Risk of S. platensis biomass associated with Cu2+ was higher than Zn2+. S. platensis from SM (Cu2+ ≤ 0.3 mg/L and Zn2+ ≤ 4.0 mg/L) and diluted SADE (25% and 50% SADE) reactors could be used as feed additives without any risk (hazard index <1), which provides sufficient protein and fatty acids for pig consumption. These results revealed the promising application of using S. platensis for bioremediation of Cu2+ and Zn2+ in anaerobic digestion effluent and harvesting biomass for animal feed additives.


Nuclear resonant inelastic X-ray scattering at high pressure and low temperature.
A new synchrotron radiation experimental capability of coupling nuclear resonant inelastic X-ray scattering with the cryogenically cooled high-pressure diamond anvil cell technique is presented. The new technique permits measurements of phonon density of states at low temperature and high pressure simultaneously, and can be applied to studies of phonon contribution to pressure- and temperature-induced magnetic, superconducting and metal-insulator transitions in resonant isotope-bearing materials. In this report, a pnictide sample, EuFe2As2, is used as an example to demonstrate this new capability at beamline 3-ID of the Advanced Photon Source, Argonne National Laboratory. A detailed description of the technical development is given. The Fe-specific phonon density of states and magnetism from the Fe sublattice in Eu(57)Fe2As2 at high pressure and low temperature were derived by using this new capability.


Stigma and posttraumatic growth among COVID-19 survivors during the first wave of the COVID-19 pandemic in Malaysia: a multicenter cross-sectional study.
Contracting COVID-19 can cause negative and distressing psychological sequelae, but traumatic stressors may also facilitate the development of positive psychological change beyond an individual's previous level of adaptation, known as posttraumatic growth (PTG). As a result, studies have investigated the negative effects of COVID-19 on mental health, but data on PTG among patients who have recovered from COVID-19 remains limited. This study aims to evaluate the level of PTG and its associations with stigma, psychological complications, and sociodemographic factors among COVID-19 patients 6 months post-hospitalization. A cross-sectional online survey of 152 COVID-19 patients was conducted after 6 months of being discharged from Hospital Canselor Tuanku Muhriz, MAEPS Quarantine Center, or Hospital Sungai Buloh, Malaysia. Patients completed a set of questionnaires on sociodemographic and clinical data. The Posttraumatic Growth Inventory (PTGI-SF) was used to assess the level of PTG, the Kessler Psychological Distress (K6) was used to measure the degree of psychological distress, the General Anxiety Disorder-7 (GAD-7) was used to evaluate the severity of anxiety symptoms, the Patient Health Questionnaire (PHQ-9) was used to assess the severity of depression symptoms, and the Explanatory Model Interview Catalog Stigma Scale (EMIC-SS) was used to record the degree of perceived stigma toward COVID-19. The median PTGI SF score of the respondents was 40.0 (Interquartile range 16.0). Multivariable general linear model with bootstrapping (2,000 replications) revealed factors that significantly predicted PTG, which were at the higher level of the perceived stigma score, at 37 (B = 0.367, 95% CI = 0.041 to 0.691, p = 0.026), among the Malay ethnicity (B = 12.767, 95% CI 38 = 7.541 to 17.993, p < 0.001), retirees (B = -12.060, 95% CI = -21.310 to -2.811, p = 0.011), and those with a history of medical illness (B = 4.971, 95% CI = 0.096 to 9.845, p = 0.046). Experiencing stigma contributed to patients' PTG in addition to psychosocial factors such as ethnicity, history of medical illness, and retirement.


Mitotic and polytene chromosomes analysis of the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).
The Oriental fruit fly, Batrocera dorsalis s.s. (Hendel) is one of the most destructive agricultural pests, belonging to a large group of difficult to distinguish morphologically species, referred as the B. dorsalis complex. We report here a cytogenetic analysis of two laboratory strains of the species and provide a photographic polytene chromosome map from larval salivary glands. The mitotic complement consists of six chromosome pairs including a heteromorphic sex (XX/XY) chromosome pair. Analysis of the polytene complement has shown a total of five polytene chromosomes (10 polytene arms) that correspond to the five autosomes. The most important landmarks of each polytene chromosome and characteristic asynapsis at a specific chromosomal region are presented and discussed. Chromosomal homology between B. dorsalis and Ceratitis capitata has been determined by comparing chromosome banding patterns. The detection of chromosome inversions in both B. dorsalis strains is shown and discussed. Our results show that the polytene maps presented here are suitable for cytogenetic analysis of this species and can be used for comparative studies among species of the Tephritidae family. They also provide a diagnostic tool that could accelerate species identification within the B. dorsalis complex and could shed light on the ongoing speciation in this complex. Polytene chromosome maps can facilitate the development of biological control methods and support the genome mapping project of the species that is currently in progress.


Image Guidance Volume-Modulated Arc Radiation Therapy Concurrently With Nab-Paclitaxel Plus Cisplatin for Patients With Locally Advanced Cervical Cancer: A Single-Arm Dose Escalation Trial.
Nanoparticle albumin-bound (nab) paclitaxel has improved uptake by tumor cells in comparison to paclitaxel. The aim of this study was to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity (DLT) of nab-paclitaxel plus cisplatin with concurrent image guidance volume modulated arc therapy for locally advanced cervical cancer (LACC). This single-arm phase 1 trial followed the standard 3 + 3 dose escalation design. Patients with histologically proven stage IB2-IVA LACC were eligible. Image guidance volume modulated arc therapy included 50.4 Gy in 28 fractions to the pelvis and 59.4 Gy simultaneous boost in 28 fractions to involved pelvic and para-aortic lymph nodes, and subsequent high-dose-rate intracavitary brachytherapy at a total dose of 30.0 Gy in 5 fractions, twice a week. Concurrent chemotherapy regimen included weekly cisplatin (40 mg/m2) and weekly nab-paclitaxel at escalating doses (10, 20, 33, 50, and 70 mg/m2 per week). Duration of the planned treatment was 8 weeks. Grade 4 hematologic toxicity and grade 3 or above nonhematologic toxicity were considered as DLT. MTD was defined as the highest dose with ≤33% DLT. A total of 22 patients were enrolled from September 2019 to August 2021. The most common adverse events were grade 1 to 3 leukopenia, diarrhea, and nausea/vomiting. A total of 4 patients (18.0%) experienced DLT: grade 3 hypokalemia at 33 mg/m2 (1 of 6 subjects), grade 3 deep vein thrombosis at 50 mg/m2 (1 of 6) and 70 mg/m2 (1 of 4), and grade 3 perineum edema at 70 mg/m2 (1 of 3). The estimated MTD was 50 mg/m2. Complete response was observed in 20 patients (90.9%). In patients undergoing concurrent IG-VAMT with nab-paclitaxel plus cisplatin for LACC, MTD of nab-paclitaxel was 50 mg/m2. Complete response rate was 90.9%.


Dissatisfaction encodes a tailless-like nuclear receptor expressed in a subset of CNS neurons controlling Drosophila sexual behavior.
The dissatisfaction (dsf) gene is necessary for appropriate sexual behavior and sex-specific neural development in both sexes. dsf males are bisexual and mate poorly, while mutant females resist male courtship and fail to lay eggs. Males and females have sex-specific neural abnormalities. We have cloned dsf and rescued both behavioral and neural phenotypes. dsf encodes a nuclear receptor closely related to the vertebrate Tailless proteins and is expressed in both sexes in an extremely limited set of neurons in regions of the brain potentially involved in sexual behavior. Expression of a female transformer cDNA under the control of a dsf enhancer in males leads to dsf-like bisexual behavior.


Pneumoperitoneum following hernia repair.
In a small series of 20 consecutive patients it proved impossible, using conventional radiography, to detect free intraperitoneal air following herniorrhaphy.


(τ 1,τ 2)δ-semicontinuous multifunctions.
The purpose of the present article is to introduce the concepts of upper and lower ( τ 1 , τ 2 ) δ -semicontinuous multifunctions. Some characterizations of upper and lower ( τ 1 , τ 2 ) δ -semicontinuous multifunctions are investigated. The relationships between upper and lower ( τ 1 , τ 2 ) δ -semicontinuous multifunctions and the other types of continuity for multifunctions are established.


Repair of DNA interstrand crosslinks may take place at the nuclear matrix.
Host cell reactivation assay using Trioxsalen-crosslinked plasmid pEGFP-N1 showed that human cells were able to repair Trioxsalen interstrand crosslinks (ICL). To study the mechanism of this repair pathway, cells were transfected with the plasmids pEGFP-1, which did not contain the promoter of the egfp gene, and with pEGFP-G-, which did not contain the egfp gene. Neither of these plasmids alone was able to express the green fluorescent protein. After cotransfection with the two plasmids, 1%-2% of the cells developed fluorescent signal, which showed that recombination events had taken place in these cells to create DNA constructs containing the promoter and the gene properly aligned. When one or both of the plasmids were crosslinked with Trioxsalen, the recombination rate increased several fold. To identify the nuclear compartment where recombination takes place, cells were transfected with crosslinked pEGFP-N1 and the amount of plasmid DNA in the different nuclear fractions was determined. The results showed that Trioxsalen crosslinking increased the percentage of matrix attached plasmid DNA in a dose-dependent way. Immunoblotting experiments showed that after transfection with Trioxsalen crosslinked plasmids the homologous recombination protein Rad51 also associated with the nuclear matrix fraction. These studies provide a model system for investigating the precise molecular mechanisms that appear to couple repair of DNA ICL with nuclear matrix attachment.


Characterisation of the polysaccharide produced by Acetobacter xylinum strain CR1/4 by light scattering and atomic force microscopy.
The molecular weight of the extracellular polysaccharide (CR1/4) produced by Acetobacter xylinum strain CR1/4 has been shown to be dependent upon growth conditions. Under normal growth conditions a high molecular weight polysaccharide ( > 1 x 10(6) Da) is produced. Maintaining the pH at 5 results in an order of magnitude increase in the total yield of polysaccharide, but also an order of magnitude decrease in molecular weight. Analysis of the CR1/4 polysaccharides by the techniques of atomic force microscopy and static light scattering suggests that they are double helices. In solution the molecules behave as stiff coils with a Kuhn statistical segment length of 325 nm.


Longitudinal Analysis of Retinal Ganglion Cell Damage at Individual Axon Bundle Level in Mice Using Visible-Light Optical Coherence Tomography Fibergraphy.
We developed a new analytic tool based on visible-light optical coherence tomography fibergraphy (vis-OCTF) to longitudinally track individual axon bundle transformation as a new in vivo biomarker for retinal ganglion cell (RGC) damage. After acute optic nerve crush injury (ONC) in mice, we analyzed four parameters: lateral bundle width, axial bundle height, cross-sectional area, and the shape of individual bundles. We next correlated the morphological changes in RGC axon bundles with RGC soma loss. We showed that axon bundles became wider and taller at three days post ONC (pONC), which correlated with about 15% RGC soma loss. At six days pONC, axon bundles showed a significant reduction in lateral width and cross-sectional area, followed by a reduction in bundle height at nine days pONC. Bundle shrinking at nine days pONC correlated with about 68% RGC soma loss. Both experimental and simulated results suggested that the cross-sectional area of individual RGC axon bundles is more sensitive than bundle width and height to indicate RGC soma loss. This study is the first to track and quantify individual RGC axon bundles in vivo after ONC injury. Recognizing RGC loss at its earliest stage is crucial for disease diagnosis and treatment. However, current clinical methods to detect the functional and structural changes in the inner retina are not sensitive enough to directly assess RGC health. In this study, we developed vis-OCTF-based parameters to track RGC damage, making possible to establishing a quantifiable biomarker for glaucoma.


[Changes in arterial blood flow patterns by patients' posture during hepatic arterial infusion chemotherapy assessed by 99mTc-MAA perfusion scintigraphy].
Hepatic arterial perfusion scintigraphy (HAPS) with 99mTc-macroaggregated albumin (MAA) was performed to reveal the effect of patients' posture for the arterial blood flow patterns in hepatic arterial infusion (HAI) chemotherapy. 20 patients of liver metastases with the percutaneously implanted catheter into the hepatic artery underwent HAPS following administration of 99mTc-MAA at the supine and the upright position under one week interval. 10 ml of the saline with radionuclide was injected at a rate of 1 ml per minute. Acquired two images at the different position of each patient were compared and grouped into three classes; similar, slightly different and different. Of 20 patients, 6 (30%) were judged as similar, 8 (40%) as slightly different, and 6 (30%) as different. These results suggest that the drug distribution can change by patients' posture in case of the slow rate HAI performed with continuous infusion pump.


Pathways to improve early intervention for eating disorders: Findings from a systematic review and meta-analysis.
Treatment-seeking rates among eating disorder (ED) populations are relatively low, with only one in four individuals seeking help. Previous research has identified many factors that might be associated with help-seeking in EDs, but to date no review has investigated the quantitative association between these factors and actual help-seeking behavior. The aim of the current review was to synthesize the relevant quantitative literature on factors (i.e., perceived barriers, characteristics associated with treatment seeking, demographic variables) associated with help-seeking using meta-analytic strategies, as well as provide recommendations on future early intervention research strategies to promote early help-seeking. Overall, 19 studies were included, identifying 141 perceived barriers (e.g., stigma) or individual characteristics (e.g., BMI, duration of illness) and 56 demographic variables (e.g., ethnicity), which were synthesized into 24 unique variables. Less help-seeking was predicted by higher levels of denial and less perceived ability of others to provide help. Given the small number of studies these results should be considered preliminary. Future studies should consider barriers to help-seeking when creating early intervention approaches. To improve help-seeking rates we suggest the use of targeted psychoeducational materials and co-design with people with lived experience when developing new strategies. The present study addresses a significant gap in the literature by synthesizing factors associated with help-seeking, with the aim of informing early intervention strategies to promote early help-seeking in eating disorder populations. Denial of illness and perceived inability of others to provide help were associated with lower help-seeking. Future studies should consider barriers to help-seeking and co-design with people with lived experience when creating new early intervention strategies.


Linoelaidic acid enhances adipogenic differentiation in adipose tissue-derived stromal cells through suppression of Wnt/β-catenin signaling pathway in vitro.
Obesity has become a major health problem which is related with high-trans fatty acids diet. Adipogenic differentiation of adipose tissue-derived stromal cells (ADSCs) plays an important role in the development of adipose tissue. In order to determine the effect of trans fatty acids on adipogenic differentiation in ADSCs, cells were treated with linoelaidic acid, as well as linoleic acid and linolenic acid. We found that linoelaidic acid significantly increased the lipid droplet formation and triglyceride content compared with linoleic acid and linolenic acid. Linoelaidic acid also down-regulated the levels of β-catenin in cells and inhibited the accumulation of β-catenin in cell nuclei. Lithium chloride, an activator of Wnt/β-catenin pathway, antagonized the enhancement of linoelaidic acid on adipogenesis and up-regulated the levels of β-catenin in ADSCs. These results indicated that linoelaidic acid could enhance the adipogenic differentiation in ADSCs in vitro, which is partly due to the suppression of Wnt/β-catenin pathway.


Effect of gamma interferon preparations on in vitro phagocytosis and degradation of Escherichia coli by mouse peritoneal macrophages.
Treatment of mouse peritoneal macrophages by gamma (type II, immune) interferon depressed the ingestion of non-opsonized Escherichia coli mediated by the non specific receptor, and also the intracellular degradation of the ingested bacteria. These effects were time and dose-dependent, and sensitive for trypsin and pH 2 treatment. The intracellular concentration of three lysozomal enzymes, beta-glucuronidase, acid phosphatase and cathepsin D, was elevated in gamma interferon-treated macrophages.


The effects of preweaning manganese exposure on spatial learning ability and p-CaMKIIα level in the hippocampus.
The effects and mechanisms of preweaning Manganese (Mn) exposure on cognitive dysfunction remain unclear. This study evaluated the effects of preweaning Mn exposure on spatial learning and memory as well as the protein expression of CaMKIIα and p-CaMKIIα. We treated neonate rats with Mn(2+) doses of 0 (control group), 10, 20 and 30mg of Mn(2+) per kg body weight (Mn-exposed groups) over postnatal day (PND) 1-21 by intraperitoneal injection. The ability of spatial learning and memory was tested on PND 22 using the Morris water maze (MWM), while the protein expressions of CaMKIIα and p-CaMKIIα in the hippocampus were evaluated by Western blotting. The levels of Mn in the blood and hippocampus were measured by inductively coupled plasma-mass spectrometry (ICP-MS). The rats in Mn-exposed groups showed a significant delay in spatial learning ability on the third day of the MWM without dose-dependent differences, but there was no effect on the spatial memory ability. p-CaMKIIα, but not CaMKIIα protein expression significantly reduced in the Mn-exposed group. These findings suggested that the inhibition of p-CaMKIIα could be one of the mechanisms involved in the occurrence of Mn-induced cognitive impairments.


Production of 2,3-butanediol from acid hydrolysates of Jatropha hulls with Klebsiella oxytoca.
Jatropha hulls were successfully for the first time used as raw materials for the production of 2,3-butanediol via dilute sulfuric acid hydrolysis and fermentation with Klebsiella oxytoca. Two-step hydrolysis was used to effectively hydrolyze the hulls at 150°C after pretreatment. In the first-step, hemicellulose was hydrolyzed under mild conditions (0.5h, 1.5% acid) to avoid secondary decomposition. The remained cellulose was further hydrolyzed in the second-step under severer conditions (1h, 4% acid). After hydrolysis, total hydrolysis yield was 64%, which was much higher than that (37%) from the first-step. Maximum yields of 2,3-butanediol and acetoin in flask experiments were 35.6% and 41.4% from the hydrolysates of the first- and second-step hydrolysis, equivalent to 71.2% and 82.8% of the theoretical values, respectively. Similar yields were obtained in a controlled bioreactor but with higher productivities. Jatropha hulls are attractive raw materials for the production of 2,3-butanediol with high yield.


Delirium in the acute care setting: characteristics, diagnosis and treatment.
Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances. It is also the most common psychiatric syndrome found in the general hospital setting, its prevalence surpassing better known psychiatric disorders. This article reviews the published literature on delirium and addresses the epidemiology, known etiologic factors, presentation and characteristics of delirium, while emphasizing what is known about treatment strategies and prevention. Given increasing evidence that delirium is not always reversible and the many sequelae associated with its development, physicians must do everything possible to prevent its occurrence or shorten its duration, by recognizing its symptoms early, correcting underlying contributing causes, and using treatment strategies proven to help recover functional status.


Differentiation of human malignant melanoma cells that escape apoptosis after treatment with 9-nitrocamptothecin in vitro.
After in-vitro exposure to 0.05 micromol/L 9-nitrocamptothecin (9NC) for periods of time longer than 5 days, 65% to 80% of the human malignant melanoma SB1B cells die by apoptosis, whereas the remaining cells are arrested at the G2-phase of the cell cycle. Upon discontinuation of exposure to 9NC the G2-arrested cells resume cell cycling or remain arrested depending on the duration of 9NC exposure. In contrast to cycling malignant cells, the cells irreversibly arrested at G2 exhibit features of normal-like cells, the melanocytes, as assessed by the appearance of dendrite-like structures; loss of proliferative activity; synthesis of the characteristic pigment, melanin; and, particularly, loss of tumorigenic ability after xenografting in immunodeficient mice. Further, the expression of the cyclin-dependent kinase inhibitor p16 is upregulated in the 9NC-treated, G2-arrested, but downregulated in density G1-arrested cells, whereas the reverse is observed in the expression of another cyclin-dependent kinase inhibitor, p21. These results suggest that malignant melanoma SB1B cells that escape 9NC-induced death by apoptosis undergo differentiation toward nonmalignant, normal-like cells.


Early markers of kidney dysfunction and cognitive impairment among older adults.
Age-related decline in kidney function can be an important risk factor for cognitive impairment in older adults. In this study, we examined several kidney function measures for the association with cognitive function in older adults in hope to identify early and sensitive markers that can be used for the detection or screening for cognitive impairment. A total of 1982 older participants (aged ≥60years) in the 1999-2002 National Health and Nutrition Examination Survey was analyzed for the association between kidney function and cognitive impairment using multivariate logistic regression and general linear models. Cognitive functioning was assessed during the household interview using a version of the Digit Symbol Substitution Test of the Wechsler Adult Intelligence Scale III. In our study, participants with a score of <31, the 25th percentiles of the distribution, or who were unable to complete the sample exercise due to cognitive limitations were classified as having cognitive impairment. Of 1982 older adults, 503 were having cognitive impairment (weighted prevalence, 15.38%). Among the kidney function measures that we examined, the levels of serum cystatin C and urinary albumin were found being significantly associated with cognitive impairment after adjusting for age, sex, race/ethnicity, poverty status, education, physical activity, BMI, cigarette smoking, and alcohol consumption. Cognitive functioning scores were significantly decreasing with increasing levels of kidney dysfunction markers. Serum cystatin C and urinary albumin that are early markers of chronic kidney disease might serve as early and effective markers for cognitive decline in older adults. Mechanisms underlying the observed association need to be further characterized.


Outcomes and predictors of harmful relapse following liver transplantation for alcoholic liver disease in an Australian population.
Limited studies of patient survival and alcoholic relapse following transplantation for alcoholic liver disease have been described in Australian populations. To describe these outcomes in an Australian population, to determine the association between harmful alcoholic relapse and patient survival, and to examine pre-transplant variables associated with harmful relapse. Single centre, retrospective review of consecutive patients transplanted at the South Australian Liver Transplant Unit. Relapse was identified by an independent investigator using case note review and confidential patient questionnaire. A total of 87 patients (median age 52 years, 84% male, median Model for End-Stage Liver Disease (MELD) score 18) was included in the study with a median follow-up time of 50 months. The 1-, 3- and 5-year survival of patients was 93.1, 87.4 and 82.0% respectively. Two deaths were directly attributable to graft failure due to alcohol. Fourteen (16%) patients fulfilled criteria for harmful relapse and 18 (21%) patients experienced any form of relapse to alcohol. Harmful relapse was associated with increased mortality (hazard ratio (HR) 3.2, 95% confidence interval (CI) 1.1-9.7, P = 0.041). Only two factors were independently associated with harmful relapse on multivariate analysis; prior alcohol rehabilitation (HR 8.4, 95% CI 2.5-28.4, P = 0.001) and single versus married status (HR 0.09, 95% CI 0.02-1.2, P = 0.019). Good patient survival outcomes were seen for this South Australian population. Harmful alcohol relapse occurs in a minority of patients and rarely results in direct graft loss. Modifiable pre-transplant factors that predict harmful relapse were not identified.


Low frequency noise enhances cortisol among noise sensitive subjects during work performance.
Salivary free cortisol concentration, rated stress and annoyance were determined in 32 subjects before, during and after carrying out a battery of performance tasks for 2 hours during exposure to ventilation noise, with dominant low frequencies (low frequency noise) or a flat frequency spectrum (reference noise). Both noises had a level of 40 dBA. All subjects were studied on two occasions and were exposed to both noises in strict rotation. Subjects were categorised as high- or low-sensitive to noise in general and low frequency noise in particular on the basis of questionnaires. Cortisol concentrations during the task were not significantly modulated by the noises or related to noise sensitivity alone. The normal circadian decline in cortisol concentration was however significantly attenuated in subjects high-sensitive to noise in general, when they were exposed to the low frequency noise. This noise was rated as more annoying and more disruptive to working capacity than the reference noise. The study showed physiological evidence of increased stress related to noise sensitivity and noise exposure during work. This is the first study to demonstrate an effect of moderate levels of noise on neuroendocrine activity. The impact of long-term exposure to moderate noise levels, and particularly low frequency noise, in the workplace deserves further investigation.


AMBER force field implementation of the boronate function to simulate the inhibition of beta-lactamases by alkyl and aryl boronic acids.
Boronic acids are a very appealing class of serine proteases inhibitors whose rational design suffers, in spite of their therapeutic potential, from the lack of boron-related parameters in force fields commonly used for proteins. We introduced bonded, non-bonded and point charges in the MacroModel/Amber force field, as well as GB/SA solvation parameters, to model boronic acids as tetrahedral adducts formed after protease's serine Ogamma coordination. With the aim to check the implemented force field, flexible docking studies were performed on three crystallographic complexes of beta-lactamases with boronic acids that output the crystallographic conformation of the complexes as the global minimum energy structure. Although the used approach was basic, nevertheless the resultant force field seems to be efficient and suitable for the structure-based design of new boronic inhibitors of beta-lactamases.


Mechanisms of syncope in implantable cardioverter-defibrillator recipients who receive device therapies.
A significant proportion of implantable cardioverter defibrillator (ICD) recipients ultimately receive device therapies. Determinants and mechanisms of syncopal events in these patients are not established. To address this issue, we reviewed prospectively collected data on 114 ICD recipients who received device therapies. There were 99 men and 15 women with a mean age of 63+/-10 years. Ejection fraction was 29+/-13%. At initial presentation, 74 patients (65%) had syncope during arrhythmia. Of 114 patients, 18 patients (16%) subsequently experienced syncope during device therapies over a period of 35+/-24 months of follow-up. Arrhythmias during syncopal events documented by telemetry, event recorders, RR intervals, or ICD stored electrograms were obtainable in 13 patients, and included sustained monomorphic ventricular tachycardia (VT) in 10 patients, ventricular fibrillation (VF) in 2 patients, and atrial fibrillation in 1 patient. The explanations for arrhythmia-related syncope included ICD proarrhythmia in 8 patients (62%), rapid monomorphic VT in 3 (23%), and VF in 2 patients (15%). Patients with syncope could not be differentiated from those without syncope by demographic, clinical, or electrophysiologic variables. There was no significant difference in mortality between patients with or without syncope (39% vs 25%, p = 0.25). Syncope is not uncommon in ICD recipients who receive device therapies. When it occurs, syncope is often due to ICD proarrhythmia; hence, it is potentially preventable by meticulous device programming.


Phosphorylation of human choriogonadotropin. Stoichiometry and sites of phosphate incorporation.
Human chorionic gonadotropin (hCG) and its subunits were studied as substrates for cAMP-dependent protein kinase. Phosphorylated residues were identified in peptide fragments by sequence analysis following appropriate hydrolysis and purification. Only the free beta-subunit was phosphorylated. Intact beta subunit incorporated 1 mol of phosphate/mol of peptide. This was localized to Thr 97, within the sequence -Arg-Arg-Ser-Thr-, which resembles one type of acceptor site for cAMP-dependent phosphorylation. Since beta Thr 97 did not phosphorylate in native hCG, this residue may be masked by the alpha subunit. Reduced and carboxymethylated hCG beta phosphorylated to 2.8 mol of phosphate/mol of peptide. Besides Thr 97, phosphate was also found at Ser 66 and Ser 96. Ser 66 occurs within a segment recognized to be favored for phoshorylation with the general sequence -Arg-X-X-Arg-X-X-Ser-. The appearance of this site in the linearized peptide suggests that Ser 66 is "buried" in the native conformation of the beta subunit. Two synthetic peptides representing residues 93-102 of hCG beta were also examined. The disulfide form of the peptide phosphorylated at Thr 97 while the linear peptide phosphorylated at Ser 96. Conformation as well as primary structure can thus influence the site of phosphate incorporation.


Sex differences of small airway function and fractional exhaled nitric oxide in patients with mild asthma.
Sex differences of small airway function (SAF) and fractional exhaled nitric oxide (FeNO) in patients with mild asthma remain unclear. To evaluate sex differences of SAF and FeNO in patients with mild asthma confirmed by positive methacholine challenge test (MCT) result. This cross-sectional, double-centered, observational study enrolled 1609 adult patients with forced expiratory volume in 1 second greater than or equal to 80% and suspected asthma symptoms. Data of spirometry, FeNO, impulse oscillometry measurements, and peripheral blood test result were compared between males and females. The receiver-operating characteristic curves of SAF parameters and FeNO in predicting positive MCT result were also calculated. In patients with mild asthma matched by age, males had better SAF but higher FeNO levels than females (60 [29.27%] vs 187 [46.75%] for small airway dysfunction, 78.6% vs 72.0% for forced expiratory flow [FEF]50%, 67.5% vs 60.1% for FEF75%, 73.7% vs 67.4% for FEF25%-75%, and 42.0 ppb vs 29.0 ppb for FeNO, respectively, all P ≤ .001). The FeNO levels in male current smokers were considerably lower than those of nonsmokers. SAF and FeNO values declined more rapidly with age among female than male patients with asthma. The optimal cutoff values of FEF25%-75%, FEF50%, and FeNO for predicting a positive MCT result were 81.5%, 86.4%, and 41.0 ppb in males vs 73.7%, 76.9%, and 35.0 ppb in females. In patients with mild asthma, the female patients have worse SAF, lower FeNO levels, and a more prominent decline trend of those parameters with age than males. Sex-specific cutoff values should be considered when SAF parameters (FEF25%-75%, FEF50%), alone or combined with FeNO, are used to predict positive MCT result in asthma diagnosis.


The diagnostic value of 123I-IMP SPECT in ocular adnexal lymphoma.
N-isopropyl- (123I) p-iodoamphetamine (123I-IMP) is specifically accumulated in primary central nervous system lymphoma (PCNSL) during single-photon emission tomography (SPECT) and contributes to its diagnostic imaging. However, whether 123I-IMP is accumulated in ocular adnexal lymphoma (OAL), one of the malignant intraorbital tumors, remains unclear. This study aimed to evaluate the diagnostic value of 123I-IMP SPECT in OAL. Between August 2005 and June 2020, 26 patients with intraorbital tumors underwent neurosurgery at the tertiary care center. Of these, 15 patients who underwent 123I-IMPSPECT before surgery were retrospectively examined. The region of interest was set in the cerebellum ipsilateral to the intraorbital tumor on 123I-IMP SPECT, and the tumor-to-cerebellum ratio (T/C ratio) was calculated using the following formula: T/C ratio = [accumulation of tumor (count/pixel)]/[accumulation of ipsilateral normal cerebellar hemisphere (count/pixel)]. Six patients were included in the OAL group, who were pathologically diagnosed with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), diffuse large B-cell lymphoma (DLBCL), and plasmacytoma. The T/C ratio in the OAL group was statistically higher than that in the non-OAL group (p < 0.01). The optimal cutoff values for both groups were between 0.76 and < 0.93. The sensitivity and specificity were 1.00, respectively. 123I-IMP SPECT is useful as one of the examinations in the differential diagnoses of OAL, because it showed a significantly higher accumulation in OAL group than in non-OAL group.


Annulate lamellae in erythroblasts in the mice splenic colonies.
Lethally irradiated mice received a transfusion of normal bone marrow cells from the same strain mice. The transfused colony-forming cells (stem cells) were settled in the spleen of the recipient and proliferated in it into erythroblast colonies. Some of these mice were given chloramphenicol or thiamphenicol for 7 days after marrow cell transfusion. Annulate lamellae were frequently observed exclusively in the erythroblasts of the mice received a injection of thiamphenicol.


BMI trajectories and risk of overall and grade-specific prostate cancer: An observational cohort study among men seen for prostatic conditions.
Dynamic longitudinal patterns in body mass index (BMI) have been suggested to better predict health outcomes than static measures. Effects of BMI trajectories on prostate cancer (PCa) risk have not been thoroughly explored. Cohort data were derived from electronic medical records of patients who were admitted to a tertiary-care hospital in the Southeastern USA during 1994-2016. Patients with a history of urologic clinic visit because of any prostatic condition and with repeatedly measured BMI (n = 4857) were included. BMI trajectories prior to PCa diagnosis were assessed using the developmental trajectory analysis method. Cox proportional hazards regression modeling was used to estimate adjusted hazard ratio (aHR) with 95% confidence intervals (CIs) for overall and grade-specific PCa. The median age (interquartile range, IQR) of the participants at baseline was 63 (54, 72) years. Over a median follow-up (IQR) of 8.0 (2.0, 13.0) years, 714 (14.7%, 714/4857) were diagnosed with PCa. Men with growing BMI trajectory progressing from normal weight to overweight/obese had a 76% increased PCa risk (aHR = 1.76; 95% CI: 1.25, 2.48), and men being obese and experiencing progressive weight gain had 3.72-fold increased PCa risk (aHR = 3.72; 95% CI: 1.60, 8.66), compared to men with persistently normal BMI. The associations were more pronounced for PCa with Gleason score ≥7. No significant association of decreasing BMI trajectory progressing from obese to normal BMI was found with PCa risk. Progressively body weight gain during middle-to-late adulthood was associated with increased PCa risk for both normal weight and overweight men. Further studies are warranted to confirm this finding.


Effect of methyldopa and isradipine on fetal heart rate pattern assessed by computerized cardiotocography in human pregnancy.
The effects of two antihypertensive drugs, methyldopa and isradipine, on fetal heart rate pattern were analyzed by computerized cardiotocography. The first part of the study was a prospective, randomized, controlled trial of 19 women with preeclampsia in the third trimester given 2.5 mg of oral slow-release isradipine twice a day or 250 mg of methyldopa three times a day. In a second part of the study 23 women with preeclampsia in the third trimester given 5 mg of oral slow-release isradipine twice a day were compared with 23 matched controls without medication. Main outcome measures were maternal blood pressure and mean baseline fetal heart rate, fetal movements, number of accelerations, periods of high and low baseline variability, and mean baseline heart rate variability. Compared with the pretreatment value, the mean arterial blood pressure decreased significantly in all drug treatment groups. Fetal heart rate characteristics were not significantly changed during drug treatment or bed rest. The various features of the fetal heart rate pattern evaluated by computerized methods were not influenced by treatment with methyldopa or isradipine.


Improved Oxygenation After Transport in Patients With Hypoxemic Respiratory Failure.
The purpose of this study is to measure the rate and magnitude of changes in oxygenation that occur in patients with hypoxemic respiratory failure after transport by a critical care transport team. We performed a retrospective review of 239 transports of patients with hypoxemic respiratory failure requiring a fraction of inspired oxygen (Fio2) > 50% transported from October 2009 to December 2012 from referring hospitals to 3 tertiary care hospitals. We analyzed the change the ratio of the partial pressure of oxygen in the blood to FiO2 from the sending to the receiving hospital as well as the percentage saturation of oxygen (Spo2) before, after, and en route. The mean change in the Pao2/Fio2 ratio from the sending to the receiving hospital was an increase of 27.62 (95% confidence interval [CI], 15.84-39.40; P = .0003). The mean change in Pao2 was an increase of 27.85 mm Hg (CI, 17.49-38.22; P < .0001). The mean Spo2 was not significantly changed at -0.12 (CI, - 1.69 to 1.45, P = .9). Despite improvement in the Pao2/Fio2 ratio and a stable Spo2 on arrival, 28.1% of patients desaturated to Spo2 < 90% in transport. In patients with hypoxemic respiratory failure, Pao2/Fio2 and Pao2 increased after transport by a critical care transport team despite 28.1% of patients desaturating with hypoxemia in transit.


Lower prednisone dosing for steroid-sensitive nephrotic syndrome relapse: a prospective randomized pilot study.
Relapses of steroid-sensitive nephrotic syndrome are traditionally treated with prednisone 2 mg/kg/day or 60 mg/m2/day. Retrospective data support the use of lower doses. We designed a prospective randomized pilot study to investigate the efficacy of different doses in achieving remission of steroid sensitive nephrotic syndrome relapse. The cohort included 30 children with relapsed steroid sensitive nephrotic syndrome, mean age 6.3 ± 3 years and mean disease duration 2.2 ± 1.8 years. The children were randomized to receive 2, 1.5, or 1 mg/kg/day prednisone. The corresponding times to response, defined as the first of 3 consecutive days without proteinuria, were 7.2 ± 1.4, 10.2 ± 5.1, and 9 ± 3.3 days; the difference between the 1.5 and 2 mg/kg/day groups was statistically significant. One patient each in the 1 mg/kg/day and the 1.5 mg/kg/day groups failed to respond and were switched to 2 mg/kg/day, leading to a response after 3 and 10 days, respectively. Mean cumulative prednisone doses in the 3 groups were 45.5 ± 3.4, 42.7 ± 25.9, and 24.9 ± 7.4 mg/kg, respectively (P < 0.05).Conclusion: In the present study, treatment of childhood steroid sensitive nephrotic syndrome relapse with prednisone 1-1.5 mg/kg/day led to a significantly lower cumulative dose than the standard dose. Treatment with a lower dose may be equally safe and effective to the standard dose.What is Known:• Relapses of steroid-sensitive nephrotic syndrome are traditionally treated with standard-dose steroids.• Treatment with corticosteroids may have significant adverse effects mainly with long-term use.What is New:• Treatment of steroid sensitive nephrotic syndrome relapse with 1-1.5 mg/kg/day prednisone may lead to a significantly lower cumulative dose.• Treatment with a lower steroid dose may be as effective as the standard dose in achieving remission of steroid sensitive nephrotic syndrome relapse.


Acceleration of biodiesel-glycerol decantation through NaCl-assisted gravitational settling: a strategy to economize biodiesel production.
When making biodiesel, slow separation of glycerol; the main by-product of the transesterification reaction, could lead to longer operating times, bigger equipment and larger amount of steel and consequently increased production cost. Therefore, acceleration of glycerol/biodiesel decantation could play an important role in the overall biodiesel refinery process. In this work, NaCl-assisted gravitational settling was considered as an economizing strategy. The results obtained indicated that the addition of conventional NaCl salt decreased the glycerol settling time significantly up to more than five times. However, NaCl inclusion rates of more than 3g to the mixture (i.e. 5 and 10 g) resulted in significantly less methyl ester purity due to the occurrence of miniemulsion phenomenon. Overall, addition of 1g NaCl/100 ml glycerol-biodiesel mixture was found as optimal by accelerating the decantation process by 100% while maintaining the methyl ester purity as high as the control (0 g NaCl).


Combined effects of different food rations and sublethal copper exposure on growth and energy metabolism in common carp.
Common carp (Cyprinus carpio) were fed two different rations, 0.5% body weight (low ration; LR) and 5% body weight (high ration; HR), throughout acclimation, sublethal (64 microg/L) Cu exposure for 28 days, and a subsequent 2-week recovery period. Growth, liver water content, and liver energy stores were assessed during this period. Growth rates were elevated in HR fish compared to LR fish, as was the hepatic lipid content. This was associated with a higher water content in the livers of LR fish. Liver glycogen levels were similar in both feeding treatments and remained relatively stable during Cu exposure. Cu exposure caused a significant reduction in growth in both HR and LR fish. Reduction in growth coincided with significant changes in liver and blood composition. Liver lipid levels dropped significantly during the first days of the exposure in both feeding treatments, and the difference between LR and HR lipid levels disappeared during Cu exposure. During the first week of Cu exposure, the difference in liver water content disappeared as well, with a significant reduction of the water levels in the LR fish. A rise of hepatic protein was observed after 2 and 4 weeks of Cu exposure in the LR carp and after 4 weeks of exposure in the HR fish. Cu exposure led to pronounced increases in plasma ammonia concentrations in HR carp. Growth and energy stores recuperated during the 2-week recovery period in both feeding treatments. The observed changes during Cu exposure are probably related to physiological disturbances like hypoxia and stress, as well as an inhibition of ammonia excretion.


Transitional cell carcinoma of the ureter and renal pelvis.
Transitional cell carcinoma (TCC) of ureter and renal pelvis is relatively uncommon. Smoking, occupational carcinogens, analgesic abuse, Balkan nephropathy are the risk factors. Cytogenetic studies revealed that the most frequent aberration is the partial or complete loss of chromosome 9. Approximately 20-50% of patients with upper urinary tract (UUT) TCC have bladder cancer at some point on their course, whereas the incidence of UUT TCC after primary bladder cancer is 0.7-4%. Excretory urography and retrograde pyelography are the conventional diagnostic tools; however, ureteropyeloscopy combined with cytology and biopsy is more accurate. Grade and stage of the disease have the most significant impact on survival. Nephroureterectomy with bladder cuff excision has been the mainstay of treatment. Local resection may be appropriate for distal ureteral lesions especially when the disease is low grade and stage. Advances in endourology have made it possible to treat many tumors conservatively. Ureteroscopic and to a certain extent percutaneous surgical approaches are widely used today especially in patients with low grade, low stage disease. Endoscopic close surveillance is mandatory for these patients. Adjuvant topical therapies appear to be safe but confirmation of any benefits awaits the results of further large studies. More recently, laparoscopic techniques have become a viable alternative to open surgery, but long term cancer control data are lacking. Aggressive surgical resection does not affect the outcome of patients with advanced disease. Adjuvant radiotherapy is ineffective, and systemic chemotherapy results in a low complete response rate for patients with metastases.


Identifying barriers to the use of research faced by public health physicians in Norway and developing an intervention to reduce them.
To explore why public health physicians seldom use research-based information and to develop an intervention to remedy this on the basis of this study, other research literature and suitable theories of information-seeking and professional behaviour change. A qualitative study was conducted using focus groups, observation of individuals and interviews. The setting was Norwegian public health practice; 52 public health physicians from all over Norway participated in the study. We identified several barriers to the use of scientific literature that could be categorised as: psychological variables; environmental variables; and source characteristics. We developed an intervention that attempts to address these barriers, informed by previous research on the effectiveness of interventions to change professional practice and incorporating elements from social cognitive theories and the theory of innovation diffusion. The Norweigian public health physician works in an isolated environment which does not facilitate searching or obtaining scientific information, which does not ask for this information and far less encourages its use as a basis for decision-making. An intervention tailored to reduce some of the barriers to research use may lead to more frequent and extensive use of such information in public health decision-making.


The paediatric version of Wisconsin gait scale, adaptation for children with hemiplegic cerebral palsy: a prospective observational study.
In clinical practice there is a need for a specific scale enabling detailed and multifactorial assessment of gait in children with spastic hemiplegic cerebral palsy. The practical value of the present study is linked with the attempts to find a new, affordable, easy-to-use tool for gait assessment in children with spastic hemiplegic cerebral palsy. The objective of the study is to evaluate the Wisconsin Gait Scale (WGS) in terms of its inter- and intra-rater reliability in observational assessment of walking in children with hemiplegic cerebral palsy. The study was conducted in a group of 34 patients with hemiplegic cerebral palsy. At the first stage, the original version of the ordinal WGS was used. The WGS, consisting of four subscales, evaluates fourteen gait parameters which can be observed during consecutive gait phases. At the second stage, a modification was introduced in the kinematics description of the knee and weight shift, in relation to the original scale. The same video recordings were rescored using the new, paediatric version of the WGS. Three independent examiners performed the assessment twice. Inter and intra-observer reliability of the modified WGS were determined. The findings show very high inter- and intra-observer reliability of the modified WGS. This was reflected by a lack of systematically oriented differences between the repeated measurements, very high value of Spearman's rank correlation coefficient 0.9 ≤ |R| < 1, very high value of ICC > 0.9, and low value of CV < 2.5% for the specific physical therapists. The new, ordinal, paediatric version of WGS, proposed by the authors, seems to be useful as an additional tool that can be used in qualitative observational gait assessment of children with spastic hemiplegic cerebral palsy. Practical dimension of the study lies in the fact that it proposes a simple, easy-to-use tool for a global gait assessment in children with spastic hemiplegic cerebral palsy. However, further research is needed to validate the modified WGS by comparing it to other observational scales and objective 3-dimensional spatiotemporal and kinematic gait parameters. anzctr.org.au , ID: ACTRN12617000436370 . Registered 24 March 2017.


Discrimination and calibration of mortality risk prediction models in interventional cardiology.
Using a local percutaneous coronary intervention (PCI) data repository, we sought to compare the performance of a number of local and well-known mortality models with respect to discrimination and calibration. Accurate risk prediction is important for a number of reasons including physician decision support, quality of care assessment, and patient education. Current evidence on the value of applying PCI risk models to individual cases drawn from a different population is controversial. Data were collected from January 01, 2002 to September 30, 2004 on 5216 consecutive percutaneous coronary interventions at Brigham and Women's Hospital (Boston, MA). Logistic regression was used to create a local risk model for in-hospital mortality in these procedures, and a number of statistical methods were used to compare the discrimination and calibration of this new and old local risk models, as well as the Northern New England Cooperative Group, New York State (1992 and 1997), University of Michigan consortium, American College of Cardiology-National Cardiovascular Data Registry, and The Cleveland Clinic Foundation risk prediction models. Areas under the ROC (AUC) curves were used to evaluate discrimination, and the Hosmer-Lemeshow (HL) goodness-of-fit test and calibration curves assessed applicability of the models to individual cases. Multivariate risk factors included in the newly constructed local model were: age, prior intervention, diabetes, unstable angina, salvage versus elective procedure, cardiogenic shock, acute myocardial infarction (AMI), and left anterior descending artery intervention. The area under the ROC curve (AUC) was 0.929 (SE=0.017), and the p value for the Hosmer-Lemeshow (HL) goodness-of-fit was 0.473. This indicates good discrimination and calibration. Bootstrap re-sampling indicated AUC stability. Evaluation of the external models showed an AUC range from 0.82 to 0.90 indicating good discrimination across all models, but poor calibration (HL p value < or = 0.0001). Validation of AUC values across all models suggests that certain risk factors have remained important over the last decade. However, the lack of calibration suggests that small changes in patient populations and data collection methods quickly reduce the accuracy of patient level estimations over time. Possible solutions to this problem involve either recalibration of models using local data or development of new local models.


Concordance of distinguishing electrocardiographic features during sinus rhythm with the location of accessory pathways in the Wolff-Parkinson-White syndrome.
Knowledge of the location of accessory pathways in patients with Wolff-Parkinson-White (WPW) syndrome is pertinent to patient management. Despite the recognition that features of delta waves present during maximal preexcitation reflect ventricular activation at different sites around the anulus fibrosus, the value of electrocardiographic patterns observed during sinus rhythm, when ventricular preexcitation is often not maximal for identifying accessory pathway locations, has not been determined. In this study, 12-lead electrocardiograms recorded during sinus rhythm from 66 patients with WPW syndrome were analyzed for delta-wave polarity, QRS axis in the frontal plane, the pattern of precordial R-wave transition, and concordance between electrocardiographic patterns and the site of the accessory pathway determined using catheter and intraoperative computer mapping. Electrocardiograms from patients with left lateral sites showed negative delta waves in leads I or aVL, a normal QRS axis and early precordial R-wave transition (20 of 24 patients); left posterior sites manifested negative delta waves in II, III and aVF and a prominent R wave in V1 (14 of 16 patients); posteroseptal sites had negative delta waves in II, III and aVF, a superior QRS axis and an R less than S in V1 (all 16 patients); right free wall locations manifested negative delta waves in aVR, a normal QRS axis, and R-wave transition in V3-V5 (6 of 6 patients); and anterior septal sites had negative delta waves in V1 and V2, a normal QRS axis, and R-wave transition in V3-V5 (4 of 4 patients). Characteristic electrocardiographic patterns were not observed in 5 patients because of insufficient preexcitation. Each had a left lateral or left posterior pathway. Overall, the proposed electrocardiographic criteria derived during sinus rhythm identified correctly the accessory pathway location in 60 of 66 patients (91%). Thus, the electrocardiogram provides the physician with a reliable noninvasive means of regionalizing the location of accessory pathways in patients with WPW syndrome.


Mandible reconstruction using a vascularized fibula flap from a post-polio paralytic limb.
The case of 69-year-old man with a post-polio paralytic limb who was diagnosed with carcinoma of the lower alveolus is presented. A successful mandible reconstruction was performed using a vascularized fibula osteocutaneous flap harvested from the polio-affected limb. The skin perfusion and quality of the bone were good. The donor defect healed uneventfully. Harvesting the flap from the polio-affected limb also significantly reduced the donor site morbidity. This case is novel in presenting the successful use of a free fibula flap harvested from a leg affected by paralytic poliomyelitis.


Postoperative apnea in preterm infants.
Preterm infants may become apneic during the immediate post-operative period. To define this risk, the authors studied prospectively the breathing patterns of 47 preterm infants less than 60 weeks postconception with pneumocardiograms before and after general inhalational anesthesia. Eighteen infants (37%) had prolonged apnea (greater than 15 s) postoperatively, and an additional seven infants (14%) had short apnea (6-15 s) postoperatively. An infant's risk of prolonged and short postoperative apnea was related to a young postconceptional age (P less than 0.05) and to a history of necrotizing enterocolitis (P less than 0.01). Furthermore, as the postconceptional age of the infant increased, the risk of postoperative apnea decreased proportionately (P less than 0.025). Among the 18 infants with prolonged apnea, 83% experienced multiple apneic episodes. Manual stimulation was required in order for breathing to return in 13 (72%) of the infants. Breathing resumed spontaneously in four (22%) of the infants, and one infant required mechanical ventilation due to repeated prolonged apnea. The first apneic event occurred within 2 h postoperatively in 13 of the infants (72%); the remaining five infants (28%) had their initial apneic episode as late as 12 h after operation. The postoperative time to the last prolonged apneic event was inversely related to the postconceptional age (P less than 0.01, r = -0.70) and extended up to 48 h postoperatively. The preoperative pneumocardiogram was not a reliable test for predicting postoperative apnea (sensitivity 56%, specificity 83%).(ABSTRACT TRUNCATED AT 250 WORDS)


Recognition of viral antigens in 6/94 virus-induced T-cell-mediated cytotoxicity.
Distinct events in the virus-stimulated T-cell-mediated cytotoxicity (V-CMC) have been investigated: 1.) The induction of V-CMC is possible by immunizing mice with infectious as well as UV-inactivated virus (parainfluenza type 1 strain 6/94), or with virus-infected cells either compatible or imcompatible with the recipient. 2). Recognition of viral antigens by the effector cells occurs independently of the H2 environment: Fractionation of effector cells on columns loaded with virus-infected cells eliminates virus-specific cytotoxic cells. Effector cells and cells on the column need not share H-2 antigens. The findings are discussed with regard to the H2 restriction of the virus induced T-cells mediated cytotoxicity.


Regional variation in travel to health services following transport-related major trauma.
Post-discharge healthcare needs are complex and persistent for people following major trauma. A number of geographic barriers to accessing healthcare exist, particularly for people in regional areas. The aim of this study was to explore regional variation in the distances travelled to access health services and identify patterns of health service use in the first three years following transport-related major trauma. This registry-based cohort study used linked data from the Victorian State Trauma Registry (VSTR) and the Transport Accident Commission (TAC). Victorians who sustained major trauma from a transport-related event between January 1 2006 and December 31 2016, with at least three years of follow-up TAC claims data were included in the study. Geospatial mapping of the median distance travelled to medical and allied health services was conducted for each Victorian Local Government Area. In the first three years post-discharge, 4,964 people (75.6%) visited a general practitioner, 5058 (77.0%) saw other medical professionals, 2269 (34.6%) accessed mental health services, 2154 (32.8%) saw an occupational therapist and 4404 (67.0%) attended a physical therapy service. Geospatial mapping revealed that people in regional Local Government Area travelled further distances to access health services. Specific clustering of increased travel distances was observed in regional areas of the far west and north-east of Victoria. The number of people using services declined with each subsequent year beyond hospital discharge. However, the number of trips were consistent over time for those still engaged in services. Distances travelled to access health services vary across geographic regions and may result in an increased travel burden for those in some regional Local Government Area. Understanding gaps in health services by geographic region can assist to improve service availability. Alternate service delivery methods, such as telehealth, may assist to reduce the associated burden of travel for those in regional areas.


Spatial-temporal risk assessment of urbanization impacts on ecosystem services based on pressure-status - response framework.
Rapid urbanization is a global phenomenon that has altered many ecosystems, generating ecological risks such as causing a decline in many ecosystem services. In this study, ecosystem service oriented risk assessment combined with PSR were quantifying how urbanization influences the ecosystem services about Beijing-Tianjin-Hebei urban agglomeration of China between 2000 year and 2010 year. The mean value of ecosystem services in three gradient (rural areas, suburban, and urban area) declined from 4.12 Yuan/m2 to 1.75 Yuan/m2 in 2000 year, while the mean value in 2010 year showed significant decrease and also represented urban-rural gradient. The average of pressure in PSR framework increased from 0.145 to 0.162 between two periods, while the average of status decrease from 0.378 to 0.311, and the status value decrease from 0.096 to 0.087. The higher risk degree V increased 6.95% between two periods, while the lower risk degree I decrease 6.89%. Two main types including high value gathering field and low value gathering field existed between two periods, the higher gathering field owned the ratio of 9.85%, mainly distributed around the urban area of Beijing and Tianjin, while the lower gathering field possess the ratio of 10.69%, mainly distributed in the northern and western in region. Overall, the analytical framework proposed in this study can provide comprehensive information to evaluate the impacts of complex practice in land-use planning and region ecosystem management.


Tetraspanins: Spanning from solid tumors to hematologic malignancies.
Tetraspanins (tetraspans or TM4SF) are a family of integral membrane proteins with four transmembrane helices, a small extracellular loop, and a large extracellular loop. Although tetraspanins are expressed in many types of cells, including immune cells, their biological roles are not fully defined. Nonetheless, recent studies have revealed the important roles of tetraspanins in solid tumors and hematologic malignancies, and expression of tetraspanins is associated with the malignancy of human tumors. Furthermore, genetic mouse models of tetraspanins highlight their contribution to tumorigenesis. In this review, we summarize the implication of tetraspanins in cancer with a special focus on tetraspanin 3 in myeloid leukemia. Our increasing knowledge of tetraspanins and the pathologies that alter their function will undoubtedly inform the rational design of novel cancer therapies.


Bias in Surgical Residency Evaluations: A Scoping Review.
Given widespread disparities in the surgical workforce and the advent of competency-based training models that rely on objective evaluations of resident performance, this review aims to describe the landscape of bias in the evaluation methods of residents in surgical training programs in the United States. A scoping review was conducted within PubMed, Embase, Web of Science, and ERIC in May 2022, without a date restriction. Studies were screened and reviewed in duplicate by 3 reviewers. Data were described descriptively. English-language studies conducted in the United States that assessed bias in the evaluation of surgical residents were included. The search yielded 1641 studies, of which 53 met inclusion criteria. Of the included studies, 26 (49.1%) were retrospective cohort studies, 25 (47.2%) were cross-sectional studies, and 2 (3.8%) were prospective cohort studies. The majority included general surgery residents (n = 30, 56.6%) and nonstandardized examination modalities (n = 38, 71.7%), such as video-based skills evaluations (n = 5, 13.2%). The most common performance metric evaluated was operative skill (n = 22, 41.5%). Overall, the majority of studies demonstrated bias (n = 38, 73.6%) and most investigated gender bias (n = 46, 86.8%). Most studies reported disadvantages for female trainees regarding standardized examinations (80.0%), self-evaluations (73.7%), and program-level evaluations (71.4%). Four studies (7.6%) assessed racial bias, of which all reported disadvantages for trainees underrepresented in surgery. Evaluation methods for surgery residents may be prone to bias, particularly with regard to female trainees. Research is warranted regarding other implicit and explicit biases, such as racial bias, as well as for nongeneral surgery subspecialties.


Synthesis of 2-substituted 9-oxa-guanines {5-aminooxazolo[5,4-d]pyrimidin-7(6H)-ones} and 9-oxa-2-thio-xanthines {5-mercaptooxazolo[5,4-d]pyrimidin-7(6H)-ones}.
Oxazolo[5,4-d]pyrimidines can be considered as 9-oxa-purine analogs of naturally occurring nucleic acid bases. Interest in this ring system has increased due to recent reports of biologically active derivatives. In particular, 5-aminooxazolo[5,4-d]pyrimidine-7(6H)-ones (9-oxa-guanines) have been shown to inhibit ricin. The preparation of a series of 2-substituted 5-aminooxazolo[5,4-d]pyrimidin-7(6H)-ones and related 5-thio-oxazolo[5,4-d]pyrimidines is described, including analogs suitable for further elaboration employing "click" chemistry utilizing copper-catalyzed Huisgen 1,3-dipolar cycloadditions. Two of the compounds prepared were found to inhibit ricin with IC(50)ca. 1-3 mM.


Level of endothelial cell apoptosis required for a significant decrease in microvessel density.
Endothelial cell apoptosis plays a critical role in the disruption of blood vessels mediated by natural inhibitors of angiogenesis and by anti-vascular drugs. However, the proportion of endothelial cells required to mediate a significant decrease in microvessel density is unknown. A system based on an inducible caspase (iCaspase-9) offers a unique opportunity to address this question. The dimerizer drug AP20187 induces apoptosis of human dermal microvascular endothelial cells stably transduced with iCaspase-9 (HDMEC-iCaspase-9), but not control cells (HDMEC-LXSN). Here, we generated blood vessels containing several HDMEC-iCaspase-9:HDMEC-LXSN ratios, and developed a mathematical modeling involving a system of differential equations to evaluate experimentally inaccessible ratios. A significant decrease in capillary sprouts was observed when at least 17% of the endothelial cells underwent apoptosis in vitro. Exposure to vascular endothelial growth factor (VEGF(165)) did not prevent apoptosis of HDMEC-iCaspase-9, but increased the apoptotic requirement for sprout disruption. In vivo experiments showed the requirement of at least 22% apoptotic endothelial cells for a significant decrease in microvascular density. The combined use of biological experimentation with mathematical modeling allowed us to conclude that apoptosis of a relatively small proportion of endothelial cells is sufficient to mediate a significant decrease in microvessel density.


Rostral brainstem contributes to medullary inhibition of muscle tone.
It has long been known that stimulation of the medial medulla in the decerebrate animal produces bilateral inhibition of muscle tone. In the present study we have found that transection of the brainstem at the ponto-medullary junction attenuates this inhibition. An interaction between medullary and rostal brainstem systems is responsible for the medullary inhibition phenomenon. A similar interaction may produce the inhibition of muscle tone seen in REM sleep.


Successful treatment of severe recalcitrant vernal keratoconjunctivitis and atopic dermatitis associated with elevated IgE levels with omalizumab.
We report the clinical case of an atopic patient with important manifestations impacting the quality of life at the cutaneous and ocular site. The condition resisted conventional treatments, and omalizumab had to be used to treat the disease successfully.


[Incidence of insertion difficulty using Proseal LMA and the efficacy of recommended insertion maneuvers].
According to the instruction manual, the sniffing position (SP) and the slight lateral approach (SLA) are the recommended insertion methods using Proseal laryngeal mask airway (PLMA). However, the efficacy of these methods has not been assessed. The incidence and the reason of the insertion with difficulty were assessed in 50 adult patients. And then, the efficacy of these methods in the patient with insertion difficulty was studied. Establishment of the airway was unsuccessful in 10 patients at first attempt. The commonest reason of unsuccessful attempt was failure to slide PLMA into the pharynx. The insertion was successful and patent airway was obtained using Full-SP and SLA in 8 of the 10 patients. It was suggested that Full-SP and SLA were useful to place PLMA in patients with insertion difficulty.


Renal cysts: can percutaneous ethanol injections be considered an alternative to surgery?
To evaluate the efficacy of a new sclerotization technique with pure ethanol in the treatment of symptomatic renal cysts. Fourteen patients having renal cysts with a meant diameter of 10 (range 5-15) cm were treated. Our technique includes: ultrasound-guided percutaneous puncture with an 18-gauge needle, positioning of a 5-Fr catheter, complete cyst fluid aspiration, injection of pure alcohol equal to 15% of the initial cyst volume, and alcohol aspiration after 90 min. The procedure was repeated eight times within 5 days. The patients were followed up by ultrasound and/or CT scan for 1 year. All patients became symptom free. Follow-up showed a progressive reduction of the cyst diameter in all cases. Three cysts only (in 2 patients; cyst diameter <2 cm) persisted after 12 months. No significant complications were observed. In our experience, injections of pure ethanol in renal cysts, repeated after some days, were effective in eliminating recurrences and related symptoms. The procedure was not associated with significant complications. Our findings suggest that it be considered the first-choice procedure in the treatment of renal cysts, due to the good results and the low cost of ethanol.


Loss of ERdj5 exacerbates oxidative stress in mice with alcoholic liver disease via suppressing Nrf2.
Alcoholic liver disease is the major cause of chronic liver diseases. Excessive alcohol intake results in endoplasmic reticulum (ER) stress. ERdj5, a member of DNAJ family, is an ER-resident chaperone protein, whose role in alcoholic liver disease remains to be investigated. In this study, we aim to address the effect of ERdj5 on alcoholic liver disease and the underlying mechanism. Hepatic Dnajc10 (ERdj5) mRNA expression was elevated in both human and mouse alcoholic hepatitis. In mice subjected to chronic and binge ethanol feeding, ERdj5 levels were also markedly increased. Hepatic Dnajc10 correlated with Xbp1s mRNA. Tunicamycin, an ER stress inducer, increased ERdj5 levels. Dnajc10 knockout mice exhibited exacerbated alcohol-induced liver injury and hepatic steatosis. However, the macrophage numbers and chemokine levels were similar to those in wild-type mice. Depletion of Dnajc10 promoted oxidative stress. Ethanol feeding increased hepatic H2O2 levels, and these were further increased in Dnajc10 knockout mice. Additionally, Dnajc10-deficient hepatocytes produced large amounts of reactive oxygen species. Notably, Nrf2, a central regulator of oxidative stress, was decreased by depletion of Dnajc10 in the nuclear fraction of ethanol-treated mouse liver. Consistently, liver tissues from ethanol-fed Dnajc10 knockout mice had reduced expression of downstream antioxidant genes. Furthermore, hepatic glutathione content in the liver of knockout mice declined compared to wild-type mice. In conclusion, our results demonstrate that ethanol-induced ERdj5 may regulate the Nrf2 pathway and glutathione contents, and have protective effects on liver damage and alcohol-mediated oxidative stress in mice. These suggest that ERdj5 has the potential to protect against alcoholic liver disease.


Control of rural house infestation by Triatoma infestans in the Bolivian Chaco using a microencapsulated insecticide formulation.
Triatoma infestans, the main vector of Trypanosoma cruzi (causative agent of Chagas disease) has been successfully eliminated over much of its original geographic distribution over the southern cone countries of South America. However, populations of the species are still infesting houses of rural communities of the Gran Chaco region of Argentina and Bolivia. This study reports for the first time a large-scale effect of a vector control intervention using a microencapsulated formulation of organophosphates and insect growth regulator on house infestation by T. infestans, in the southwestern region of Santa Cruz de la Sierra Department, within the Bolivian chaco. The vector control intervention included the treatment and entomological evaluation of 1626 individually coded and georeferenced houses with the microencapsulated formulation. House infestation by T. infestans was evaluated by active searches with fixed capture effort carried out before and after two, 16 and 32 months of the treatment application. House infestation prevalence was 30.5% before the intervention, spatially aggregated in two clusters of 38 and 25 localities that showed 41% and 38% house infestation by T. infestans. Infestation prevalence was reduced to 2.4% two months after the intervention and remained very low (1.7%) until the end of the study after 32 months of the control intervention, without any other additional vector control intervention. The obtained results show an important long lasting effect on house protection against triatomine infestation in a region of known pyrethroid resistant populations of T. infestans, as the result of the slow release of the active ingredients, protected by the formulation microcapsule.


Importance of algae in the diet of the oligochaetes Lumbriculus variegatus (MÜller) and Rhyacodrilus sodalis (Eisen).
The importance of algae in the diet of the oligochaetes Lumbriculus variegatus and Rhyacodrilus sodalis was determined from cellections made in a eutrophic bay from April 1977 to April 1978. During the summer, algae represented 70-85% of the gut contents of both species. The most frequently ingested algae were Cymatopleura elliptica, Cymbella spp., Epithemia turgida, Pinnularia spp., and Synedra ulna. Almost all species were consumed in proportion to their abundance in the environment. However, Nostoc pruniforme and Nostoc verrucosum were not eaten due to size selection. The high level of algal consumption exhibited by the oligochaetes was primarily related to the large standing crop of algae on the sediments. During the winter, when algal densities were low in the environment, detritus and associated bacteria were the major food source.


Altered electrodermal responsivity associated with clinical pain.
We used certain physiologic maneuvers to perturb the autonomic nervous system (ANS) in an attempt to detect a link between the ANS and pain. In the unperturbed state, we found no difference in the electrodermal response among normal controls, preoperative patients (increased stress without pain) and postoperative patients (increased stress and pain). The electrodermal response elicited by autonomic maneuvers was significantly attenuated in postoperative patients but not in preoperative patients or in normal control subjects.


The ten year cycle of the willow grouse of Lower Kolyma.
The population of willow grouse (Lagopus lagopus) in the Lower Kolyma district of Yakutia, USSR, shows cycles of abundance with a period of about 10 years. Observations habe been made for 2-5 months each year since 1977. This paper attempts to explain why the period of population depression is so long (3-4 years) and why the peak population density is so high. In "normal" years birds occupied only the 3%-4% of the whole area that consisted of preferred biotope, while during the population peak the less preferred "placour tundra" was also occupied. The most important factor affecting population numbers was the proportion of non-breeding birds, which ranged from 62% in 1981 (population peak) to close to zero in 1979. The high proportion of non-breeding birds in 1980 and 1981 was preceded by deficient winter diets and poor spring nutrition. When the birds arrive at their breeding grounds they defend a territory, which enables them to compensate for winter weight loss and gain condition for breeding. There was a strong negative correlation between territory size and willow biomass density (an index of territory quality). In preferred biotopes birds used only about 8%-12% of resource annually, but the less preferred biotopes were used very intensively. Probably the periodical high peaks and long troughs in willow grouse numbers can be explained as follows. For 2 or 3 years birds can use vast areas with only a low density of suitable food to support reproduction. When these resources are exhausted they take a long time to recover. Meanwhile the grouse population is restricted to patches where with willows abundant, of varying quality, and only a few of them (less than 1% of the total area) may permanently support a high density of willow grouse.


Studies on the physiology of pollen and pollen tube growth. IV Eschscholtzia californica Cham.
Eschscholtzia californica stigmas with germinating pollen at different stages of development were the subject of histochemical studies which aimed the localization of several enzymes like phosphorylase, leucine amino peptidase, nonspecific esterase, cytochrome oxidase, aldolase, alpha-glycerophosphate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, monoamine oxidase, alpha-galactosidase, beta-glucosidase and beta-galactosidase. Pollen and pollen tubes were shown to contain starch, lipid, proteins and soluble sugars as the storage products. These storage products were utilized during germination and tube growth. The role of different enzymes in the process of germination and tube growth is discussed. From the distribution of oxidoreductases it is inferred that respiration plays an essential role in the tube growth. During pollen germination probably the reserve proteins were transported to pollen tube tip. The increase of activity of alpha-and beta-galactosidase in pollen tubes indicates on their involvement in carbohydrate metabolism. The role of alpha-galactosidase in the metabolism of galactolipids is also inferred. Similarly, the reaction catalysed by beta-glucosidase resulted in the production of aglycon and glucose; of these the former possibly act as a substrate of peroxidase. Some of the glycosidases diffused out of pollen wall on the stigma and participated in the release of free sugars of the female tissue.


Immunoglobulin concentrations in first-degree relatives of epileptic patients with drug-induced IgA deficiency.
Serum immunoglobulins A, G and M were studied in parents and siblings of 16 patients being treated for epilepsy. Five healthy families served as controls. Seven of the patients were low IgA-responders and the rest of the patients had shown normal IgA-levels during treatment. None of the parents and siblings studied showed a serum-IgA deficiency, with the exception of one mother who was being treated for rheumatoid arthritis with naproxen. Low serum concentrations of IgG and IgM were not found. A significantly increased IgM-level was found in first-degree relatives of the low IgA-responders, and the siblings of low 2gA-responders had significantly raised IgA in their sera.


Indian plate paleogeography, subduction and horizontal underthrusting below Tibet: paradoxes, controversies and opportunities.
The India-Asia collision zone is the archetype to calibrate geological responses to continent-continent collision, but hosts a paradox: there is no orogen-wide geological record of oceanic subduction after initial collision around 60-55 Ma, yet thousands of kilometers of post-collisional subduction occurred before the arrival of unsubductable continental lithosphere that currently horizontally underlies Tibet. Kinematically restoring incipient horizontal underthrusting accurately predicts geologically estimated diachronous slab break-off, unlocking the Miocene of Himalaya-Tibet as a natural laboratory for unsubductable lithosphere convergence. Additionally, three endmember paleogeographic scenarios exist with different predictions for the nature of post-collisional subducted lithosphere but each is defended and challenged based on similar data types. This paper attempts at breaking through this impasse by identifying how the three paleogeographic scenarios each challenge paradigms in geodynamics, orogenesis, magmatism or paleogeographic reconstruction and identify opportunities for methodological advances in paleomagnetism, sediment provenance analysis, and seismology to conclusively constrain Greater Indian paleogeography.


Early alterations in the morphology of cytomegalovirus-infected human fibroblasts.
Cytomegalovirus-infected human fibroblasts developed large numbers of fine microvilli within 90 min after addition of virus. The structure of these microvilli gradually changed as the infection proceeded, although the infected cells were easily detected by their large number of processes. These processes may be involved in the increased transport of ions and nutrients into the infected cell.


Who is unlikely to report adverse events after vaccinations to the Vaccine Adverse Event Reporting System (VAERS)?
Healthcare provider (HCP) reporting to the Vaccine Adverse Event Reporting System (VAERS) is important to assuring the safety of U.S. licensed vaccines. HCP awareness of and practices regarding reporting of adverse events following immunization (AEFI) is understudied. A large, nationally representative sample of U.S. office-based HCP across three occupational groups (physicians, mid-level providers [physician assistants, advanced practice nurses] and nurses) and three primary care practice areas (pediatrics, family medicine, internal medicine) were surveyed utilizing standardized methodology. We assessed HCP familiarity with VAERS, the situations under which they were likely to report an AEFI, and the methods they used and preferred for reporting. We used logistic regression to determine factors associated with HCP not reporting AEFI to VAERS. Our survey response rate was 54.9%. The percentage of HCP aware of VAERS (71%) varied by occupation and primary care practice area. About 37% of HCP had identified at least one AEFI with only 17% of these indicating that they had ever reported to VAERS. More serious events were more likely to be reported. Factors associated with HCP not reporting AEFI included: HCP not familiar versus very familiar with filing a paper VAERS report (OR=12.84; p<0.0001), primary care practice area of internal medicine versus pediatrics (OR=4.22; p=0.0005), and HCP not familiar versus very familiar with when it was required to file a VAERS report (OR=5.52; p=0.0013). Specific educational interventions targeted to HCP likely to see AEFI but not currently reporting may improve vaccine safety reporting practices.


Undifferentiated altered mental status: a late presentation of toxic acetaminophen ingestion.
Altered mental status is a common undifferentiated presentation in the emergency department. We describe a case of acetaminophen-induced acute liver failure that was diagnosed and treated prior to obtaining definitive historical or laboratory information about the etiology. The physical exam finding of scleral icterus in this case was a key element to rapid identification and treatment of this life-threatening condition. A discussion of appropriate N-acetylcysteine treatment for acute liver failure and acetaminophen intoxication is included.


Survey on the PABC recognition motif PAM2.
The PABP-interacting motif PAM2 has been identified in various eukaryotic proteins as an important binding site for the PABC domain. This domain is contained in homologs of the poly(A)-binding protein PABP and the ubiquitin-protein ligase HYD. Despite the importance of the PAM2 motif, a comprehensive analysis of its occurrence in different proteins has been missing. Using iterated sequence profile searches, we obtained an extensive list of proteins carrying the PAM2 motif. We discuss their functional context and domain architecture, which often consists of RNA-binding domains. Our list of PAM2 motif proteins includes eukaryotic homologs of eRF3/GSPT1/2, PAIP1/2, Tob1/2, Ataxin-2, RBP37, RBP1, Blackjack, HELZ, TPRD, USP10, ERD15, C1D4.14, and the viral protease P29. The identification of the PAM2 motif in as yet uncharacterized proteins can give valuable hints with respect to their cellular function and potential interaction partners and suggests further experimentation. It is also striking that the PAM2 motif appears to occur solely outside globular protein domains.


The diel pattern in harbour porpoise clicking behaviour is not a response to prey activity.
Wild harbour porpoises (Phocoena phocoena) mainly forage during the night and, because they rely on echolocation to detect their prey, this is also when they are most acoustically active. It has been hypothesised that this activity pattern is a response to the diel behaviour of their major prey species. To test this hypothesis, we monitored the acoustic activity of two captive harbour porpoises held in a net pen continuously during a full year and fed by their human keepers during daylight hours, thus removing the influence of prey activity. The porpoises were exposed to similar temperature and ambient light conditions as free-ranging animals living in the same region. Throughout the year, there was a pronounced diel pattern in acoustic activity of the porpoises, with significantly greater activity at night, and a clear peak around sunrise and sunset throughout the year. Clicking activity was not dependent on lunar illumination or water level. Because the porpoises in the pen are fed and trained during daylight hours, the results indicate that factors other than fish behaviour are strongly influencing the diel clicking behaviour pattern of the species.


Use of anti-diabetic drugs and glycaemic control in type 2 diabetes-tThe Hong Kong Diabetes Registry.
In this report, we examined the usage of anti-diabetic treatments including oral anti-diabetic drug (OAD) and/or insulin and their combination from baseline data of a consecutive cohort of 7549 Chinese type 2 diabetic subjects in the Hong Kong Diabetes Registry. Pattern of usage of anti-diabetic treatment and corresponding glycemic control was analyzed. OAD failure was defined as the need to add insulin to maintain glycemic target (glycated hemoglobin, HbA(1c) level<7%) with or without continuation of OAD. There were 4109 [54.4%] women and 3440 [45.6%] men (age: median 57.0 years; range 13-92 years). The mean HbA(1c) level was 7.7+/-1.8% with 39.7% attaining glycemic target. Long disease duration was associated with more complex regimens and the respective rates of OAD failure requiring insulin use were 23.7%, 39.3%, 57.1% and 75.9% in those with disease duration <5 years, 5-9.9 years, 10-19.9 years and > or =20 years (p<0.001). In conclusion, in a clinic-based type 2 diabetic population, 39.7% attained glycemic target with HbA(1c)<7%. Long disease duration and complexity of treatment regimens were associated with suboptimal glycemic control. Early intensification of therapy and system improvement are needed to enhance the effectiveness of these drugs in clinical practice.


Starchy biomass-powered enzymatic biofuel cell based on amylases and glucose oxidase multi-immobilized bioanode.
The present study reports the design of a novel bioanode to directly utilize starch as a fuel in an enzymatic biofuel cell. The enzymatic fuel cell is based on three enzymes (alpha-amylase, glucoamylase and glucose oxidase). The carbon paste electrode containing these three enzymes and tetrathiafulvalene can both saccharize and oxidize starchy biomass. In cyclic voltammetry, catalytic currents were successfully observed with both glucose and starchy white rice used as a substrate. Finally, a membrane-less white rice/O2 biofuel cell was assembled and the electrochemical performance was evaluated. The three enzyme based electrode was used as a bioanode and an immobilized bilirubin oxidase (derived from Myrothecium verrucaria) electrode was used as a biocathode. The biofuel cell delivered an open circuit voltage of 0.522V and power density of up to 99.0 μWcm(-2). Our results show that a readily available fuel can be used for enzymatic fuel cells, and will lead to new designs.


Recombinant adenovirus type 5 vectors that target DC-SIGN, ChemR23 and alpha(v)beta3 integrin efficiently transduce human dendritic cells and enhance presentation of vectored antigens.
Recombinant adenoviruses (rAds) represent a promising system for vaccine delivery but transduce dendritic cells (DC) relatively poorly. To address this concern, we used a biotin-avidin linkage to conjugate rAd vectors to ligands which bind with high affinity to selected receptors on DC (ChemR23, alpha(v)beta3 integrin, and DC-SIGN). The targeted vectors had an enhanced ability to transduce human monocyte-derived DC compared to untargeted virus. In addition, DC transduced with targeted rAd vectors were more efficient at stimulating cytokine production by autologous memory CD8+ T cells, against a vector-encoded antigen. These results expand the range of cell surface receptors that can be used to target rAd5 vectors to DC, and may facilitate future development of rAd-based vaccines.


Modulation of pulmonary inflammatory responses and antimicrobial defenses in mice exposed to diesel exhaust.
Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and antimicrobial defenses in an exposure model that had previously been shown to increase susceptibility to influenza. BALB/c mice were exposed to filtered air, or to DE diluted to yield 0.5 or 2 mg/m(3) of diesel exhaust particles (DEP) for 4 h per day for 1 or 5 days. Immediately and 18 h after one or five diesel exposures mice were euthanized to assess both immediate and delayed effects. DE exposure for 5 days at either concentration caused higher neutrophil numbers and lesion scoring compared to air controls. Intracellular adhesion molecule-1 (ICAM-1), which recruits inflammatory cells and is an entry site for rhinoviruses was increased immediately after 1 or 5 days of DE exposure. Several inflammatory and immune cytokines (TNF-alpha, MIP-2, IL-6, IFN-gamma, and IL-13) were also upregulated at various time points and concentrations. In contrast, clara cell secretory protein (CCSP), surfactant protein A (SP-A), and surfactant protein D (SP-D) which are important host defense molecules, were significantly decreased at both the message and protein level with DE exposure. We conclude that exposure to moderate and high occupational levels of DE caused an increase in lung injury and inflammation, and a decrease in host defense molecules, which could result in increased susceptibility to respiratory pathogens.


[High signal intensity of flowing blood in MR tomograms as an indication of changed flow characteristics].
A case report points to a venous obstruction expressed by high signal intensities in the MR tomogram that had not been noted so far when using this method.