Colloidal Capsules Assembled from Gold Nanoparticles using Small Molecule Hydrophobic Crosslinkers.
Colloidal capsules (or colloidosomes) have been studied for various applications such as therapeutic agent encapsulation, photothermal therapy, imaging, and energy storage. Emulsion-based synthesis is the most common approach to preparing colloidal capsules as it is relatively straightforward and scalable. However, while the initial formation requires only introducing the colloidal subunits into an emulsion and letting them assemble at the interface, a second step is required in order to prepare stable, covalently linked colloidal capsules and preparing sub-micron colloidal capsules is quite challenging. Here we describe a simple and quick one-step method to synthesize covalently linked, stable nanoscale colloidal capsules consisting of gold nanoparticles (AuNP) and thiol-containing crosslinkers. Gold nanoparticle capsules (AuNCs) were formed by coating microemulsion droplets containing thiol-containing crosslinkers with citrate-stabilized AuNPs. The physicochemical properties of the colloidal capsules can be tailored by changing the building blocks. In order to demonstrate this, colloidal capsules were assembled from AuNPs ranging from 5 nm to 20 nm in size. The use of the larger 20 nm starting particles resulted in AuNCs with a sufficiently pronounced red shift for λmax to be suitable for biological photothermal applications, where use of a NIR laser is strongly preferred. The AuNCs were found to be biocompatible and stable in cell culture condition and to provide moderate heating. This demonstrates the modularity of the synthesis and the potential advantages of a one-step synthesis to prepare nanoscale gold colloidal capsules.


Synaptology of cultured olfactory bulb cells.
Cultured embryonic mouse olfactory bulb cells formed asymmetric, symmetric, axodendritic, and dendrodendritic synapses. These neurons contained electron lucent, dense core, and coated vesicles. Dense core and coated vesicles had an average diameter of 71 and 80 nm, respectively. Two statistically different populations of electron lucent vesicles were found, based on synaptic symmetry: electron lucent vesicles from asymmetric synapses had an average diameter of 46 nm with an estimated volume of 49,000 nm3, whereas those from symmetric synapses had an average diameter of 44 nm and an estimated volume of 42,000 nm3. Because these values are similar to those found for intact olfactory bulb, the synapses of these cultured cells have some of the same morphological characteristics as those in the intact olfactory bulb.


Questioning validity in the area of ergonomics/human factors.
This paper focuses on the analysis of deviation in findings within ergonomics/human factors (E/HF) research. The current terms used to address the analysis of deviation in empirical research revolve around the notion of validity. In E/HF research papers, 'validity' is widely interpreted and includes its common parlance usage. More importantly, analysis frequently limits 'validation' to the equivalent of 'verification', eventually resulting in 'validity' as a label of little significance. To clarify the analysis of deviation, 'investigative syntaxes' are introduced to show what exactly should or can be questioned when deviation is observed, i.e. either empirical findings or propositions, and how this questioning can be structured. The possibility is discussed that, with or without the help of these syntaxes, validation may become a method of inquiry; a productive means of generating significant theoretical questions which bear directly on empirical work.


Expression of pro-apoptotic (p53, p21, bax, bak and fas) and anti-apoptotic (bcl-2 and bcl-x) proteins in serous versus mucinous borderline ovarian tumours.
We examined the expression of apoptosis-related proteins in serous versus mucinous borderline ovarian tumours, in comparison with benign and malignant ovarian tumours. Immunohistochemical expression of pro-apoptotic (p53, p21, bax, bak, fas) and anti-apoptotic proteins (bcl-2, bcl-x) was determined in 34 borderline (19 mucinous, 15 serous), 20 benign (10 mucinous, 10 serous) and 28 malignant ovarian tumours (9 mucinous, 19 serous). A difference in semi-quantitative p53 expression was found between benign and borderline tumours (P = 0.01), but not between borderline and malignant tumours. Increased p21 expression was found in borderline versus benign tumours (P = 0.004). Bcl-2 expression was lower in borderline than in benign (P = 0.01) and malignant tumours (P = 0.02). No difference in bax, bak, fas or bcl-x expression was observed among the three tumour types. Higher percentage of p21 positive cells was found in serous than in mucinous borderline tumours (P < 0.001). Bcl-2 expression was higher in serous than in mucinous forms of benign (P < 0.001), borderline (P < 0.001), and malignant tumours (P < 0.003). No difference in p53, bax, bak, fas or bcl-x expression was observed between serous and mucinous borderline ovarian tumours. Although p53 overexpression was a common feature of both mucinous and serous borderline tumours, p21 and bcl-2 overexpression appeared specific to serous tumours.


Multiple inflammatory markers in patients with significant coronary artery disease.
Several inflammatory biomarkers are linked to cardiovascular risk. In order to investigate their coexistence and relative responses, several established and two novel markers (lactoferrin and the terminal complement complex), representing infection and central components of inflammation, were measured simultaneously in patients undergoing first-time coronary angiography. Blood samples from patients with (n=131) or without (n=103) significant coronary artery stenosis were analyzed for plasma markers representing endothelium, platelets, neutrophils, monocytes, and complement, C-reactive protein, and antibodies against the infectious agents Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus. In multivariate logistic regression analysis, hypercholesterolemia (p<0.001), increased concentrations of the neutrophil activation marker lactoferrin (p<0.001) and the monocyte activation marker neopterin (p=0.012), lower concentrations of the terminal complement complex (p<0.001), and antibodies against C. pneumoniae (p=0.023) were variables linked to coronary artery stenosis. In univariate analysis additional relationships were found to current smoking (p<0.001), increased plasma concentrations of vascular cell adhesion molecule-1 (p=0.015), E-selectin (p<0.01), myeloperoxidase (p=0.051) and endothelin-1 (p=0.053), as well as diabetes (p=0.039). Activation of multiple inflammatory pathways and C. pneumoniae infection may influence the inflammatory response in atherosclerosis. These pilot data provide an indication of the relative usefulness of various inflammatory biomarkers, indicating that the novel markers lactoferrin and the terminal complement complex warrant further investigation.


Psychological processes and histories associated with nonepileptic versus epileptic seizure presentations.
Nonepileptic seizures (NES) provide a clinical challenge as the mechanisms involved remain uncertain. The present study compares 27 participants with confirmed NES presentations with 39 individuals with epileptic seizure (ES) presentations only, on indices of psychopathology, trauma history, dissociative propensity, and attachment style. Psychopathology and dissociation were found to be significantly elevated in the NES group compared with the ES group. No differences were found between groups in terms of trauma history and attachment style. However, trauma history did correlate significantly with psychopathology in the NES group but not in the ES group. Finally, whereas the relationship between psychological variables and seizure frequency was weak within the ES group, trauma history, a fearful attachment dimension, psychopathology, and dissociation predicted seizure frequency in the NES group. Implications for understanding and interventions with NES presentations are discussed.


Rationale and design for the Vaginal Erbium Laser Academy Study (VELAS): an international multicenter observational study on genitourinary syndrome of menopause and stress urinary incontinence.
The genitourinary syndrome of menopause (GSM) and stress urinary incontinence (SUI) are common clinical challenges for women's health and quality of life. The laser treatment and particularly the vaginal erbium laser (VEL) may provide a new non-invasive treatment for both GSM and SUI. However, the estimation of the ultimate results of different laser treatments may be altered by different issues, such as patient selection, concomitant treatments, and long-term effect of vaginal laser thermotherapy. In the present paper, we present the protocol for a large multicenter study on the evaluation of the efficacy and safety of VEL for the treatment of GSM and SUI, the Vaginal Erbium Laser Academy Study (VELAS). This study will evaluate the effects of three laser applications in 1500 postmenopausal women. Subjective and objective symptoms will be evaluated prior to the first laser treatment with follow-up visits after 4 weeks from the last laser application, and subsequently after every 3 months for 1 year. Findings from the VELAS have the potential to affect clinical care practice and health decisions for millions of women world-wide for a non-hormonal treatment for GSM and a non-invasive treatment of SUI.


Simplified progressive approach for the ablation of scar related atrial macroreentrant tachycardias.
Radiofrequency ablation of scar related right atrial flutter is challenging. Long procedures, prolonged fluoroscopic times and high percentages of recurrences are of concern. We present a simple and progressive approach based on a single electroanatomic map of the right atrium. Twenty-two consecutive patients with atrial flutter and history of cardiac surgery were included. An electrophysiologic study was performed to define localization (left or right) and cavo-tricuspid isthmus participation using entrainment mapping. After a critical isthmus was localized, ablation was performed with an external irrigated tip catheter with a power limit of 30 W. Potential ablation sites were confirmed by entrainment. The predominant cardiopathy was atrial septal defect. All arrhythmias were localized in the right atrium; mean cycle length of the clinical flutter was 274 ± 31 ms. Only 40% had cavo-tricuspid isthmus participation. None of the patients with successful ablation had recurrences after 13 ± 9.4 months of follow-up. A progressive approach with only one activation/voltage CARTO(®) map of the atrium and ablation of all potential circuits is a highly effective method for ablating scar related macroreentrant atrial arrhythmias.


Oral acyclovir in herpetic keratitis.
A double blind comparative study of oral acyclovir and acyclovir ophthalmic ointment was carried out on 29 patients with simple herpetic dendritic corneal ulceration. Patients were randomly allocated to the study. Healing was achieved in all fourteen patients treated with acyclovir ointment, and in fourteen out of fifteen patients treated with oral acyclovir. The mean healing time of 5.6 days was identical for both patient groups. There was no significant systemic or local side effects recorded in either group. The level of acyclovir in tear fluid was measured, and in patients receiving oral acyclovir the level was in excess of the ED50 of herpes simplex virus type 1.


Differential effects of intravenous anesthetics on PDGF-BB-induced vascular smooth muscle cell migration.
Intravenous anesthetics are used during the perioperative and/or postoperative period in critically ill patients. Vascular smooth muscle cells (VSMCs) play important roles in vascular injury repair or restenosis after intervention. We previously reported that platelet-derived growth factor (PDGF)-BB induces VSMC migration via extracellular signal-regulated kinase (ERK) and Akt in a VSMC line, A10 cells. In the present study, we investigated the effects of intravenous anesthetics on PDGF-BB-induced VSMC migration and the mechanism. VSMCs migration was assessed using Boyden chamber, and phosphorylation of each protein kinase was analyzed by Western blotting. Propofol or midazolam but not ketamine or dexmedetomidine suppressed PDGF-BB-induced A10 cells migration in a concentration-dependent manner. The suppressive effects on migration were observed also in human aortic smooth muscle cells. Propofol or midazolam did not affect phosphorylation of PDGF receptor β in A10 cells. Propofol or midazolam failed to affect PDGF-BB-induced phosphorylation of ERK or Akt. On the other hand, propofol or midazolam attenuated PDGF-BB-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), but did not affect phosphorylation of stress-activated protein kinase/c-Jun N-terminal kinase. Both ketamine and dexmedetomidine had no effect on the phosphorylation of p38 MAPK induced by PDGF-BB. These results strongly suggest that propofol or midazolam inhibits VSMC migration by PDGF-BB via suppression of p38 MAPK activation. Propofol or midazolam may affect VSMC function in critically ill patients.


Creating objective and measurable postgraduate year 1 residency graduation requirements.
The process of developing objective and measurable postgraduate year 1 (PGY1) residency graduation requirements and a progress tracking system is described. The PGY1 residency accreditation standard requires that programs establish criteria that must be met by residents for successful completion of the program (i.e., graduation requirements), which should presumably be aligned with helping residents to achieve the purpose of residency training. In addition, programs must track a resident's progress toward fulfillment of residency goals and objectives. Defining graduation requirements and establishing the process for tracking residents' progress are left up to the discretion of the residency program. To help standardize resident performance assessments, leaders of an academic medical center-based PGY1 residency program developed graduation requirement criteria that are objective, measurable, and linked back to residency goals and objectives. A system for tracking resident progress relative to quarterly progress targets was instituted. Leaders also developed a focused, on-the-spot skills assessment termed "the Thunderdome," which was designed for objective evaluation of direct patient care skills. Quarterly data on residents' progress are used to update and customize each resident's training plan. Implementation of this system allowed seamless linkage of the training plan, the progress tracking system, and the specified graduation requirement criteria. PGY1 residency requirements that are objective, that are measurable, and that attempt to identify what skills the resident must demonstrate in order to graduate from the program were developed for use in our residency program. A system for tracking the residents' progress by comparing residents' performance to predetermined quarterly benchmarks was developed.


Arsenicibacter rosenii gen. nov., sp. nov., an efficient arsenic methylating and volatilizing bacterium isolated from an arsenic-contaminated paddy soil.
A novel bacterium with strong arsenic (As) methylation and volatilization abilities, designated strain SM-1T, was isolated from an As-contaminated paddy soil. SM-1T is strictly aerobic, rod-shaped, non-motile, Gram-negative and orange-coloured. Phylogenetic analysis revealed that strain SM-1T showed low 16S rRNA gene sequence similarities (≤88 %) to members of established genera in the family Cytophagaceae. Growth of this strain was observed at 15-45 °C (optimum, 37 °C), pH 6.0-8.0 (optimum, 7.0) and 0-0.5 % (w/v) NaCl. The major cellular fatty acids were C16 : 1ω5c and iso-C15 : 0. The respiratory quinone was MK-7, and the predominant polar lipids were phosphatidylethanolamine, an unidentified lipid (L), and an unidentified aminolipid (AL2). The DNA G+C content was 51.5 mol%. On the basis of phenotypic, phylogenetic and chemotaxonomic properties, strain SM-1T represents a novel species in a new genus within the family Cytophagaceae, for which the name Arsenicibacter rosenii gen. nov., sp. nov. is proposed. The type strain of Arsenicibacter rosenii is SM-1T (=CCTCC AB 2017086T=KCTC 52624T).


Profiling DNA methylation by bisulfite genomic sequencing: problems and solutions.
The surge of interest in DNA methylation during the last two decades has triggered an urgent need for an effective method to detect the methylation status of the cytosines in the genome. Bisulfite genomic sequencing is the most attractive choice so far for many laboratories. Various protocols have been established, but difficulties are often encountered, particularly by individuals who have limited experience in this field. This analysis presents a simple protocol that has consistently worked well in our laboratory. Discussions of potential technical problems and corresponding solutions are also included to facilitate the reproducibility of this protocol.


MicroRNA-298 Exacerbates Myocardial Ischemic Injury via Targeting Cyclin D1.
The aim of this study was to explore the role and regulatory mechanism of microRNA-298 (miR-298) in myocardial ischemic injury. H9c2 cardiomyocytes were cultured under hypoxia (3 % O₂) conditions to induce myocardial ischemic injury. Subsequently, the effects of miR-298 overexpression and suppression on hypoxia-induced myocardial damage in H9c2 cells were investigated. Moreover, the target of miR-298 was identified in H9c2 cells and the relationship between miR-298 and the activation of PTEN/PI3K/AKT signaling pathway was explored. miR-298 was upregulated in hypoxia-stimulated H9c2 cells. Overexpression of miR-298 distinctly aggravated hypoxia-induced myocardial damage in hypoxia-treated H9c2 cells, whereas inhibition of miR-298 alleviated hypoxia-induced injury. Moreover, miR-298 negatively regulated the expression of cyclin D1, and cyclin D1 was a target of miR-298 in H9c2 cells. Suppression of cyclin D1 significantly reversed the effects of suppression of miR-298 on hypoxia-induced myocardial damage. Lastly, inhibition of miR-298 activated the PTEN/PI3K/AKT signaling pathway, and this effect could be reversed after suppression of cyclin D1. Our results reveal that miR-298 may exacerbate myocardial ischemic injury by targeting cyclin D1 and regulating the activation of PTEN/PI3K/AKT signaling pathway. miR-298 may serve as a promising targets for reducing myocardial ischemic injury.


Effect of K, MG aspartate on some biological parameters of aging rats.
The effect of K and Mg salts of aspartic acid (Cardilan) on the serum concentration of selected proteins and phagocytic activity in aging male Wistar rats was investigated. Cardilan was administered in tap water for 7 days a month for 3 months before the last observed interval (12, 18 and 24 month). In a part of animals, the aging process was accelerated by sublethally gamma-irradiation. The administration of Cardilan slowed down the changes in the concentration of prealbumin, albumin, haptoglobin, haemopexin, C3 complement in non-irradiated rats (DC). This effect was extended to the changes in transferrin level in irradiated rats (IDC). The phagocytic activity in both DC, IDC rats was lower compared with controls drinking water (DW, IDW), but not significantly. The effect of Cardilan administration appears to be the greatest in 24-month-old rats, when the treated animals survived better by 25% in IDC group and by 26% better in DC rats, compared with those of the same age controls. Potassium and magnesium salts of aspartates are suitable compounds for life prolongation in the experimental conditions.


Holistic Considerations in Optimizing a Sterile Product Package to Ensure Container Closure Integrity.
A new major chapter dealing with container closure integrity was released by the United States Pharmacopeial Convention. Chapter <1207> provides a significant amount of education and guidance concerning test methodologies to prove that a system is integral and safe for use. The test method used is only one of the major considerations in approaching the challenge of proving an integral system. This paper takes a holistic review of all the major considerations needed in qualifying a new vial system for container closure integrity. There is substantial interplay among many aspects in the process of sealing a vial. This review helps to define major risks that need to be considered and mitigated and reinforces the need to understand the maximum allowable leakage limit that is acceptable for a specific drug application. A typical risk-based approach considers materials, test methods, process, people, environment, and equipment. Each of these aspects is considered in some detail along with a recommended process flow for building a best practice, science-based approach. This approach will inform decision making for evaluating the correct combination of components and assuring they are assembled and tested in an appropriate manner. This work, once completed, can be the basis for a vial system platform or specific drug application qualification.LAY ABSTRACT: Container closure integrity is a fundamental requirement of every sterile drug package. With recent upgrading of compendia standards and guidance around this issue, there is an opportunity to better define a best practice approach to a complicated subject. It is important to recognize that there is substantial interplay among the components of the system, the process of assembly, and the test methods that are used. This paper takes a holistic approach to discussing these issues and identifying the risks that must be considered in assuring an integral container over the shelf life of a drug product.


Time-related changes in intramuscular lipids of French dry-cured ham.
The aim of this study was to investigate the changes in intramuscular lipids during the processing of French dry-cured hams. In the fresh biceps femoris muscle, the lipid content was on average, 105 mg/g DM with a large individual variation. Glycerides accounted for about 75% of total lipids. During processing for 273 days, phospholipid content decreased markedly whereas free fatty acid content rose from 1·9 mg/g DM to 9·4 mg/g DM. Little change affected the fatty acid composition of both glycerides and phospholipids during processing. After a decrease in the proportion of polyunsaturated fatty acids during the first 2 months, free fatty acid composition remained stable. The results suggest that lipid alteration during dry-curing of hams is due to lipolysis and that lipid oxidation is limited.


Distribution of the native strain in human alpha 1-antitrypsin and its association with protease inhibitor function.
Serine protease inhibitors (serpins) are metastable in their native state. This strain, which is released upon binding to target proteases, is essential for the inhibitory activity of serpins. To understand the structural basis of the native strain, we previously characterized stabilizing mutations of alpha(1)-antitrypsin, a prototypical inhibitory serpin, in regions such as the hydrophobic core. The present study evaluates the effects of single point mutations throughout the molecule on stability and protease inhibitory activity. We identified stabilizing mutations in most secondary structures, suggesting that the native strain is distributed throughout the molecule. Examination of the substitution patterns and the structures of the mutation sites revealed surface hydrophobic pockets as a component of the native strain in alpha(1)-antitrypsin, in addition to the previously identified unusual interactions such as side chain overpacking and cavities. Interestingly, many of the stabilizing substitutions did not affect the inhibitory activity significantly. Those that affected the activity were confined in the regions that are mobilized during the complex formation with a target enzyme. The results of our study should be useful for designing proteins with strain and for regulating the stability and functions of serpins.


Development of an ultrasensitive immunoassay using affinity maturated antibodies for the measurement of rodent insulin.
The measurement of plasma insulin is important for clinical diagnosis of diabetes and for preclinical research of metabolic diseases, especially in rodent models used in drug discovery research for type 2 diabetes. Fasting immunoreactive insulin (F-IRI) concentrations are used to calculate the homeostasis model assessment ratio (HOMA-R), an index of insulin sensitivity. However, even the most sensitive commercially available enzyme-linked immunosorbent assay (ELISA) kits cannot measure the very low F-IRI concentrations in normal rats and mice. Therefore, we sought to develop a new rodent insulin ELISA with greater sensitivity for low F-IRI concentrations. Despite repeated efforts, high-affinity antibodies could not be generated by immunizing mice with mouse insulin (self-antigen). Therefore, we generated two weak monoclonal antibodies (13G4 and 26B2) that were affinity maturated and used to develop a highly sensitive ELISA. The measurement range of the sandwich ELISA with the affinity maturated antibodies (13G4m1 and 26B2m1) was 1.5 to 30,000 pg/ml, and its detection limit was at least 10 times lower than those of commercially available kits. In conclusion, we describe the development of a new ultrasensitive ELISA suitable for measuring very low plasma insulin concentrations in rodents. This ELISA might be very useful in drug discovery research in diabetes.


Biodegradation of carbofuran in soils within Nzoia River Basin, Kenya.
Carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) has been used within the Nzoia River Basin (NRB), especially in Bunyala Rice Irrigation Schemes, in Kenya for the control of pests. In this study, the capacity of native bacteria to degrade carbofuran in soils from NRB was investigated. A gram positive, rod-shaped bacteria capable of degrading carbofuran was isolated through liquid cultures with carbofuran as the only carbon and nitrogen source. The isolate degraded 98% of 100-μg mL(-1) carbofuran within 10 days with the formation of carbofuran phenol as the only detectable metabolite. The degradation of carbofuran was followed by measuring its residues in liquid cultures using high performance liquid chromatography (HPLC). Physical and morphological characteristics as well as molecular characterization confirmed the bacterial isolate to be a member of Bacillus species. The results indicate that this strain of Bacillus sp. could be considered as Bacillus cereus or Bacillus thuringiensis with a bootstrap value of 100% similar to the 16S rRNA gene sequences. The biodegradation capability of the native strains in this study indicates that they have great potential for application in bioremediation of carbofuran-contaminated soil sites.


[Adenocarcinoma of the lung associated with acute promyelocytic leukemia and miliary tuberculosis].
A 44-year-old man was admitted to the hospital because of acute promyelocytic leukemia. A nodular shadow (2.5 cm in diameter) was seen in the right upper lung field on a chest roentgenogram. During the administration of combination chemotherapy for the leukemia, diffuse granular shadow appeared in all lung fields. Transbronchial lung biopsy findings indicated tuberculosis. The patient was given streptomycin, isoniazid, rifampicin and ethambutol, but the nodular show enlarged and a pleural effusion appeared on the right side. Cytologic examination of the pleural effusion revealed adenocarcinoma. Similar findings were obtained from a second transbronchial lung biopsy. The frequency of association of lung cancer and other malignancy is about 4%. The incidences of primary lung cancer found during the course of active tuberculosis, active pulmonary tuberculosis found during the course of primary lung cancer, and tuberculosis found during the course of acute leukemia are 0.9 to 1.4%, 0.4 to 4.3%, and 2.4 to 4.5%, respectively. To our knowledge, this is the first case in Japan in which adenocarcinoma of the lung was associated with acute promyelocytic leukemia and tuberculosis.


Noninvasive three-dimensional electrocardiographic imaging of ventricular activation sequence.
Imaging the myocardial activation sequence is critical for improved diagnosis and treatment of life-threatening cardiac arrhythmias. It is desirable to reveal the underlying cardiac electrical activity throughout the three-dimensional (3-D) myocardium (rather than just the endocardial or epicardial surface) from noninvasive body surface potential measurements. A new 3-D electrocardiographic imaging technique (3-DEIT) based on the boundary element method (BEM) and multiobjective nonlinear optimization has been applied to reconstruct the cardiac activation sequences from body surface potential maps. Ultrafast computerized tomography scanning was performed for subsequent construction of the torso and heart models. Experimental studies were then conducted, during left and right ventricular pacing, in which noninvasive assessment of ventricular activation sequence by means of 3-DEIT was performed simultaneously with 3-D intracardiac mapping (up to 200 intramural sites) using specially designed plunge-needle electrodes in closed-chest rabbits. Estimated activation sequences from 3-DEIT were in good agreement with those constructed from simultaneously recorded intracardiac electrograms in the same animals. Averaged over 100 paced beats (from a total of 10 pacing sites), total activation times were comparable (53.3 +/- 8.1 vs. 49.8 +/- 5.2 ms), the localization error of site of initiation of activation was 5.73 +/- 1.77 mm, and the relative error between the estimated and measured activation sequences was 0.32 +/- 0.06. The present experimental results demonstrate that the 3-D paced ventricular activation sequence can be reconstructed by using noninvasive multisite body surface electrocardiographic measurements and imaging of heart-torso geometry. This new 3-D electrocardiographic imaging modality has the potential to guide catheter-based ablative interventions for the treatment of life-threatening cardiac arrhythmias.


Genetics of fruit body production in higher basidiomycetes II. Monokaryotic and dikaryotic fruiting in schizophyllum commune.
In the wood destroying fungus Schizophyllum commune, a well known subject for genetic studies, fruit bodies are produced not only in the course of the sexual cycle but also asexually. Sexual fruiting requires the establishment of a dikaryon which is under the control of the incompatibility factors A and B. Asexual fruiting, however, starts directly from a monokaryon. The initiation of monokaryotic fruiting requires the presence of a single gene leading to the differentiation of fruit body initials. The action of at least two more genes is required for the further morphogenetic steps resulting eventually in the production of fruit bodies which differ in shape from dikaryotic fruit bodies. As a consequence of a mitosis their basidia produce two spores only. The three genes responsible for monokaryotic fruiting are pleiotropic and determine synergistically the timing of dikaryotic fruiting within a range between 6 to 20 d or longer. A fourth gene was found which codes epistatically for the formation of dome-like masses of stromatic tissue, thus directing morphogenesis into a side track.


Lactate carriers in the artificially perfused human term placenta.
Thirty-two isolated cotyledons from human term placentae were perfused artificially with a tissue culture medium on the maternal and the fetal side. The transfer and uptake of labelled L-lactate and D-lactate (test substance) relative to L-glucose (reference substance, extracellular marker) were investigated in steady-state experiments (n = 9) and in a single passage paired tracer dilution technique (n = 23). The L-lactate transfer exceeded the L-glucose transfer two to three times. The L-lactate uptake into the trophoblast--both from the maternal and the fetal side--was more than three times that of D-lactate. L-lactate transfer and uptake were inhibited by phloretin. The L-lactate transfer showed a saturation kinetic at increasing chemical concentrations of lactate. It is concluded that lactate carriers exist both in the maternal and fetal side of the trophoblast.


An analysis of cancer research funding in the UK.
Until recently, a lack of comparable and reliable data on ongoing research activity has been a significant limiting factor in strategic planning for cancer research. This article describes a new initiative in the UK, which is aimed at facilitating the coordination and strategic planning of cancer research at the national level.


[CONs].
In 2012, USA Preventive Services Task Force revised the guidelines for prostate cancer screening and recommended against prostate specific antigen(PSA)-based screening for prostate cancer for all age groups. This revision had a great impact worldwide. Immediately after the announcement, many expert societies expressed disagreement with this revision, but some of these have gradually come to accept it. When multiple organizations develop guidelines for a particular topic, the recommendations may differ. In this regard, the "standards for developing trustworthy clinical practice guidelines" presented in the report by the Institute of Medicine, will be helpful. The number of cases and the incidence rates of prostate cancer have been rapidly increasing in Japan, especially in the elderly population. Accordingly, sufficient information needs to be provided for appropriate decision-making, considering the balance between the risks and benefits, if cancer screening in the elderly population is to be implemented.


Differences of ploidy status in progression of head and neck melanomas.
Thirty-three common naevi, 26 dysplastic naevi, 58 primary melanomas of facial skin, 24 oral melanomas, 32 lymph nodes and 12 distant melanoma metastases were stained using Feulgen method to evaluate the ploidy status by image analysis GAS-200 system. Eight percent of common naevi, 22% of dysplastic naevi, 43% of facial melanomas, 65% of oral melanomas, 40% of lymph nodes with melanoma metastases and 66% of distant melanoma metastases were classified as aneuploid. In facial melanomas the percentage of aneuploid cases increased with Clark level. Survival time of patients was significantly shorter for aneuploid cases as compared to euploid ones (p <0.01).


Ossification of the ligamentum flavum of the cervical spine.
Ossification of ligamentum flavum (OLF) mainly occurs in the thoracic spine, and rarely in the cervical spine. To clarify its etiology; the features of OLF in the cervical spine were reviewed in 50 reported cases. Age, sex, location of OLF, classification of OLF, radiographic findings, computed tomography (CT) findings, magnetic resonance imaging findings, association of ossification of the posterior longitudinal ligament (OPLL), association of OLF in other spinal regions, and association of diffuse idiopathic skeletal hyperostosis (DISH) were analyzed in 23 detailed cases. Association of OPLL was observed in 7 of 20 cases and 4 of these 7 OPLL cases were at C2-4. Association of OLF in other spinal regions was recognized in 7 of 15 cases. DISH was also present in 3 of 7 cases. Local kyphosis was recognized in 10 of 12 cases by radiography. CT showed facet hypertrophy in 13 of 15 cases and lamina hypertrophy in 14 of 16 cases. Patients with OLF at C2-4 had high rates of local kyphosis and association of hyperostotic state, suggesting both local factors and systemic hyperostotic factors are involved in the formation of OLF of the upper cervical spine. Local factors may be strongly related to the formation of OLF of the middle or lower cervical spine.


Life cycle impact assessment of terrestrial acidification: modeling spatially explicit soil sensitivity at the global scale.
This paper presents a novel life cycle impact assessment (LCIA) approach to derive spatially explicit soil sensitivity indicators for terrestrial acidification. This global approach is compatible with a subsequent damage assessment, making it possible to consistently link the developed midpoint indicators with a later endpoint assessment along the cause-effect chain-a prerequisite in LCIA. Four different soil chemical indicators were preselected to evaluate sensitivity factors (SFs) for regional receiving environments at the global scale, namely the base cations to aluminum ratio, aluminum to calcium ratio, pH, and aluminum concentration. These chemical indicators were assessed using the PROFILE geochemical steady-state soil model and a global data set of regional soil parameters developed specifically for this study. Results showed that the most sensitive regions (i.e., where SF is maximized) are in Canada, northern Europe, the Amazon, central Africa, and East and Southeast Asia. However, the approach is not bereft of uncertainty. Indeed, a Monte Carlo analysis showed that input parameter variability may induce SF variations of up to over 6 orders of magnitude for certain chemical indicators. These findings improve current practices and enable the development of regional characterization models to assess regional life cycle inventories in a global economy.


Evaluation of human viral disease transmission through plasma products.
Alpha's Wet Heat-Treatment process is being applied to both Factor VIII (AHF) and Factor IX Complex (PTC). Twelve hemophilia A, five hemophilia B, and one von Willebrands patient have been followed for at least 6 months for evidence of non-A, non-B hepatitis. No ALT elevations were seen in the hemophilia B patients. There have been four cases of ALT elevation, three in hemophilia A patients and one in the von Willebrand's patient. A subset of these patients have been followed for over one year for anti-HTLV-III status. No patient, either hemophilia A, hemophilia B, or von Willebrand's seroconverted to anti-HTLV-III positive status. Intravenous gamma globulin was studied in 11 normal patients given a single infusion and in 23 immune deficient patients with multiple infusions and evaluations of liver enzymes over a two year period. No elevated ALT or AST values were seen in either group.


Evaluation of Tc-99m-labeled glycoprotein IIb/IIIa receptor antagonist DMP444 SPECT in patients with infective endocarditis.
Infective endocarditis (IE) is characterized by aggregation of activated platelets, fibrin, and bacteria. DMP444, a high-affinity glycoprotein IIb/IIIa receptor antagonist, binds to the fibrinogen-binding domain of activated platelets, depicting a key feature of IE. Tc-99m DMP444 scintigraphy was studied in a group of patients with possible IE. Tc-99m DMP444 (600 MBq; 16 mCi) planar and SPECT images of the heart were recorded in patients with possible IE for as long as 6 hours after injection. Results were compared to echocardiography and the Duke classification. Sixteen patients (age range, 37 to 78 years) participated. DMP444 imaging was positive on SPECT in five patients, and all had definite endocarditis (affecting both prosthetic and native valves). Eleven patients were DMP444 negative, seven with no proof of IE. The remaining four patients were classified as having IE, but three had been receiving adequate intravenous antibiotic regimens for > or = 2 weeks at the time of scintigraphy and one had Q-fever endocarditis. DMP444 SPECT allows in vivo visualization of IE if it is performed within 1 to 2 weeks after the start of antibiotic treatment. Given the high affinity of DMP444 for activated platelets, the results indicate the involvement of activated platelets in early IE.


[Endoluminal, cardiovascular radiotherapy: a new standard].
The treatment for cardiovascular disease, especially the treatment of coronary stenosis, has been continuously improving during the last decades. Routine use of angioplasty was improved by the use of coronary stenting further reducing cardiac morbidity. However, the incidence of restenosis after cardiovascular angioplasty remains high. The restenosis process is mainly explained by neointimal proliferation. Therefore, the utility of ionizing radiation has been systematically investigated in order to reduce proliferation of the neointimal tissue. Radiation therapy turns out to be a very efficient approach in reducing the rate of both de novo lesions as well as of instant restenosis. Recent clinical data from randomized trials confirm the utility of intracoronary radiation therapy and change the treatment standards in interventional cardiology.


Content validity, construct validity, and reliability of the WHOQOL-Bref in a population of Dutch adult psychiatric outpatients.
In this study, the psychometric properties of a quality of life scale, the WHOQOL-Bref, were examined in a population of 533 Dutch adult psychiatric outpatients. Participants underwent two semistructured interviews in order to obtain Axis-I and II diagnoses, according to DSM-IV. Besides the WHOQOL-Bref they also completed questionnaires for measuring psychopathological symptoms (SCL-90) and perceived social support (PSSS). Scores on 25 of the 26 questions of the WHOQOL-Bref had a good distribution. Similar to previous findings, exploratory factor analysis revealed a four-factor structure. A priori expected associations were found between the domains of the WHOQOL-Bref, on the one hand, and dimensions of the SCL-90 and the PSSS-score, on the other hand, indicating good construct validity. The internal consistency of the four domains of the WHOQOL-Bref ranged from 0.66 to 0.80. Domain scores of the WHOQOL-Bref correlated around 0.92 with the WHOQOL-100 domain scores. Relatively low correlations were found between demographic characteristics (age and sex) and WHOQOL-Bref domain scores. It is concluded that the content validity, construct validity, and the reliability of the WHOQOL-Bref in a population of adult Dutch psychiatric outpatients are good. The WHOQOL-Bref, therefore, is an adequate measure for assessing quality of life at the domain level in a population of adult psychiatric outpatients.


Time course of chemotactic factor generation and neutrophil recruitment in the lungs of dust-exposed rats.
The time course of neutrophil recruitment into the lung, neutrophilic chemotactic activity, and the gene expression of neutrophilic chemokines by lavaged cells was determined after intratracheal instillation of various particles. Low-toxicity, low-solubility dusts such as titanium dioxide (TiO2) particles, as well as fibrogenic crystalline silica and nonfibrogenic amorphous silica particles were instilled into the lungs of rats. Results showed that all three dusts induced neutrophilic inflammation as early as 5 h after exposure. Both crystalline and amorphous silica elicited higher degrees of pulmonary inflammation when compared with TiO2 particles. Maximal infiltration of neutrophils into the lungs occurred 5 to 6 h after intratracheal instillation of the dusts. The inflammatory response was transient for TiO2 and amorphous silica, i.e., evident at 2 days after exposure but not different from controls at 10 days after exposure. In contrast, inflammatory effects were sustained through a 10-day period following exposures to crystalline silica. Chemotactic activity for neutrophils was detected directly in bronchoalveolar lavage (BAL) fluids of dust-exposed rats within 2 h after exposure, but not in the BAL fluids of saline- or unexposed rats. The chemotactic activity was correlated with the influx and disappearance of neutrophils into alveolar regions of the lung in TiO2- and amorphous silica-exposed rats. The mRNA expression of two known neutrophil chemotactic cytokines in BAL cells, macrophage inflammatory protein-2 (MIP-2) and KC, also correlated with chemotactic activity and acute and pulmonary inflammatory responses. MIP-2 mRNA was expressed prior to the detection of chemotactic activity in BAL fluids. However, the mRNA expressions of MIP-2 and KC were transient for rats that were exposed to these dusts as KC and MIP-2 message were no longer detectable in BAL cells after 2 days of recovery. Although both neutrophilic chemotactic activity and inflammation remained prominent 10 days after exposure to crystalline silica, MIP-2 expression could not be detected in BAL cells. Thus, we conclude that MIP-2 is likely to be only one of several cytokines involved in mediating neutrophilic inflammation following a single instillation of crystalline silica.


Idiopathic spinal cord herniation associated with calcified thoracic disc extrusion--case report.
A 48-year-old man presented with idiopathic spinal cord herniation associated with calcified thoracic disc extrusion at the T7-8 intervertebral level, manifesting as Brown-Sequard syndrome at the thoracic level persisting for 20 years. Preoperative magnetic resonance imaging and computed tomography myelography revealed ventral displacement of the spinal cord and extrusion of a calcified disc at the T7-8 intervertebral level. At surgery, the spinal cord herniation at this level was released from the dura mater and carefully returned to the dural sac. An extruded calcified thoracic disc was found just below the dural defect at the same level. The development of idiopathic spinal cord herniation is associated closely with a defect in the ventral dura mater of unknown etiology. In our case, the etiology of the ventral dural defect was probably associated with the calcified thoracic disc extrusion.


Ligation of the left renal vein in epm1-Wistar rats: functional and morphologic alterations in the kidneys, testes and suprarenal glands.
The ligation of the left renal vein (LLVR) in man is a controversial procedure in view of the risks of lesion to the renal parenchyma. With the objective of studying the morphologic and functional alterations caused by these lesions, we conducted experimental research with rats. 64 male adult EPM1-WISTAR rats were used, divided into 8 groups-4 for LLRV and four for control. Each LLRV group and corresponding control group were sacrificed progressively on the 7th, 15th, 30th and 60th day after the initial surgery. We found morphofunctional alterations only in animals that underwent LLRV in the four periods of sacrifice. The proteinuria creatinine in serum, testosterone in serum and serum corticosterone in serum showed practically no alteration in relation to the normal values for rats. Statistically significant severe histological lesions were found in the kidneys and testes of the LLRV groups. Lesions in the suprarenal glands were also present in these groups, but no sufficient to demonstrate statistical significance. Based on these results we can conclude that the ligation of the left renal vein is a procedure of high risk in these animals.


Reversible modulation of helicity in a binaphthyl-bipyridinium species and its cucurbit[8]uril complexes.
We describe a tweezer-like molecule constituted of two 4,4'-bipyridinium arms connected by means of alkyl spacers to a 1,1'-binaphthyl unit acting as a hinge. In aqueous solution the twist angle of the binaphthyl can be reversibly modulated by chemical or photochemical reduction of the bipyridinium moieties, and/or addition of cucurbit[8]uril, showing a non-trivial XNOR logic behavior.


Comparison of the cytotoxic impact of chlorfluazuron on selected insect and human cell lines.
To gain new insight into the mechanism of selective cytotoxicity of benzoylureas as insecticides, the in vitro mode of action of chlorfluazuron was investigated on lepidopteran Tn5B1-4 and Sf-21 cells and human Hek293 and HepG2 cells. Chlorfluazuron inhibited the proliferation of Tn5B1-4 and Sf-21 cells with 50% inhibitory concentration values (IC50) of 4.96 µM and 1.12 µM at 48 h and 2.37 µM and 1.76 µM at 96 h, respectively, versus that of Hek293 and HepG2 cells with IC50 values >20 µM. When transferred to chlorfluazuron-free medium, lepidopteran Tn5B1-4 and Sf-21 cells had a postinhibitory recovery development period within 24 h followed by a suppressed increase in cell viability, but human Hek293 and HepG2 cells showed an accelerated increase over their control level. Chlorfluazuron affected Tn5B1-4 and Sf-21 cells, with ≥1.8-fold decreases in the ratio of cellular N-acetylglucosamine (GlcNAc) level and protein content and ≥1.5-fold increases in the mitotic index and G2 /M-phase arrest. Neither Hek293 nor HepG2 cells contained GlcNAc, and chlorfluazuron had no significant effects on the cell cycle and mitotic index of Hek293 and HepG2 cells. In conclusion, the differences between human and lepidopteran cell lines in the characteristic GlcNAc content, G2 /M arrest in the cycle progress, and mitotic index of cells in response to chlorfluazuron may contribute to the selective toxicity of chlorfluazuron to lepidopteran cells.


Korean translation and validation of the functional assessment of cancer therapy-breast (FACT-B) scale version 4.
We undertook to translate and cross-culturally adapt the Functional Assessment of Cancer Therapy-Breast (FACT-B) scale into Korean and to evaluate its reliability and validity. The translation procedure followed the standard Functional Assessment of Chronic Illness Therapy translation methodology. A total of 201 breast cancer patients (mean age, 43.87 years) were studied for psychometric properties of the FACT-B scale. A pre-test of 20 Korean breast cancer patients indicated that the Korean FACT-B scale provided good content coverage and overall comprehensibility. Our results indicated high internal consistency of the FACT-B scale, with Cronbach's alpha coefficients ranging from 0.79 to 0.90. The only exception was the Breast Cancer Scale (BCS), which had a Cronbach's alpha coefficient of 0.67. We can consider that most of the patients in this study had not resumed sexual activity after surgery and found it difficult to comment on this aspect. We also considered that contents of the BCS may have been somewhat heterogeneous. After performing a factor analysis of the BCS data from this study, we identified three factors, accounting 58.8%: psychological distress (5 items, with explained variances of 27.5%), feminine satisfaction (2 items, with explained variances of 17.1%), and physical complaints (2 items, with explained variances of 14.2%). The FACT-B scale also demonstrated good convergent and divergent validity when correlated with the shortened forms of the Profile of Mood States and the Functional Living Index-Cancer (FLIC). We can now evaluate the Quality of Life (QoL) of Korean breast cancer patients using this reliable and valid instrument. Nevertheless our study has the limitation that it did not evaluate the sensitivity to the changes of the patients' QoL in the long term follow-up, and we will supplement it in our further study.


Simultaneous effects of environmental factors on motile Aeromonas dynamics in an urban effluent and in the natural seawater.
Seasonal dynamics of motile Aeromonas in a treated urban effluent and in natural seawater along the Sfax coast (Mediterranean sea, Tunisia) were measured over a year concurrently with seven environmental factors, and compared with those of faecal coliforms. Counts for Aeromonas from a standard plate count method, ranged from 1.48 x 10(5)CFU.100 ml(-1) to 2.2 x 10(8)CFU.100 ml(-1) in the effluent and from 7.9 x 10(3)CFU.100 ml(-1) to undetectable level in the surface marine waters. Contrary to faecal coliforms, the Aeromonas dynamics exhibited a seasonal distribution in seawater which was inverse of the seasonal distribution in the sewage: From the end of November 1998 to April 1999 (cold period), Aeromonas counts increased in the treated effluent, while it decreased very rapidly in seawater. From May to October (warm period), Aeromonas abundance decreased in the effluent but showed an increasing fluctuating trend in the marine waters with a maximum in late summer/early autumn when the temperatures were around 22-23 degrees C. Multiple correlation and regression analyses suggest, by the coefficient of determination (R(2)), that 42% of variance in Aeromonas number changes in the treated effluent, may be explained by only turbidity, radiation and Aeromonas density in the previous sample, while 37% of variance in marine ecosystem were explained by radiance and conductivity. Furthermore, the t statistics and their p values and the coefficient of partial determination (r(2)) indicated that radiance contributed the most (r(2)=0.3184, t=-3.2, p=0.0041) to the dynamics of motile Aeromonas in seawater, when combined with conductivity. The models relevant for changes in faecal coliforms abundance incorporated turbidity, radiance in the effluent and conductivity, pH, radiance, turbidity in coastal marine environment. These models explain 66% and 73% of the observed cell number fluctuation, with turbidity (r(2)=0.529, t=5.08, p=0.0001) and conductivity (r(2)=0.5407, t=4.97, p=0.0001) as dominant factors in the multivariate model proposed, respectively, for the two sampling sites. The results presented here suggest that the combination of negative effects of sunlight and conductivity in natural seawater mainly affects the colony-forming capacity and make the motile Aeromonas nonrecoverable during cold months.


[Endothelial relaxation factor in the development of diabetic nephropathy].
Progression of diabetic nephropathy is now associated with intrarenal hemodynamic disorders (renal hyperperfusion, hyperfiltration, intraglomerular hypertension). The cause of these disorders is unclear. It is supposed that the relaxation factor which is produced by the vascular endothelium (endothelial relaxation factor-ERF) and an endogenous nitrogen oxide (NO) can cause the above intrarenal hemodynamic alterations in diabetes mellitus. The production of ERF/NO in 35 patients with insulin-dependent diabetes mellitus who had varying severities of diabetic nephropathies were examined. These included the following groups: 1) patients without diabetic nephropathy (n = 9); 2) those with incipient diabetes mellitus (n = 12), 3) those with severe diabetes mellitus (n = 14). From groups 1 and 2, 5 patients with hyperfiltration were identified, their glomerular filtration rate were more than 140 ml/ml. The ability of the cells to produce ERF/NO was indirectly estimated, by determining the levels of human platelet guanylate cyclase in the presence of L-arginine, a NO precursor, the accumulation of cGMP in the cells and plasma. When L-arginine was present, the activity of guanylate cyclase was virtually unchanged in Group 1, but it was substantially increased in Groups 2 and 3, by reaching its peak in patients with hyperfiltration (Group 4). The platelet and plasma levels of cGMP corresponded to the enhancement of guanylate cyclase activity in the presence of L-arginine and increased as diabetic nephropathy progressed. Thus, it is suggested that there is ERF/NO hyperproduction in patients at a high risk for diabetic nephropathy (those having hyperfiltration). ERF/NO is likely to promote the dilation of glomerular arterioles, which results in the development of hyperfiltration and intraglomerular hypertension, causing diabetic nephropathy progression.


Inhibition of casein kinase II by dinucleoside polyphosphates.
In our search for potential inhibitors of casein kinase II (CKII) in Artemia, we have shown that dinucleoside polyphosphates are a novel class of effectors for this ubiquitous protein kinase. P1,P4-di(guanosine-5')-tetraphosphate (Gp4G) is a better CKII inhibitor than P1,P4-di(adenosine-5')-tetraphosphate (Ap4A). The inhibition by both effectors is more potent when GTP is used as phosphate donor instead of ATP. The inhibition of CKII increases with the number of phosphates linking the guanosine/adenosine moieties (for n = 2-6). Ap4A does not compete with the protein substrate and causes an increase in the apparent KmATP and a decrease in the apparent VmATP, indicating a mixed type of inhibition with respect to ATP.


[Glial origin of the slow negative potential of the direct cortical response: microelectrode study and mathematical analysis].
Slow negative potential of a direct cortical response is similar in configuration, time-course and reaction to repeated stimuli to depolarization of the cortical glial cells and differs from IPSP of the cortical neurons. According to data of digital spectral (frequency) analysis, slow negative potential is based on the glial component formed by summing up the constituents, which coincide with glial depolarization within a constant factor. The neuronal component, whose contribution is comparatively much smaller, is an indirect result of IPSP.


[Mechanism of hepatocytes transdifferentiation to bile duct epithelial cells and intervention of huangqi decoction].
To investigate the mechanism of hepatocytes transdifferentiation to bile duct epithelial cells (BECs) and intervention of Huangqi decoction (HQD) on hepatic fibrosis formation in rats with secondary cholestasis. Seventy-five SD male rats were made into cholestatic hepatic fibrosis model animals by bile duct ligation, and randomized into the control group (n = 50) and the HQD group (n = 15). Starting from one week after modeling, they were administered orally with saline and HQD respectively for four weeks. Besides, a sham-operated group was set up with 10 rats operated by choledochus segregating only and administered after then with saline. Rats were killed in batches at different time points, i.e. each five from the control group and sham-operated group at the end of the 1st week, five from the control group for each time at the end of the 2nd, 3rd and 4th week, and all the remaining rats at the end of the 5th week. Their liver tissues were taken for histological change examination, content of hydroxyproline (Hyp) determination; protein expression of BECs marker cytokeratin 7 (CK7) and the hepatocyte specific antigen HepPar detection by Western blot, and CK7-Hep Par co-localization by laser confocal microscopy. Then IPP software was used to analyze Sirius red stained positive areas of CK7 and Hep Par, as well as the average IOD of CK7/Hep Par co-localization. Hepatocytes in hepatic tissues (Hep Par positive cell) in the model rats decreased gradually along was time went by after modeling (Sham > M1w > M2w > M3w > M4w > M5w), which was in parallel with the increase of BECs (CK7 positive cells), degree of fibrosis, Hyp content and CK7 protein expression. Increasing of co-localized positive cells of CK7/Hep Par began at 1 week and reached the peak 3 weeks after modeling, then it decreased gradually. The Hep Par protein expression was negatively correlated with that of CK7; the Hep Par positive cell expression was negatively correlated with CK7 positive cell expression and collagen deposition; while the CK7 positive cell expression was positively correlated with the collagen deposition in the liver tissue. Compared with the model control group, the mortality, CK7/Hep Par co-localized positive cells, fibrosis degree, Hyp content and CK7 protein expression were lesser obviously (P < 0.01), while Hep Par positive cell and protein expressions were higher significantly in the HQD group. Hepatocytes transdifferentiation to BECs might be a key pathological element for secondary cholestatic hepatic fibrosis formation; the restraining action of HQD is possibly a major action mechanism of HQD for effectively intervening and treating secondary cholestasis hepatic fibrosis.


Empoderamiento y búsqueda de atención en salud: un factor ignorado de la mortalidad materna en una comunidad indígena mexicana.
Resumen: Objetivo: Indagar la vinculación entre expresiones del empoderamiento (autonomía y poder de decisión) y las prácticas de autocuidado y de búsqueda de atención durante el embarazo y posterior al parto, en relación con la mortalidad materna, en mujeres indígenas del municipio de Santa María Temaxcaltepec, Oaxaca, México. Métodos: se realizaron seis grupos focales: dos con mujeres embarazadas; dos con madres de niños <3 años de edad, y dos con hombres quienes en los últimos tres años fueron padres. Resultados: la hegemonía masculina en el contexto familiar y en las instituciones de salud, dificulta la autonomía y el poder de decisión de las mujeres sobre su salud reproductiva. Esto impacta directamente en la búsqueda de atención durante el embarazo y el parto. Conclusiones: la falta de autonomía y de poder de decisión femenino se relaciona indirectamente, con resultados adversos del embarazo. Estos hallazgos son útiles para orientar el diseño de estrategias que promuevan el empoderamiento de las mujeres y la equidad de género en el contexto de los servicios y programas comunitarios y llamar la atención de tomadores de decisiones hacia la presencia, de factores no-médicos de la muerte materna en comunidades indígenas.


[Organization of the outpatient referral service for patients with disorders of cardiac rhythm and conductivity requiring surgical treatment].
Under analysis were results of the outpatient aid to patients in the center of surgery during 5 years. Every year the consultative and ambulatory aid was given to 1200 patients. A conclusion was made that organization of the city consultative-diagnostic center for patients requiring surgical treatment of arrhythmia with a special staff and equipment for performing electrophysiological and other investigations, organization of the zone consultation units in large polyclinics for electrophysiological investigations will improve the quality and efficiency of treatment of patients with complex disorders of the heart rhythm and conduction.


Atypical resting synchrony in autism spectrum disorder.
Autism spectrum disorder (ASD) is increasingly understood to be associated with aberrant functional brain connectivity. Few studies, however, have described such atypical neural synchrony among specific brain regions. Here, we used magnetoencephalography (MEG) to characterize alterations in functional connectivity in adolescents with ASD through source space analysis of phase synchrony. Resting-state MEG data were collected from 16 adolescents with ASD and 15 age- and sex-matched typically developing (TD) adolescents. Atlas-guided reconstruction of neural activity at various cortical and subcortical regions was performed and inter-regional phase synchrony was calculated in physiologically relevant frequency bands. Using a multilevel approach, we characterized atypical resting-state synchrony within specific anatomically defined networks as well as altered network topologies at both regional and whole-network scales. Adolescents with ASD demonstrated frequency-dependent alterations in inter-regional functional connectivity. Hyperconnectivity was observed among the frontal, temporal, and subcortical regions in beta and gamma frequency ranges. In contrast, parietal and occipital regions were hypoconnected to widespread brain regions in theta and alpha bands in ASD. Furthermore, we isolated a hyperconnected network in the gamma band in adolescents with ASD which encompassed orbitofrontal, subcortical, and temporal regions implicated in social cognition. Results from graph analyses confirmed that frequency-dependent alterations of network topologies exist at both global and local levels. We present the first source-space investigation of oscillatory phase synchrony in resting-state MEG in ASD. This work provides evidence of atypical connectivity at physiologically relevant time scales and indicates that alterations of functional connectivity in adolescents with ASD are frequency dependent and region dependent.


Role of Bismuth in the Electrokinetics of Silicon Photocathodes for Solar Rechargeable Vanadium Redox Flow Batteries.
The ability of crystalline silicon to photoassist the V3+ /V2+ cathodic reaction under simulated solar irradiation, combined with the effect of bismuth have led to important electrochemical improvements. Besides the photovoltage supplied by the photovoltaics, additional decrease in the onset potentials, high reversibility of the V3+ /V2+ redox pair, and improvement in the electrokinetics were attained thanks to the addition of bismuth. In fact, Bi0 deposition has shown to slightly decrease the photocurrent, but the significant enhancement in the charge transfer, reflected in the overall electrochemical performance clearly justifies its use as additive in a photoassisted system for maximizing the efficiency of solar charge to battery.


Novel treatment of Sézary-like syndrome due to adult T-cell leukaemia/lymphoma with daclizumab (humanized anti-interleukin-2 receptor alpha antibody).
We describe a patient with erythrodermic adult T-cell leukaemia/lymphoma resistant to multiple systemic therapies who, on the commencement of daclizumab, a humanized anti-interleukin-2 receptor antibody, developed a rapid and sustained complete response with resolution of previously debilitating erythroderma, suggesting significant activity of this agent in this disease process.


Comparative analysis of specificity in protein-protein interactions. Part I.: A theoretical and mathematical approach to specificity in protein-protein interactions.
The definition of informational complementarity (IC) is introduced and a comparative computer method is described to analyse the possible sources of the specificity in some protein-protein (P-P) interactions. The essence of this method is the step-by-step comparison of the primary structures of the proteins regarding the frequency and sequence (distribution) of one or more selected amino acids. The calculation of the probability of finding two different amino acids in two different protein parts by the same frequency and distribution (Random Pair Building, RPB) and it's checking with the number of actually found pairs (Concrete Pair Building, CPB) and with the number of maximal available pair forming (Maximal Pair Building, MPB) may give the chance to find IC sequences and to understand the nature of specific P-P interactions. The usefulness of this method for analysing intramolecular structures and intermolecular interactions is discussed and an example is presented how it may be used.


One electron oxidation of triferrocenylmethanol: synthesis, metal atom dynamics, electron delocalization, and the crystal structure of [Fc3COH](+) PF6⁻.
The title compound 2 was prepared and its crystal structure was determined at 100 K. The neat solid was examined by temperature dependent (57)Fe Mössbauer effect (ME) spectroscopy over the interval 92 < T < 318 K, and evidences two diamagnetic Fe(II) sites and one paramagnetic Fe(III) site. The latter shows spin-lattice relaxation, but there is no evidence of electron delocalization among the three iron sites in the above temperature interval. The mean-square-amplitude-of-vibration of the diamagnetic iron site has been determined from the recoil-free fraction ME resonance, and compared to the neutral Fc(3)COH homologue (1). The ME dynamical data are in good agreement with the U(i,j) value at 100 K extracted from the crystallographic results. The ME parameters at 5 K have also been determined with the sample compound embedded in a paraffin wax matrix as well as pelletized with BN.


WITHDRAWN: Single-dose del Nido cardioplegia in minimally invasive aortic valve surgery.
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The phosphodiesterase 5 inhibitor tadalafil regulates lipidic homeostasis in human skeletal muscle cell metabolism.
Tadalafil seems to ameliorate insulin resistance and glucose homeostasis in humans. We have previously reported that tadalafil targets human skeletal muscle cells with an insulin (I)-like effect. We aim to evaluate in human fetal skeletal muscle cells after tadalafil or I: (i) expression profile of I-regulated genes dedicated to cellular energy control, glycolitic activity or microtubule formation/vesicle transport, as GLUT4, PPARγ, HK2, IRS-1, KIF1C, and KIFAP3; (ii) GLUT4, Flotillin-1, and Caveolin-1 localization, all proteins involved in energy-dependent cell trafficking; (iii) activation of I-targeted paths, as IRS-1, PKB/AKT, mTOR, P70/S6K. Free fatty acids intracellular level was measured. Sildenafil or a cGMP synthetic analog were used for comparison; PDE5 and PDE11 gene expression was evaluated in human fetal skeletal muscle cells. RTq-PCR, PCR, western blot, free fatty acid assay commercial kit, and lipid stain non-fluorescent assay were used. Tadalafil upregulated I-targeted investigated genes with the same temporal pattern as I (GLUT4, PPARγ, and IRS-1 at 3 h; HK2, KIF1C, KIFAP3 at 12 h), re-localized GLUT4 in cell sites positively immune-decorated for Caveolin-1 and Flotillin-1, suggesting the involvement of lipid rafts, induced specific residue phosphorylation of IRS-1/AKT/mTOR complex in association with free fatty acid de novo synthesis. Sildenafil or GMP analog did not affect GLUT4 trafficking or free fatty acid levels. In human fetal skeletal muscle cells tadalafil likely favors energy storage by modulating lipid homeostasis via IRS-1-mediated mechanisms, involving activation of I-targeted genes and intracellular cascade related to metabolic control. Those data provide some biomolecular evidences explaining, in part, tadalafil-induced favorable control of human metabolism shown by clinical studies.


Characterisation and functional properties of watermelon (Citrullus lanatus) seed proteins.
People in developing countries depend largely on non-conventional protein sources to augment the availability of proteins in their diets. Watermelon seed meal is reported to contain an adequate amount of nutritional proteins that could be extracted for use as nutritional ingredients in food products. Osborne classification showed that globulin was the major protein (≥500 g kg (-1)) present in watermelon seed meal, followed by albumin and glutelin. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that the polypeptides had low molecular weights ranging from 35 to 47 kDa. Isoelectric focusing revealed that the isoelectric point of most proteins was in the acidic range 4-6. These proteins are rich in aspartic acid, glutamic acid and serine. An increase in pH (5-9) significantly (P < 0.05) decreased the denaturation enthalpy of these proteins. Among functional properties, albumin exhibited a much higher dispersibility index (810.3-869.6 g kg(-1)) than globulin (227.8-245.4 g kg(-1)), glutelin (182.1-187.7 g kg(-1)) and prolamin (162.3-177.7 g kg(-1)). Digestibility was in the ranges 760.6-910.0 and 765.5-888.5 g kg(-1) for Mateera and Sugar Baby watermelon protein fractions respectively, while surface hydrophobicity ranged from 126.4 to 173.2 and from 125.8 to 169.3 respectively. The foaming and emulsifying properties of albumin were better than those of the other proteins studied. The good nutritional and functional properties of watermelon seed meal proteins suggest their potential use in food formulations.


Comparative performance of Aspergillus galactomannan ELISA and PCR in sputum from patients with ABPA and CPA.
Galactomannan (GM) and Aspergillus DNA detection are useful tools for the diagnosis of invasive pulmonary aspergillosis (IPA), primarily in blood and bronchoscopy samples. This study aimed to evaluate the utility of both markers for detection of Aspergillus in sputum from patients with allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). ABPA or CPA demographic patient data were retrieved. This retrospective observational audit included 159 patients with at least one sputum pair. 223 sputum sample pairs were analysed, as well as six control samples for GM only. Real time PCR was performed following sputum DNA extraction using the MycAssay™ Aspergillus kit and cycle thresholds were subtracted from 38 to give positive values (transformed Ct, TCt). The mean age of the patients was 61.81years (SD: ±11.06; range 29-100). One hundred and twenty-six (79.2%) had CPA. Cultures were positive for fungi in 13.1% of the samples, and A. fumigatus was the commonest (11.9%) fungus isolated. Receiver operating characteristic (ROC curve) analysis of sputum GM comparing TCt of >0.0, and >2.0 to derive GMI cut-off values showed a cut-off of 6.5. About 50% of sputa with strongly positive PCR values had GM values>6.5. Two of six (33%) control samples had GM indices>6.5. It is not clear that GM determinations in sputum are useful for diagnosis of either CPA or ABPA, or following therapy.


Hydrogenated uniform Pt clusters supported on porous CaMnO(3) as a bifunctional electrocatalyst for enhanced oxygen reduction and evolution.
Hydrogenated uniform Pt clusters supported on porous CaMnO3 nanocomposites are synthesized and investigated as a new electrocatalytic material for oxygen reduction and evolution reactions. Due to the synergistic effect of Pt and CaMnO3, the nanocomposites exhibit superior activity and durability to the benchmark Pt/C catalyst.


Elongated silica nanoparticles with a mesh phase mesopore structure by fluorosurfactant templating.
Mesoporous silica materials with pore structures such as 2D hexagonal close packed, bicontinuous cubic, lamellar, sponge, wormhole-like, and rectangular have been made by using surfactant templating sol-gel processes. However, there are still some "intermediate" phases, in particular mesh phases, that are formed by surfactants but which have not been made into analogous silica pore structures. Here, we describe the one-step synthesis of mesoporous silica with a mesh phase pore structure. The cationic fluorinated surfactant 1,1,2,2-tetrahydroperfluorodecylpyridinium chloride (HFDePC) is used as the template. Like many fluorinated surfactants, HFDePC forms intermediate phases in water (including a mesh phase) over a wider range of compositions than do hydrocarbon surfactants. The materials produced by this technique are novel elongated particles in which the layers of the mesh phase are oriented orthogonal to the main axis of the particles.


Prevention of hypertension, hyperglycemia and vascular oxidative stress by aspirin treatment in chronically glucose-fed rats.
To examine whether an in vivo chronic treatment with aspirin could prevent insulin resistance, oxidative stress and blood pressure elevation associated with high glucose feeding in rats. Sprague-Dawley rats (SD) were given a normal chow diet for 3 weeks combined or not with a 10% glucose drinking solution with or without aspirin added to their drinking water, and were compared to control SD rats which received normal chow and tap water to drink for 3 weeks. Oxidative stress was evaluated by measuring superoxide anion (O2-) production in the aorta using the lucigenin-enhanced chemiluminescence method. Antioxidant reserve was assessed by measuring the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the blood. Fasting blood sugar and insulin levels were measured at the end of the study. The systolic blood pressure (SBP), the aortic basal superoxide production, plasma levels of insulin and glucose, as well as the insulin resistance index, were all significantly higher in rats fed glucose for 3 weeks, compared to control rats. The simultaneous treatment with aspirin prevented the increase in SBP, in plasma glucose levels and in aortic O2- production, and attenuated the rise in insulin levels as well as insulin resistance in the glucose-fed rats. Positive correlations between aortic O2- production and SBP, as well as between insulin resistance and SBP or between O2- production and insulin resistance, were found in control, glucose-fed and aspirin-treated, glucose-fed rats. The activities of GPx and SOD in the erythrocytes did not differ in the three groups. An increase in plasma SOD activity was observed in glucose-fed rats. Chronic in vivo treatment with aspirin prevented the development of hypertension and reduced insulin resistance significantly in chronically glucose-fed rats. Aspirin seems to produce these effects through its antioxidative properties, since it was found to prevent the increase in aortic O2- production observed in chronically glucose-fed rats.


Production of recombinant human apoferritin heteromers.
We are interested in learning how iron is safely inserted and stored in ferritin. Recombinant DNA technology has considerable potential in determining the functional roles of the two ferritin subunits (H and L). In previous studies, we have observed that recombinant rat H ferritin was repressive to cell growth in both prokaryotic and eukaryotic expression systems (Guo et al., Biochem. Biophys. Res. Commun. 242, 39-45 (1998)). This results in the protein being expressed at very low levels. This problem was partially bypassed by the use of an inducible expression system, which utilizes T7 RNA polymerase dependent expression of the gene, induced by isopropyl beta-D-thiogalactopyranoside (IPTG). Simultaneously expressing the H and L ferritin genes in this system resulted in only a narrow range of ferritin heteromers, which predominantly consisted of the L subunit. Addition of rifampicin to cultures, 1 h following the induction of protein synthesis by IPTG, increased the production of the H subunit and thus increased the range of ferritin H:L subunit ratios. Simultaneous expression of the H and L ferritin genes in Escherichia coli grown in a deficient medium with minimal iron and with the addition of rifampicin resulted in the production of a range of recombinant human apoferritin heteromers that could be separated based on their subunit composition.


[Osteomalacia and its development in patients after stomach resection].
An examination was performed in 15 patients who had developed pronounced osteomalacia following gastric resection. The discussion covers potential pathogenetic mechanisms responsible for bone tissue metabolism disorders and approaches to correction thereof.


Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease.
Huntington's disease (HD) is a progressive neurological disease characterised by motor dysfunction, cognitive impairment and personality changes. Previous work in HD patients and animal models of the disease has also highlighted retinal involvement. This study characterised the changes in retinal structure and function early within the progression of disease using the R6/1 mouse model of HD. The retinal phenotype was observed to occur at the same time in the disease process as other neurological deficits such as motor dysfunction (by 13 weeks of age). There was a specific functional deficit in cone response to the electroretinogram and using immunocytochemical techniques, this dysfunction was found to be likely due to a progressive and complete loss of cone opsin and transducin protein expression by 20 weeks of age. In addition, there was an increase in Müller cell gliosis and the presence of ectopic rod photoreceptor terminals. This retinal remodelling is also observed in downstream neurons, namely the rod and cone bipolar cells. While R6/1 mice exhibit significant retinal pathology simultaneously with other more classical HD alterations, this doesn't lead to extensive cell loss. These findings suggest that in HD, cone photoreceptors are initially targeted, possibly via dysregulation of protein expression or trafficking and that this process is subsequently accompanied by increased retinal stress and neuronal remodelling also involving the rod pathway. As retinal structure and connectivity are well characterised, the retina may provide a useful model tissue in which to characterise the mechanisms important in the development of neuronal pathology in HD.


Accuracy of float testing for metered-dose inhaler canisters.
To characterize and evaluate canister floating patterns of three commercially available metered-dose inhalers (MDIs) with varying amounts of medication remaining. Four canisters each of three asthma medications were studied. MDIs were actuated every 30 seconds to 60 seconds, and canisters were weighed and floated at 100%, 75%, 66%, 50%, 33%, 25%, 10%, and 0% of remaining labeled actuations. Position of the canisters and percentage submersion in water were recorded. Controlled laboratory. We observed differences among the products with regard to canister floating behavior at varying levels of fullness. All canisters were completely submerged with the nozzle up at two-thirds full and greater. The canisters remained nozzle-up and were submerged to varying levels at the half-full point. When observed at less than half full, canisters inverted and floated nozzle down. Positions of the canisters varied among products at less than half full. No canister was fully tilted when all labeled actuations were used. Float characteristics are product-specific and a function of canister size, design, content, and method of testing. Clinicians and asthma educators should not advise patients to use a float test to assess the amount of medication remaining in an MDI. Recommendations from the National Asthma Education and Prevention Program of the National Heart, Lung, and Blood Institute suggest that the only reliable method for determining the number of doses remaining in a canister is to subtract the number of doses used from the number available.


A quality monitoring program for red blood cell components: in vitro quality indicators before and after implementation of semiautomated processing.
Canadian Blood Services has been conducting quality monitoring of red blood cell (RBC) components since 2005, a period spanning the implementation of semiautomated component production. The aim was to compare the quality of RBC components produced before and after this production method change. Data from 572 RBC units were analyzed, categorized by production method: Method 1, RBC units produced by manual production methods; Method 2, RBC units produced by semiautomated production and the buffy coat method; and Method 3, RBC units produced by semiautomated production and the whole blood filtration method. RBC units were assessed using an extensive panel of in vitro tests, encompassing regulated quality control criteria such as hematocrit (Hct), hemolysis, and hemoglobin (Hb) levels, as well as adenosine triphosphate, 2,3-diphosphoglycerate, extracellular K(+) and Na(+) levels, methemoglobin, p50, RBC indices, and morphology. Throughout the study, all RBC units met mandated Canadian Standards Association guidelines for Hb and Hct, and most (>99%) met hemolysis requirements. However, there were significant differences among RBC units produced using different methods. Hb content was significantly lower in RBC units produced by Method 2 (51.5 ± 5.6 g/unit; p < 0.001). At expiry, hemolysis was lowest in Method 2-produced RBC units (p < 0.05) and extracellular K(+) levels were lowest in units produced by Method 1 (p < 0.001). While overall quality was similar before and after the production method change, the observed differences, although small, indicate a lack of equivalency across RBC products manufactured by different methods.


Sinking during earthquakes: Critical acceleration criteria control drained soil liquefaction.
This article focuses on liquefaction of saturated granular soils, triggered by earthquakes. Liquefaction is defined here as the transition from a rigid state, in which the granular soil layer supports structures placed on its surface, to a fluidlike state, in which structures placed initially on the surface sink to their isostatic depth within the granular layer. We suggest a simple theoretical model for soil liquefaction and show that buoyancy caused by the presence of water inside a granular medium has a dramatic influence on the stability of an intruder resting at the surface of the medium. We confirm this hypothesis by comparison with laboratory experiments and discrete-element numerical simulations. The external excitation representing ground motion during earthquakes is simulated via horizontal sinusoidal oscillations of controlled frequency and amplitude. In the experiments, we use particles only slightly denser than water, which as predicted theoretically increases the effect of liquefaction and allows clear depth-of-sinking measurements. In the simulations, a micromechanical model simulates grains using molecular dynamics with friction between neighbors. The effect of the fluid is captured by taking into account buoyancy effects on the grains when they are immersed. We show that the motion of an intruder inside a granular medium is mainly dependent on the peak acceleration of the ground motion and establish a phase diagram for the conditions under which liquefaction happens, depending on the soil bulk density, friction properties, presence of water, and peak acceleration of the imposed large-scale soil vibrations. We establish that in liquefaction conditions, most cases relax toward an equilibrium position following an exponential in time. We also show that the equilibrium position itself, for most liquefaction regimes, corresponds to the isostatic equilibrium of the intruder inside a medium of effective density. The characteristic time to relaxation is shown to be essentially a function of the peak ground velocity.


New perspectives in long-term outcomes in clinical trials of pulmonary arterial hypertension.
The past two decades have seen significant improvements in the management of patients with pulmonary arterial hypertension (PAH). Although outcome has improved, long-term prognosis remains unsatisfactory. The development of new treatment options is clearly important. Equally important is testing new agents in trials designed to provide robust evidence for sustained clinical benefits enabling clinicians to determine the optimal treatment strategy for individual patients. End-points such as the change in 6-min walk distance (6MWD) have been pivotal in the registration trials of currently available PAH-specific therapies. However, as current clinical trials enrol patients with milder disease, many already on background therapy, there is growing evidence that change from baseline in 6MWD is a weak surrogate of outcome in PAH. In addition, while short-term trials allowed for the rapid approval of PAH therapies in the past, there is increasing recognition that clinical trials for new agents must provide evidence of long-term benefits. Clinical trials need to evolve to provide the long-term, clinically relevant data required to appropriately assess new therapies. Event-driven long-term morbidity and mortality trials are currently underway, and will provide robust data on the frequency and timing of events, and are likely to reflect the future of clinical trial design in PAH.


The modern matron: a hybrid management role with implications for continuous quality improvement.
This paper describes the second phase of a research study into the introduction of the 'modern matron' role in the National Health Service. It draws on information from a survey of modern matrons in 10 case study trusts and from semistructured interviews with purposively selected matrons and their key contacts. Three models of role implementation are identified, each typical of 'hybrid management' but with different emphases on matrons' professional (clinical) and corporate management responsibilities. There is evidence that matrons are starting to make an impact on different aspects of quality improvement in their trusts, but this is often limited by lack of forethought about where they should be located in the organization. It is suggested that, before making decisions about establishing modern matron posts, trusts need to have a clearer understanding both of the different contributions matrons can make to quality improvement and the challenges posed by this type of role.


ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.
To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.


The kidney in the fetal rat model of congenital diaphragmatic hernia induced by nitrofen.
This paper explores whether there is a correlation between kidney and lung growths in an experimental model of congenital diaphragmatic hernia (CDH) induced by intragastric administration of Nitrofen (115 mg/kg) in olive oil on time-dated pregnant Wistar rats at the 9th day of gestation. For comparison we used pregnant rats treated with olive oil alone. Twenty-nine normal fetuses from 3 control rats and 24 left CDH fetuses from 6 Nitrofen rats were studied. Fetal (3.6 +/- 0.8 v 4.9 +/- 0.4 g, P < .001) and total lung (2% +/- 0.5% v 2.6% +/- 0.3% of body weight, P < .001) weights were significantly decreased in animals with CDH. Kidneys were also smaller in CDH animals although not significantly (0.7% +/- 0.1% v 0.8% +/- 0.1% of body weight, P = .05) and were also histologically immature. Regression of kidney weight on body weight for both groups yielded regression lines that were identical at analysis of covariance and all data points from the CDH group were within the control group 95% confidence limits. After converting raw data into lung/body and kidney/body weight ratios, no inverse correlation suggesting a feedback mechanism of growth regulation between both organs could be found. Since nitrofen acts through modifications of the thyroid hormone status in both dam and fetus, altered maturation of several organs should be expected although some of them, like the lung, are the leading targets. The present CDH rodent model is probably different from the human malformation in spite of the striking anatomic similarities between them.(ABSTRACT TRUNCATED AT 250 WORDS)


Radiological and pulmonary function outcomes of children with SARS.
We examined the radiological and pulmonary function outcomes of children affected with severe acute respiratory syndrome (SARS) at 6 months from diagnosis. Twenty-one female and 26 male Chinese patients (median age, 13.6 years; interquartile range, 9.9-16.0) were studied. In each subject, high-resolution computed tomography (HRCT) of the thorax and pulmonary function were assessed. All children were asymptomatic and had a normal clinical examination. Mild pulmonary abnormalities were detected on HRCT in 16 (34.0%) subjects, including residual ground-glass opacification (n = 5), air trapping (n = 8), and a combination of ground-glass changes and air trapping (n = 3). The need for oxygen supplementation (P = 0.02) and lymphopenia during the course of illness (P = 0.012) were significant risk factors in predicting abnormal HRCT. There were no significant lung function differences between those with and without HRCT abnormalities. Despite complete clinical resolution, a considerable proportion of children affected with SARS had abnormal HRCT findings at 6 months. These abnormalities were more prevalent in those with severe disease. It is important that careful follow-up be carried out to assess the clinical significance and persistence of such abnormalities.


Prevention of TCDD toxicity in laboratory rodents by addition of charcoal or cholic acids to chow.
The mortalities of mice, rats and guinea-pigs given a single lethal dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were substantially reduced by feeding them with chows containing 2.5 or 5% activated charcoal, which presumably enhances elimination of the toxic agent from the organism. Chows with 0.25 or 0.5% cholic acid and dehydrocholic acid added had a similar protective action on mice intoxicated with TCDD. Since no treatment is currently available for this type of poisoning, charcoal-whose safe clinical use is well established-is worth considering in view of its potential benefit to humans acutely exposed to TCDD.


Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells.
Heat shock protein 27 (Hsp27) is a cytoprotective chaperone that is phosphoactivated during cell stress that prevents aggregation and/or regulate activity and degradation of certain client proteins. Recent evidence suggests that Hsp27 may be involved in tumor progression and the development of treatment resistance in various tumors, including bladder cancer. The purpose of this study was to examine, both in vitro and in vivo, the effects of overexpression of Hsp27 and, correspondingly, the down-regulation of Hsp27 using small interfering (si) RNA and OGX-427, a second-generation antisense oligonucleotide targeting Hsp27. Hsp27 overexpression increased UMUC-3 cell growth and resistance to paclitaxel. Both OGX-427 and Hsp27 siRNA decreased Hsp27 protein and mRNA levels by >90% in a dose- and sequence-specific manner in human bladder cancer UMUC-3 cells. OGX-427 or Hsp27 siRNA treatment induced apoptosis and enhanced sensitivity to paclitaxel in UMUC-3 cells. In vivo, OGX-427 significantly inhibited tumor growth in mice, enhanced sensitivity to paclitaxel, and induced significantly higher levels of apoptosis compared with xenografts treated with control oligonucleotides. Collectively, these findings suggest that Hsp27 knockdown with OGX-427 and combined therapy with paclitaxel could be a novel strategy to inhibit the progression of bladder cancer.


The human physiome as an information environment.
Modern biology is rapidly laying the foundation necessary for integrated modeling of physiological processes in living organisms. The human physiome project attempts to model interactions between biochemicals, cellular organelles, cells, tissues, and organs within whole organisms. One of the first challenges that this project faces is the development of a database environment flexible enough to accommodate the diversity in structure and content of physiological data. This paper reviews the current state of database technology, presents our understanding of the physiome database problem, and proposes a preliminary strategy for addressing it.


Stromal-cell-derived factor-1/CXCL12-induced chemotaxis of a T cell line involves intracellular signaling through Cbl and Cbl-b and their regulation by Src kinases and CD45.
Stromal-cell-derived factor-1alpha (SDF-1alpha/CXCL12) is a potent chemoattractant for T cells. We report that Cbl family members, Cbl and Cbl-b, are tyrosine-phosphorylated after SDF-1alpha/CXCL12 stimulation of Jurkat T cells. Enhanced phosphorylation of Cbl and Cbl-b was regulated by src family kinases, and perhaps Fyn. Activated Cbl and Cbl-b interacted with Crk-L, Zap-70, Nck, PLC-gamma and Fyb after SDF-1alpha/CXCL12 stimulation, implicating association of these proteins in SDF-1alpha/CXCL12 actions. SDF-1alpha/CXCL12 did not induce tyrosine phosphorylation of Cbl or Cbl-b in Lck-deficient T cell line J.CaM1.6 or CD45-deficient T cell line J45.01. Thus, Lck Src kinase and tyrosine phosphatase CD45 are likely involved in regulating activation of Cbl family members. A functional role for Cbl and Cbl-b in migration was demonstrated by the decrease in SDF-1/CXCL12-induced migration in a T cell line in which transfected small interfering RNA for Cbl and Cbl-b decreased expression of Cbl and Cbl-b, but not MAPK activity. SDF-1alpha/CXCL12-induced chemotaxis was greatly reduced in the CD45-deficient T cell line. Our results implicate CD45, Cbl, Cbl-b, src kinases and potentially other associated proteins as mediators of SDF-1alpha/CXCL12-induced cell migration of Jurkat T cells.


Myeloperoxidase deficiency: prevalence and clinical significance.
Leukocyte differential counting by flow cytochemistry has shown 28 subjects with partial or complete neutrophil myeloperoxidase (MPO) deficiency in a population of about 60 000 patients screened at a general hospital. Partial (13 patients) or complete (13 patients) MPO deficiency was confirmed by examination of cytochemical stains in 26, biochemical measurement of total enzymatic activity in eight, and flow cytometry in six patients. None had apparent hematologic disorders. Only four patients had infections; of these, two had major systemic infections (one, candidiasis; one, bacteremia). In assays of leukocyte function only minor defects in killing of Staphylococcus aureus by MPO-deficient cells were noted whereas killing of Candida albicans was much more impaired. Family studies in eight patients have shown various degrees of partial or complete MPO deficiency in first-degree relatives of six. The findings indicate that the incidence of MPO deficiency is much higher than previously suspected. Although MPO appears to be necessary for killing of Candida species by neutrophils, the importance of its role in normal antibacterial defense must be re-evaluated.


Interaction of molybdate with copper(II)-histidine.
Molybdate and copper(II)-histidine form an insoluble complex of empirical formula Cu2(His)3(MoO4)2(H2O)2ESR-spectroscopy indicated that the complex had tetragonal symmetry. IR-spectroscopy showed the presence of a carboxylate anion and suggested that the molybdate ion formed an ammonium-type salt with the nitrogens of the imidazole. The complex did not form following dissociation of the protonated imidazole (above a pH of approximately 6).


What does it take to cope with the pressures of work?
Nursing leaders are always busy. Balancing pressures, demands and responsibilities is part of their work. How effectively they can cope is often described as how resilient they are.