The expression patterns of standard and variant CD44 molecules in normal uterine cervix and cervical cancer.
CD44 is a cell-surface glycoprotein postulated to play a role in tumor-cell metastasis. We have examined the expression of the standard CD44 (CD44s), and alternative spliced variants of CD44 containing variant exons v6, v9, and v1O (CD44v6, CD44v9, and CD44v10 respectively) in 9 samples of normal cervix, 6 samples of cervical intraepithelial neoplasia (CIN), and 11 samples with invasive cervical carcinomas. RT/PCR demonstrated the presence of CD44s in all samples of normal cervix and those with invasive carcinomas. CD44v6 was also found in all normal cervical samples and in 9 tissue samples of invasive carcinomas. The results also suggested that some tumor specimens had several higher molecular transcripts containing exon v6 compared to specimens of normal cervix. Immunohistochemistry detected the presence of CD44s and the absence of CD44v10 in both epithelial and stromal cells in all specimens. In contrast, CD44v6 and CD44v9 were stained positive in epithelial cells but were absent in stromal cells. The intensity of CD44v6 and CD44v9 staining was strongest in normal cervical epithelium followed by CIN, invasive squamous cell carcinoma, and adenocarcinoma. In the malignant samples, heterogeneity in staining intensity among different clusters of tumor cells was observed. Furthermore, poorly differentiated and undifferentiated carcinomas from patients having poor prognosis did not stain at all. This study suggests that variant CD44 molecules may serve an important function in the cell contact of cervical epithelial cells, and that cervical epithelium acquires heterogeneity in the expression of CD44 adhesion molecules during carcinogenesis, which may be related to tumor metastasis.


[Research progress of construction of tissue engineered osteochondral composites].
To review the recent progress of the researches in construction of tissue engineered osteochondral composites, and to discuss the challenges in construction of tissue engineered osteochondral composites. The recent literature on the construction of tissue engineered osteochondral composites was extensively reviewed and analyzed. The studies on the construction of tissue engineered osteochondral composites are relatively more in vivo, the current focus is that different tissues derived mesenchymal stem cells are widely used to be seed cells; single-phase scaffold has been limited, studies on biphase scaffold and triphase scaffold are new trends; the design and performance of bioreactor need to be further optimized in the future. The construction of tissue engineered osteochondral composites will be a promising method for the treatment of cartilage defects.


[Selection of the method of renal revascularization in arteriosclerosis of the renal arteries].
The work has analyzed results of 91 transaortal endarterectomies and 66 prostheses of renal arteries with the autovein. A preliminarily arterialized autovein is proposed as an autotransplant. The arterialization is achieved by inclusion of the autovein in the peripheral arterial system where the vein is gradually transformed and within 10-12 weeks its structure and biomechanical properties become closer to those of the artery of the musculo-elastic type. Preliminary arterialization excludes dilatatory changes of the autovenous transport.


Bilateral posterior scleritis: an idiopathic painless presentation.
To describe a presentation of painless posterior scleritis. This study was an interventional case report. An 18-year-old boy was admitted to the authors' clinic with symptoms of low degree of vision and no ocular pain. Ophthalmologic examination, ocular ultrasonography, magnetic resonance imaging, fundus fluorescein angiography (FFA), optical coherence tomography (OCT), thoracic radiography, abdominal sonography, and laboratory testing were carried out and the results were evaluated. OCT revealed bilateral exudative retinal detachment. Diffuse bilateral posterior scleral thickening and serous retinal detachment were found in B-scan ultrasonography, suggesting posterior scleritis. Laboratory findings and imaging disclosed no systemic disease. The patient responded to oral prednisolone 60 mg once daily. The case reported here indicates that pain is not always present in posterior scleritis.


[Morphometric study of transitional carcinoma of the bladder (I): analysis of 148 superficial tumors].
A morphometric study of the tumor cell nucleus was performed in 148 cases of superficial transitional cell carcinoma of the bladder. Of these, 131 were papillary and 17 were nonpapillary tumors. Our methodology is compared with those described elsewhere. With regard to papillary tumors, the nuclear size of the internal papilla near the stroma was found to be greater than that of the external papilla near the bladder lumen. Tumor cells with internal papillary nuclear size less than or equal to 28 microns 2 appeared to have a better prognosis. Thus, nuclear measurements in this area must be performed in future studies. No conclusive data could be obtained relative to the nonpapillary tumors. For both papillary and nonpapillary tumors, the higher the histologic grade, the greater the nuclear size, the differences being statistically significant.


Feelings of Disenfranchisement and Support Needs Among Patients With Thyroid Cancer.
To offer a better understanding of the experiences, preferences, and needs of patients with thyroid cancer. 17 patients with thyroid cancer receiving treatment at a university-affiliated hospital in Montreal, Québec, Canada. Interviews were conducted with patients, and descriptive phenomenology was used to explore patients' lived experience. Coping with uncertainty was a major theme that emerged from interviews, with some of the main concerns being difficult treatment decisions, long surgery wait times, and fears about surgical complications, potential metastases, and death. Study participants reported that without a nurse and an interprofessional team, they would be lost in a system they believed minimized their illness and offered few resources to support them in a time of crisis. Nurses must understand how the needs of individuals with thyroid cancer are often overlooked because of the good prognosis associated with the disease and should work to meet these information and support needs.


Oral cancer awareness and knowledge among dental patients in South India.
To assess the 1) levels of awareness and knowledge about risk factors and early signs of oral cancer among dental patients visiting dental hospital in Hyderabad city, South India 2) and to correlate the knowledge levels according to age, gender and education levels. The survey comprised of 16-item questionnaire which was distributed to patients attending Panineeya Institute of Dental Sciences, Hyderabad. Data was collected and statistically analysis was done using SPSS software (12.0 version). p<0.05 was considered statistically significant. 2045 participants completed the questionnaire (response rate - 97. 9%). The reliability of the questionnaire as calculated by Cronbach's alpha was 0.75. Mean age of the study population was 37.9 years. 60.2% of the respondents had heard about oral cancer. When knowledge towards risk factors of oral cancer was taken into consideration along with variables, significant differences were seen only in gender with female having better knowledge (p=0.02). No significant difference was noted among the age group and varying education levels. However, knowledge about early signs of oral cancer revealed a highly significant difference with the level of education (p=0.000). The awareness levels and knowledge about risk factors and early signs of oral cancer in this cross-section of Indian dental patients were satisfactory.


Highly efficient detoxification of Cr(VI) by chitosan-Fe(III) complex: process and mechanism studies.
Metal-biopolymer complexes has recently gained significant attention as an effective adsorbent used for the removal of Cr(VI) from water. Unfortunately, despite increasing research efforts in the field of removal efficiency, whether this kind of complex can reduce Cr(VI) to less-toxic Cr(III) and what are the mechanisms of detoxification processes are still unknown. In this study, despite the highly adsorption efficiency (maximum adsorption capacity of 173.1 mg/g in 10 min), the significant improvement of Cr(VI) reduction by chitosan-Fe(III) complex compared with normal crosslinked chitoan has been demonstrated. In addition, the structure of chitosan-Fe(III) complex and its functional groups concerned with Cr(VI) detoxification have been characterized by the powerful spectroscopic techniques X-ray absorption fine structure (XAFS) and X-ray photoelectron spectroscopy (XPS). The XPS spectra indicated that the primary alcoholic function on C-6 served as an electron donor during Cr(VI) reduction and was oxidized to a carbonyl group. The X-ray adsorption near edge spectra (XANES) of the Cr(VI)-treated chitosan-Fe(III) complex revealed the similar geometrical arrangement of Cr species as that in Cr(III)-bound chitosan-Fe(III). Overall, a possible process and mechanism for highly efficient detoxification of Cr(VI) by chitosan-Fe(III) complex has been elucidate.


The neurophysiology of hydrogen sulfide.
Hydrogen sulfide (H(2)S) has emerged as the third endogenous gaseous mediator in the central and peripheral nervous system. H(2)S is generated by three enzymes, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST). In the CNS, H(2)S, generated mainly by CBS in astrocytes and 3MST in neurons, appears to participate in cognition, memory, regulation of the cardiopulmonary functions and neuroprotection. In the peripheral nervous system, evidence suggests that H(2)S may be involved in autonomic control of the cardiopulmonary and gastrointestinal functions as well pain and inflammation.


Neural crest induction by paraxial mesoderm in Xenopus embryos requires FGF signals.
At the border of the neural plate, the induction of the neural crest can be achieved by interactions with the epidermis, or with the underlying mesoderm. Wnt signals are required for the inducing activity of the epidermis in chick and amphibian embryos. Here, we analyze the molecular mechanisms of neural crest induction by the mesoderm in Xenopus embryos. Using a recombination assay, we show that prospective paraxial mesoderm induces a panel of neural crest markers (Slug, FoxD3, Zic5 and Sox9), whereas the future axial mesoderm only induces a subset of these genes. This induction is blocked by a dominant negative (dn) form of FGFR1. However, neither dnFGFR4a nor inhibition of Wnt signaling prevents neural crest induction in this system. Among the FGFs, FGF8 is strongly expressed by the paraxial mesoderm. FGF8 is sufficient to induce the neural crest markers FoxD3, Sox9 and Zic5 transiently in the animal cap assay. In vivo, FGF8 injections also expand the Slug expression domain. This suggests that FGF8 can initiate neural crest formation and cooperates with other DLMZ-derived factors to maintain and complete neural crest induction. In contrast to Wnts, eFGF or bFGF, FGF8 elicits neural crest induction in the absence of mesoderm induction and without a requirement for BMP antagonists. In vivo, it is difficult to dissociate the roles of FGF and WNT factors in mesoderm induction and neural patterning. We show that, in most cases, effects on neural crest formation were parallel to altered mesoderm or neural development. However, neural and neural crest patterning can be dissociated experimentally using different dominant-negative manipulations: while Nfz8 blocks both posterior neural plate formation and neural crest formation, dnFGFR4a blocks neural patterning without blocking neural crest formation. These results suggest that different signal transduction mechanisms may be used in neural crest induction, and anteroposterior neural patterning.


Identification of glutathione conjugates formed from N-hydroxy-2-acetylaminofluorene in the rat.
Rats which had received N-hydroxy-2-acetylaminofluorene (N-OH-AAF) excreted two glutathione conjugates in the bile. Pretreatment with the sulphotransferase inhibitor pentachlorophenol reduced the amounts excreted by 50% suggesting that these conjugates were formed in vivo from the highly reactive N-O-sulphate ester of N-OH-AAF (AAF-N-sulphate). In order to identify these biliary conjugates synthetic GSH conjugates were prepared by the reaction of N-acetoxy-AAF, (a model compound for AAF-N-sulphate), with GSH. Four conjugates were isolated and characterized by ultraviolet, proton magnetic resonance, mass spectroscopy and by the determination of their amino acid composition. These conjugates were identified as 1-, 3-, 4- and 7-(glutathion-S-yl)-N-acetyl-2-aminofluorene, respectively. The two biliary conjugates were identified as 1- and 3-(glutathion-S-yl)-N-acetyl-2-aminofluorene.


Effect of SLCO1B1 polymorphism on induction of CYP3A4 by rifampicin.
Rifampicin (rifampin) is a potent inducer of cytochrome P450 (CYP) 3A4. It was recently identified as a substrate of the polymorphic organic anion transporting polypeptide 1B1 (OATP1B1) expressed on the sinusoidal membrane of human hepatocytes. The present study aimed to investigate the possible association of single nucleotide polymorphisms (SNP) in the SLCO1B1 gene encoding for OATP1B1 with the inducing effect of rifampicin on hepatic CYP3A4. A total of 38 healthy volunteers who had participated in drug interaction studies with rifampicin were genotyped for the g. - 11187G > A and c.521T > C SNPs in SLCO1B1, c.3435C > T SNP in ABCB1 and g.6986A > G SNP in CYP3A5. The plasma concentration of 4beta-hydroxycholesterol, an endogenous marker of CYP3A4 activity, was measured before and after administration of 600 mg rifampicin once daily for 9-11 days. Treatment with rifampicin significantly increased the mean +/- SD plasma concentration of 4beta-hydroxycholesterol from 55.2 +/- 17.9 ng/ml to 120.9 +/- 32.0 ng/ml (P < 0.001). A large intersubject variability existed in the induction of CYP3A4 by rifampicin, but no associations were observed between the variability in induction and any of the polymorphisms studied. These data suggest that SLCO1B1 polymorphism does not affect the extent of induction of hepatic CYP3A4 by rifampicin, probably because other uptake transporters, such as OATP1B3, can compensate for reduced uptake of rifampicin by OATP1B1. However, the present study had sufficient power to detect only a considerably smaller rifampicin-induced increase in 4beta-hydroxycholesterol in carriers of the SLCO1B1 c.521C allele compared to subjects with the reference genotype.


Short communication: interaction of bovine milk protein with chlorpyrifos.
Dairy products are considered as nutrient-dense foods and consumed by many people in western countries, as well as an increasing number of Asian people. Excessive and frequent application of pesticides on vegetables and fruits leads to a potential health hazard to consumers. The organophosphate insecticide chlorpyrifos has been reported to bind with human and bovine serum albumin. Thus, it is necessary to explore the interaction between food protein and chlorpyrifos. In this study, equilibrium dialysis and fluorescence spectra were used to demonstrate binding of milk proteins to chlorpyrifos. The amount of milk protein bound was 0.03±0.01mg/g. Moreover, the milk protein-chlorpyrifos complexes were stable at pH 3.5to 9.5 and ion concentrations from 0.1 to 1.0M. The amount of chlorpyrifos bound to milk proteins decreased to 50% after being in vitro digested by pepsin and trypsin. The results showed that the interaction between food proteins and the pesticide might partially remove the insecticide and reduce the concentration of pesticide absorbed into the blood and, thus, alleviate the corresponding toxicity.


Local anesthetic drugs: penetration from the spinal extradural space into the neuraxis.
Local anesthetics, injected into the spinal extradural space, can be recovered from the spinal cord and brain. Transport from the extradural space into the neuraxis is independent of an active circulation. Distribution is greatest in the periphery of the cord and is most intense near the site of injection. The drugs probably diffuse into the subperineural spaces of the mixed nerves and then pass centripetally along the spinal roots into the cerebrospinal fluid and the cord.


[RF ablation in a patient with recurrent post-infarction ventricular tachycardia requiring multiple cardioverter-defibrillator interventions].
A case of a 51 year old patient with a history of myocardial infarction (MI) and recurrent ventricular tachycardia (VT) is presented. Three months after MI the patient underwent coronary angioplasty and one year later received prophylactic implantable cardioverter-defibrillator (ICD) due to complex ventricular arrhythmias, detected on Holter ECG monitoring, and depressed left ventricular ejection fraction. Later on the patient started to experience palpitations and ICD shocks during physical activity (cycling). Interrogation of the ICD memory showed appropriate shocks due to slow (160 betas/min) VT. The device was reprogrammed and new antitachycardia pacing (ATP) algorithms were enabled, however, it occurred proarrhythmic due to the ATP-induced acceleration of VT rate. Finally, in April 2005 he received 37 appropriate ICD shocks during a few hours. The patient was selected for RF ablation and underwent successful procedure with the use of the electro-anatomical CARTO mapping system.


Environment polluting conventional chemical control compared to an environmentally friendly IPM approach for control of diamondback moth, Plutella xylostella (L.), in China: a review.
The diamondback moth, Plutella xylostella, is recognized as a widely distributed destructive insect pest of Brassica worldwide. The management of this pest is a serious issue, and an estimated annual cost of its management has reached approximately US$4 billion. Despite the fact that chemicals are a serious threat to the environment, lots of chemicals are applied for controlling various insect pests especially P. xylostella. An overreliance on chemical control has not only led to the evolution of resistance to insecticides and to a reduction of natural enemies but also has polluted various components of water, air, and soil ecosystem. In the present scenario, there is a need to implement an environmentally friendly integrated pest management (IPM) approach with new management tactics (microbial control, biological control, cultural control, mating disruption, insecticide rotation strategies, and plant resistance) for an alternative to chemical control. The IPM approach is not only economically beneficial but also reduces the environmental and health risks. The present review synthesizes published information on the insecticide resistance against P. xylostella and emphasizes on adopting an alternative environmentally friendly IPM approach for controlling P. xylostella in China.


Patellar height ratios in children: an interobserver study of three methods.
Several indices for patellar height measurement have been described to relate patellofemoral instability and maltracking. No known study has proved interobserver reliability of these indices when applied to growing knees. This study included comparisons of three of these indices: Caton-Deschamps, Blackburne-Peel, and Koshino. Three observers measured patellar height on 36 lateral radiographs of children's knees. The best interobserver agreement was achieved by the Caton-Deschamps method, a simple, reliable, and reproducible index that is not affected by skeletal maturation.


Keratoconus with good unaided visual acuities: two case reports.
Ophthalmic evaluation of patients with keratoconus (KC) often reveals highly myopic and irregular astigmatic refractive corrections. Irregular corneal astigmatism and central corneal scarring in patients with KC often result in a loss of best-corrected spectacle acuity. Rigid gaspermeable contact lenses generally optimize visual acuities for patients with KC. Two cases are discussed of patients who manifested clinically diagnosed KC but unusually good unaided Snellen visual acuities (20/25+ or better) in both eyes. Good unaided visual acuities are not necessarily inconsistent with the diagnosis of KC.


Dehydroquinate synthase: the role of divalent metal cations and of nicotinamide adenine dinucleotide in catalysis.
The cofactor requirements of dehydroquinate synthase from Escherichia coli have been characterized. The homogeneous enzyme, purified from the overproducing strain RB791 (pJB14), is a monomeric metalloenzyme of Mr = 39,000 that contains 1 mol of tightly bound Co(II) according to atomic absorption analysis. The holoenzyme rapidly loses activity upon incubation with EDTA, giving rise to a stable but catalytically inactive apoenzyme. Activity is fully restored by reconstitution with Co(II) and partially restored with other divalent cations. Reconstitution of the apoenzyme with Zn(II) (which is probably the functioning metal in vivo) restores activity to 53% of the level observed with the Co(II)-holoenzyme. The presence of the substrate 3-deoxy-D-arabino-heptulosonate 7-phosphate (1) blocks the inactivation by EDTA. Dehydroquinate synthase also binds 1 mol of NAD+, the presence of which is essential for catalytic activity. The rate constant for the dissociation of NAD+ from the Co(II)-holoenzyme was found to be 0.024 min-1. Under turnover conditions with saturating levels of substrate, the dissociation rate of NAD+ increases by a factor of 40, to 1 min-1. Under these conditions (pH 7.5, 20 degrees C), the Km for NAD+ was determined to be 80 nM.


[Kudo non-constrained elbow prosthesis for inflammatory and hemophilic joint disease: analysis in 30 cases].
We analyzed retrospectively 30 Kudo non-constrained elbow prostheses to determine: 1) functional outcome and mobility, 2) frequency of loosening and any complications. From 1992 to 1998, 30 Kudo total elbow arthroplasties were performed in 29 patients, mean age 55 years. Mean follow-up was 36 months. These patients had severe joint disease: rheumatoid arthritis for 24, psoriatic arthritis for 2, and hemophilic arthritis for 3. The 29 patients experienced severe pain before surgery. At review, 21 elbows were pain free and the 9 others had only occasional pain. Among these 9 elbows, 3 exhibited a rupture of the humeral implant; one had already been revised but remained painful. One patient had a stiff painful elbow after reflex dystrophy and five others had pain but no other complication. Twenty-six patients were satisfied or very satisfied. Three patients were unsatisfied because of the humeral implant fracture. Mean mobility at last follow-up was: 128 degrees flexion, -35 degrees extension, 72 degrees pronation, and 74 degrees supination. Mean gain in flexion-extension was 15 degrees and mean gain in pronosupination was 3 degrees. Pronosupination was greater than 100 degrees except for two patients. There was one immediate post-operative dislocation with failure of prolonged orthopedic treatment after reduction; this patient underwent revision reconstruction with repair of the ulnar collateral ligaments (plasty of the medial collateral ligament with a synthetic ligament). Painful movement of the radial stump was observed with one Kudo prosthesis and required resection to achieve cure. In all, there were 3 fractures of the Kudo I prosthesis at the junction of the trochlea and the humeral stem. Among these patients, one underwent revision due to persistent pain, and two others with currently acceptable symptoms are awaiting revision. At last follow-up, we had: 1 ulnar loosening associated with cortical thinning facing the end of the ulnar implant that had migrated and showed a circular lucent line measuring > 1 mm and progressing; 9 unique ulnar lucent lines measuring<1 mm without progression at the proximal part of the implant (6 at the bone-cement interface and 3 at the bone-implant interface); 3 humeral radiolucent lines (<1 mm without progression) on the distal part of the Kudo II humeral stems corresponding to a zone without surfacing. We also observed 13 cases of incomplete ossification between the humerus and ulna and among these 13, 7 elbows had amplitudes of less than 100 degrees. Elbow arthroplasty can restore a painless joint and maintain or improve elbow motion. The procedure is indicated when the joint disease impair daily life activities. Final mobility basically depends on the preoperative mobility. The bone stock remains the greatest problem with these resurfaced prostheses. The GUEPAR elbow prosthesis would appear to be more adapted due to the reconstruction of the trochlea. Resection of the radial head is a source of instability for elbow prostheses and should lead to the design of three-compartment prostheses.


Innervation of the smooth muscle of the lower urinary tract.
The lower urinary tract in mammals consists of the bladder, a storage organ for urine, and the urethra through which urine is expelled to the outside. In the male the urethra extends outside the body as the penis. The lower urinary tract is innervated by pelvic (parasympathetic) nerves and hypogastric nerves which combine on each side at the pelvic plexus. Fibres pass to the bladder, urethra, genital organs, rectum and blood vessels. In addition to the pelvic and hypogastric nerves there is sacral outflow to skeletal muscle, such as the external sphincters of the urethra and anus, in the pudendal nerve and the sympathetic chain extends caudally with branches lying in the sacral outflow that supply the penis and other organs though not the bladder. Bladder evacuation and penile erection are produced by activity of the pelvic nerves whereas sympathetic activity usually dominates during urine storage and penile flaccidity, though it may not be essential for either.


Differential patterns of morphological and molecular hybridization between Fraxinus excelsior L. and Fraxinus angustifolia Vahl (Oleaceae) in eastern and western France.
We examined large-scale patterns of morphology, genetic structure and ecological correlates of Fraxinus excelsior and the closely related species Fraxinus angustifolia in France, in order to determine the degree of hybridization between them. We sampled 24 populations in two putative hybrid zones (Loire and Saône), and five control populations of each species. We measured foliar characteristics of adult trees and used five nuclear microsatellites as molecular markers. Canonical discriminant analysis indicated that the two species differ in morphology, but that intermediate types are common in the Loire region but less frequent in the Saône region. Bayesian population assignment identified one F. angustifolia and two F. excelsior gene pools. Most Loire individuals clustered genetically with the F. angustifolia gene pool. In contrast, the Saône region presented individuals belonging mostly to F. excelsior pools, although the F. angustifolia type was frequent in certain populations. The lowest F(ST) values were found between the Loire and F. angustifolia controls that also exhibited no significant isolation by distance. The proportion of the F. angustifolia gene pool in each locality was negatively correlated with winter temperatures, suggesting that a cold climate may be limiting. Hybridization is probably favoured by the intermediate climatic conditions in the Loire region that allow both species to occur, but is somewhat hampered by the harsher winters in the Saône area where morphological introgression has apparently not yet occurred.


Interaction of exercise training and clenbuterol on GLUT-4 protein in muscle of obese Zucker rats.
Chronic administration of clenbuterol, a beta 2-adrenergic agonist, attenuates the exercise training-induced improvement in muscle insulin resistance of the obese Zucker rat. The present study was conducted to determine whether clenbuterol also attenuates the increase in muscle GLUT-4 protein that occurs with exercise training and whether the action of clenbuterol is related to its ability to downregulate the beta-adrenergic receptors. Female obese Zucker rats were randomly assigned to one of the following four groups: control (CON, n = 7), clenbuterol (CL, n = 8), exercise training (TR, n = 8), and clenbuterol with exercise training (CL+TR, n = 8). Rats assigned to the training groups were run on a rodent motor-driven treadmill for 6-7 wk. Rats receiving clenbuterol were intubated with 0.8 mg/kg body weight 30 min before running each day. Red quadriceps (RQ) and white quadriceps (WQ) GLUT-4 protein concentrations of TR rats were significantly greater than those of CON and CL+TR rats. The RQ GLUT-4 protein concentration of the CL+TR rats was significantly greater than that of CON rats, but this difference did not occur in the WQ. GLUT-4 protein concentrations were not different between the CON and CL rats. The patterns of RQ and WQ GLUT-4 mRNA were similar to those of their respective GLUT-4 proteins. Rats receiving daily injections of propranolol (30 mg/kg body wt), a beta-adrenergic receptor antagonist, demonstrated no increase in GLUT-4 protein in RQ or WQ after 6 wk of exercise training. These results indicate that 1) clenbuterol can attenuate the increase in muscle GLUT-4 protein associated with exercise training and 2) this effect is likely mediated by a downregulation of the beta-adrenergic receptors.


Assessment of physically-based and data-driven models to predict microbial water quality in open channels.
In the present study, a physically-based hydraulic modeling tool and a data-driven approach using artificial neural networks (ANNs) were evaluated for their ability to simulate the fate and transport of microorganisms in a water system. To produce reliable data, a pipe network was constructed and a series of experiments using a fecal coliform indicator (Escherichia coli 15597) was conducted. For the physically-based model, morphological (pipe size, link length, slope, etc.) and hydraulic (flow rate) conditions were used as input variables, and for ANNs, water quality parameters (conductivity, pH, and turbidity) were used. Both approaches accurately described the fate and transport of microorganisms (physically-based model: correlation coefficient (R) in the range of 0.914-0.977 and ANNs: R in the range of 0.949 - 0.980), with the exception of one case at a low flow rate (q = 31.56 cm3/sec). This study also indicated that these approaches could be complementarily utilized to assess the vulnerability of water facilities and to establish emergency plans based on hypothetical scenarios.


[Basic and clinical studies on cefminox in the field of obstetrics and gynecology].
Human pharmacokinetics and clinical studies of cefminox (CMNX, MT-141) were carried out and the following results were obtained. The concentrations of CMNX transferred to the uterus and its appendages after CMNX 1 g intravenous injection were maintained above 12.5 micrograms/g during first 3 hours or more. The concentrations of CMNX transferred to the pelvic dead space exudate were above 12.5 micrograms/ml during 6 hours or more. Those concentrations were sufficiently effective against the major pathogens (Gram-negative and anaerobic bacteria) demonstrated in the field of obstetrics and gynecology. We administered CMNX to 4 cases with postoperative infections at a dose of 2 g per day (twice a day) for a period of 4-6 days. The clinical effect was excellent in 3, good in 1 case. No side effect was observed.


[Acute bronchiolitis due to Mycoplasma pneumoniae and successfully treated with steroids].
A high fever, coughing, stridor, and dyspnea developed in a 52-year-old woman on October 19, 1995. She went to a local clinic and was treated with oral penicillin and intravenous cefpirome. The symptoms worsened, and she was admitted to our hospital on October 26. Coarse crackles and wheezing were heard in both lung fields. The white blood cell count was 9000/mm3 and arterial blood gas analysis revealed a PaO2 of 49.8 Torr on room air. A chest roentgenogram obtained on admission showed a few small bibasilar nodular infiltrates, and a chest CT scan showed thickened bronchial walls along with small nodules having a centrilobular distribution. Of the cells in bronchoalveolar lavage fluid, 88% were neutrophils, but tests for bacteria and mycobacteria were negative. The cold-agglutinin titer was 1:512. The Mycoplasma pneumoniae antibody titer (IIIA) was 1:640 and viral serology tests were negative. Acute bronchiolitis due to M. pneumoniae was diagnosed and treatment with intravenous minocycline was started. The symptoms (coughing, fever, and stridor) resolved and the small nodules on chest CT scan disappeared, but hypoxemia remained. At the same time, an obstructive ventilatory defect (FEV1% 62.8%) and abnormal ventilation/perfusion lung scans were noted. Development into bronchiolitis obliterans was suspected, so administration of methyl prednisolone (1 g/day for 3 days) and prednisolone was started. The response to steroids was good. Pulmonary function improved and the arterial PaO2 at the time of discharge was 86 Torr (room air). Use of steroid therapy in the early phase of bronchiolitis obliterans seemed to be effective.


Are There Prognostic Factors for One-Year Outcome After Total Knee Arthroplasty? A Systematic Review.
Preoperative factors predicting outcome for pain, physical function and quality of life after total knee arthroplasty (TKA) have not been clearly identified. Embase and MEDLINE were searched for relevant studies. A study was considered for inclusion if the study aimed to identify preoperative prognostic factors for pain, physical function, and/or quality of life after a follow-up period of at least 1 year; included at least 200 adults suffering from osteoarthritis and undergoing TKA; and analyzed data using multivariable modeling. The quality of the evidence per prognostic factor was determined using the Grading of Recommendations, Assessment, Development and Evaluation framework for prognosis studies. A total of 18 studies were included. There is very low-quality evidence that preoperative more pain, presence of social support, absence of anxiety, and presence of more radiographic damage are prognostic factors for lower pain levels after TKA. There is very low-quality evidence that low preoperative physical function, less comorbidity, absence of anxiety, presence of social support, higher income, normal body mass index, and more radiographic damage are prognostic factors for better physical function. There is very low-quality evidence that female sex and less comorbidity are prognostic factors for better quality of life. Only very low-quality evidence was found for a number of prognostic factors of long-term outcome after TKA. More studies that seek to generate understanding of the underlying process for the prognosis of outcome in TKA are needed to understand and test prognostic pathways, and it might be more valuable to look at recovery curves rather than at recovery points. Systematic review registration number: CRD42015026814.


Myasthenia gravis: signs, symptoms, diagnosis, immunology, and current therapy.
Myasthenia gravis is a neuromuscular disease that presents clinically as fluctuating weakness of one or more skeletal muscle groups. Weakness becomes more severe with exercise and improves with rest. The disease is caused by an autoimmune reaction at or near the post-synaptic nicotinic acetylcholine receptor. The results of this immune reaction are the lytic destruction of the post-synaptic membrane and a reduction in the number of acetylcholine receptors. Myasthenia gravis can be diagnosed by repetitive exercise of the involved muscles, administration of edrophonium (Tensilon), electrophysiologic testing, or demonstration of anti-acetylcholine receptor antibodies. When the myasthenic weakness is mild or limited to the extraocular muscles, it may be treated with acetylcholinesterase inhibitors. When the weakness is more severe and/or more generalized, immunotherapy is most often indicated. Prednisone or prednisone plus thymectomy is the most frequently used form of immunotherapy. Azathioprine, 6-mercaptopurine, plasmapheresis, or gamma globulin injections are other immunotherapeutic options that may be useful in selected patients. A large number of drugs may precipitate or exacerbate myasthenic weakness.


Cohesion induced by a rotating magnetic field in a granular material.
We report experiments on a magnetic cohesive granular material made of steel spheres in the millimeter range. A magnetic field magnetizes the spheres, so that an interaction force between grains appears. A rotating magnetic field is applied parallel to plane of the quasi-two-dimensional cell containing the spheres so that only the time averaged force between two particles will be considered. Both maximum angle of stability and angles of repose are measured. The maximum angle of stability is found to depend linearly on the interaction force. Another noticeable feature is the lack of dependence of the maximum angle of stability on the initial height of the heap. We show that the angle of repose is less sensitive to the magnetic interaction force than the maximum of stability. At last, we discuss the importance of using a rotating field rather than a constant one. In particular, we report some measurements of both the maximum angle of stability and the angle of repose in constant field, which show a strong dependence of the angles of avalanche on the direction of the field.


Immunologic heterogeneity among potential transplant recipients. Prospects for predicting immune responses to allografts with in vitro tests.
The ability to accurately predict the response of a specific patient to a specific organ allograft has long been a goal of organ transplantation. The role of histocompatibility antigens in determining the acceptance or rejection of an allograft-recipient combination has been thoroughly investigated, but is being reevaluated as improved immunosuppressive agents become available. Early efforts at immunologic monitoring are reviewed in addition to more recent efforts that focus on the cellular and molecular mediators of immunity. The authors' own experience with lymphokine measurements in clinical transplantation is also reviewed, with emphasis on the role of interleukin-2 (IL-2) and its soluble receptor (IL-2R) in various transplant-associated conditions. The authors conclude that information useful in the management of transplant patients may be derived from serial measurements of IL-2 and IL-2R, but that infections, especially CMV, may not be ruled out with certainty by these measurements alone. The available data suggest that study of additional lymphokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) may be useful in discriminating rejection from infections in transplant patients.


Hemodialysis for methanol intoxication.
A patient with toxic levels of methanol was hemodialyzed while receiving an ethanol infusion. It was demonstrated that during the dialysis significant quantities of both ethanol (17.70 gms) and methanol (26.69 gms) were extracted. Also, it was shown that the ethanol did not competetively inhibit the extraction of the methanol. Since ethanol is removed in significant quantities during dialysis, one should increase its infusion rate during hemodialysis and decrease the rate when the patient is not being dialyzed. This would achieve adequate and constant blood levels of ethanol and would satisfactorily inhibit the metabolism of methanol by the liver.


Oncogenic Circular RNAs Arise from Chromosomal Translocations.
Fusion-circular RNAs (f-circRNA) can result from tumor-associated chromosomal translocations.


The glutamate-isolated mass receptor potential of the frog's retina. I. General properties and intensity dependence.
The glutamate-isolated mass receptor potential of the superfused frog's retina was investigated in order to find a method for discrimination of both rod and cone contribution to the sum response. After mesopic white light stimuli the potential showed a biphasic decay with a rapid and a slow part, respectively. Regarding threshold, saturation, light adaptation, and time course, the rapid decay is shown to correspond to the cone response. The remaining part of mass receptor potential, on the other hand, resembled the rod response in all these properties. This analysis provides the basis for studying the cation dependence of rod and cone receptor potentials with the stable mass receptor potentials. Moreover, the time course of the rod's light response is discussed to draw some conclusions regarding the internal transmission in rod photoreceptors.


Qualitative and quantitative mass spectrometry of some biologically important trace metals as their tetraphenylporphyrin chelates.
The use of the mass spectrometric integrated ion current technique for the quantitative analysis of some trace metals at their tetraphenylporphyrin chelates is described. The linearity of the calibration curves and the sensitivity of the technique are improved by employing deuterated tetraphenylporphyrin chelates as loading agents. Femtomole quantities of the chelates may be detected. The use of deuterated tetraphynylporphyrin chelates as internal standards overcomes the problems of losses occurring during chromatographic separation and by thermal decomposition in the mass spectrometer.


The value of primary, secondary, and plantation forests for a neotropical herpetofauna.
Plantation forests and second-growth forests are becoming dominant components of many tropical forest landscapes. Yet there is little information available concerning the consequences of different forestry options for biodiversity conservation in the tropics. We sampled the leaf-litter herpetofauna of primary, secondary, and Eucalyptus plantation forests in the Jari River area of northeastern Brazilian Amazonia. We used four complementary sampling techniques, combined samples from 2 consecutive years, and collected 1739 leaf-litter amphibians (23 species) and 1937 lizards (30 species). We analyzed the data for differences among forest types regarding patterns of alpha and beta diversity, species-abundance distributions, and community structure. Primary rainforest harbored significantly more species, but supported a similar abundance of amphibians and lizards compared with adjacent areas of second-growth forest or plantations. Plantation forests were dominated by wide-ranging habitat generalists. Secondary forest faunas contained a number of species characteristic of primary forest habitat. Amphibian communities in secondary forests and Eucalyptus plantations formed a nested subset of primary forest species, whereas the species composition of the lizard community in plantations was distinct, and was dominated by open-area species. Although plantation forests are relatively impoverished, naturally regenerating forests can help mitigate some negative effects of deforestation for herpetofauna. Nevertheless, secondary forest does not provide a substitute for primary forest, and in the absence of further evidence from older successional stands, we caution against the optimistic claim that natural forest regeneration in abandoned lands will provide refuge for the many species that are currently threatened by deforestation.


Evidence from normal and degenerating photoreceptors that two outer segment integral membrane proteins have separate transport pathways.
Detachment of the neural retina from the retinal pigment epithelium induces photoreceptor degeneration. We studied the effects of this degeneration on the localization of two photoreceptor outer segment-specific integral membrane proteins, opsin and peripherin/rds, in rod photoreceptors. Results from laser scanning confocal microscopic and electron microscopic immunolocalization demonstrate that these two proteins, normally targeted to the newly-forming discs of the outer segments, accumulate in different sub-cellular compartments during photoreceptor degeneration: opsin immunolabeling increases throughout the photoreceptor cell's plasma membrane, while peripherin/rds immunolabeling occurs within cytoplasmic vesicles. The simplest hypothesis to explain our results is that these proteins are transported in different post-Golgi transport vesicles and separately inserted into the plasma membrane. More complex mechanisms involve having the two co-transported and then opsin finds its way into the plasma membrane but peripherin/rds does not, remaining behind in vesicles. Alternatively, both insert into the plasma membrane but peripherin/rds is recycled into cytoplasmic vesicles. We believe the data most strongly supports the first possibility. Although the transport pathways for these proteins have not been fully characterized, the presence of peripherin/rds-positive vesicles adjacent to the striated rootlet suggests a transport role for this cytoskeletal element. The accumulation of these proteins in photoreceptors with degenerated outer segments may also indicate that their rate of synthesis has exceeded the combined rates of their incorporation into newly forming outer segment disc membranes and their degradation. The accumulation may also provide a mechanism for rapid recovery of the outer segment following retinal reattachment and return of the photoreceptor cell to an environment favorable to outer segment regeneration.


Identification of biogenic organotellurides in Escherichia coli K-12 headspace gases using solid-phase microextraction and gas chromatography.
Escherichia coli JM109 cells, expressing the genes encoded in a 3.8-kb chromosomal DNA fragment from Geobacillus stearothermophilus V, produced volatile organotellurium compounds which were released into the headspace gas above liquid cultures when amended with tellurite anions in micromolar amounts. Headspace sampling was achieved using gas-syringe extraction or solid-phase microextraction using carboxen-polydimethysiloxane fibers. In addition to dimethyl telluride and dimethyl ditelluride, two new organometalloidal compounds were detected using gas chromatograph with mass spectrometric or fluorine-induced chemiluminescence detection. These compounds are methanetellurol and dimethyl tellurenyl sulfide. The significance of these findings with regard to the current knowledge about bacterial tellurite resistance is discussed.


Genistein affects HER2 protein concentration, activation, and promoter regulation in BT-474 human breast cancer cells.
The HER2 proto-oncogene, a member of the epidermal growth factor receptor family, is overexpressed in 20-30% of breast cancers. Genistein, the main soy isoflavone, interacts with estrogen receptors (ER) and it is also a potent tyrosine kinase inhibitor. Previously, our laboratory found that genistein delayed mammary tumor onset in transgenic mice that overexpress HER2 gene. Our goal was to define the mechanism through which genistein affects mammary tumorigenesis in HER2 overexpressing mice. We hypothesized that genistein inhibits HER2 activation and expression through ER-dependent and ER-independent mechanisms. Genistein inhibited total HER2 protein expression and tyrosine phosphorylation in BT-474, an ERalpha (-) and ERbeta (+) human breast cancer cell line, however, E2 had no effect. Taken together, these data suggest that genistein has an ER-independent inhibitory effect, presumably, through tyrosine kinase inhibition activity. Genistein at 1.0 microM mimicked E2 and down-regulated HER2 protein phosphorylation when BT-474 was co-transfected with ERalpha, but not ERbeta. Although E2 and overexpression of HER2 can promote mammary tumorigenesis, an inverse relationship between ER expression and HER2 overexpression has been found in human breast cancer. We cloned a 500-bp promoter region upstream of the HER2 transcription initiation site. Co-transfection with ERalpha, but not with ERbeta, down-regulated HER2 promoter reporter in BT-474. At concentrations > or =1 microM, genistein inhibited HER2 promoter reporter in the absence of ERalpha. In conclusion, genistein at > or =1 microM inhibited HER2 protein expression, phosphorylation, and promoter activity through an ER-independent mechanism. In the presence of ERalpha, genistein mimicked E2 and inhibited HER2 protein phosphorylation. These data support genistein's chemo-prevention and potential chemo-therapeutic roles in breast cancer.


Role of attachment in response to pet loss.
This study examined the impact of attachment on grief severity following the death of a pet. Seventy-one participants who had lost a dog or cat within the past year completed a set of measures that included an attachment measure assessing individual differences in attachment anxiety and avoidance, strength of the past attachment to the pet, the continuing bond with the deceased pet, social support, and complicated grief symptoms. Attachment anxiety and strength of the past attachment to the pet were each uniquely predictive of more severe grief. Furthermore, the continuing bond to the deceased pet partially mediated the impact of strength of the past attachment to the pet on grief severity. No significant mediators of the effect of attachment anxiety on grief were found, however. The results highlight the importance of distinguishing strength of attachment from attachment security in examining the effect of attachment on response to pet loss.


Personality dynamics: insights from the personality social cognitive literature.
Psychodynamic and social cognitive approaches to personality assessment converge now more so than at any time in the history of experimental psychology. This contribution seeks to make this point. First, the trait of neuroticism predisposes one to multiple adverse outcomes, a point not sufficiently captured by the current version of the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994). Second, though, self-reported levels of neuroticism are insufficient in understanding problematic outcomes for multiple reasons. Third, there are ways of experimentally modeling the many processes of interest to psychodynamic theorists such as unconscious affective biases, implicit representations of self and other, and underlying deficits in self- and emotion regulation. Implicit approaches to assessment also provide clues to interventions targeting the processes of interest, a point that will be made as well.


Effects of child care center ventilation strategies on volatile organic compounds of indoor and outdoor origins.
Preschool children can be at risk from harmful volatile organic compounds (VOCs) exposures in child care centers (CCCs). However, the effectiveness of ventilation for mitigating indoor VOCs exposures from myriad sources in CCCs is unclear. We investigated relationships between indoor exposures and risks of VOCs from indoor and outdoor sources under differentventilation strategies in 104 tropical CCCs. Factor analyses identified five dominant source groups of which four were associated with indoor sources, and one was associated with both indoor and outdoor sources. Indoor VOCs exposures and risks associated with indoor sources were lower in naturally (NV) and hybrid ventilated (HB) CCCs compared to air-conditioned CCCs (ACMV and AC). This is attributed to enhanced dilution via higher ventilation in NV and HB CCCs compared to ACMV and AC CCCs. Conversely, there were no discernible differences in VOCs exposures and risk associated with both indoorand outdoor sources across differentventilation strategies. The observations made in this study have implications of ventilation strategies used in other settings. To mitigate VOCs exposures and risk, it is important to identify their major indoor and outdoor sources first.


Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production.
The Akt/protein kinase B (PKB) serine/threonine kinase is well known as an important mediator of many cell survival signaling pathways. Here, we demonstrate for the first time a major role of Akt/PKB in the cell invasion properties of the highly metastatic cell line HT1080. Using confocal microscopic analyses of live samples, we found Akt/PKB to be localized in the leading edge membrane area of migrating HT1080 cells. This localization was dependent on phosphoinositide 3-kinase and required the lipid binding ability of the phosphoinositide binding pleckstrin homology domain of Akt/PKB. We examined the possible function of Akt/PKB in HT1080 invasion. Surprisingly, Akt/PKB potently promoted HT1080 invasion, by increasing cell motility and matrix metalloproteinase-9 (MMP-9) production, in a manner highly dependent on its kinase activity and membrane-translocating ability. The increase in MMP-9 production was mediated by activation of nuclear factor-kappaB transcriptional activity by Akt/PKB. However, Akt/PKB did not affect the cell-cell or cell-matrix adhesion properties of HT1080. Our findings thus establish Akt/PKB as a major factor in the invasive abilities of cancer cells.


The aromatic peroxygenase from Marasmius rutola--a new enzyme for biosensor applications.
The aromatic peroxygenase (APO; EC 1.11.2.1) from the agraric basidomycete Marasmius rotula (MroAPO) immobilized at the chitosan-capped gold-nanoparticle-modified glassy carbon electrode displayed a pair of redox peaks with a midpoint potential of -278.5 mV vs. AgCl/AgCl (1 M KCl) for the Fe(2+)/Fe(3+) redox couple of the heme-thiolate-containing protein. MroAPO oxidizes aromatic substrates such as aniline, p-aminophenol, hydroquinone, resorcinol, catechol, and paracetamol by means of hydrogen peroxide. The substrate spectrum overlaps with those of cytochrome P450s and plant peroxidases which are relevant in environmental analysis and drug monitoring. In M. rotula peroxygenase-based enzyme electrodes, the signal is generated by the reduction of electrode-active reaction products (e.g., p-benzoquinone and p-quinoneimine) with electro-enzymatic recycling of the analyte. In these enzyme electrodes, the signal reflects the conversion of all substrates thus representing an overall parameter in complex media. The performance of these sensors and their further development are discussed.


[Research on association between atherosclerotic brain infarction and human leukocyte antigen DR gene].
To evaluate the relationship between atherosclerotic brain infarction (ABI) and human leukocyte antigen DR (HLA-DR) gene at molecular level. By using polymerase chain reaction sequence specific probe (PCR-SSP), gene special position of the HLA-II DR alleles were determined in 31 patients and 30 healthy individuals as controls, all of them were inhabitants of Northeastern China. The HLA-DR B1*0301 gene frequency in the group of ABI was obviously higher than that of control group (RR=5.6842, P<0.05). The HLA-DR B1*0301 gene may be the susceptible gene of ABI in Northeastern China, or it may associate with other genes to produce the disease.


Comparing Norwegian nurses' and physicians' perceptions of the needs of significant others in intensive care units.
To illuminate and compare the perceptions of registered nurses (n = 243) and physicians (n = 29) in medical and surgical ICUs for adults on the needs of significant others. Previous studies have established the necessity for healthcare professionals in Intensive Care Units (ICUs) to identify and meet the needs of critically ill adult patients' significant others. A survey was conducted and data from the Critical Care Family Needs Inventory were analysed using descriptive and inferential statistics. The findings revealed four factors: 'attentiveness and assurance', 'taking care of themselves', 'involvement', and 'information and predictability'. Nurses scored higher than physicians on 'attentiveness and assurance'. Nurses with experience of being a patient or a significant other in an ICU placed a higher value on 'involvement' compared with nurses without such experience, while physicians with such experience scored higher on 'information and predictability' compared with those without such experience. Older physicians and those with extensive professional and ICU experience had a low score on 'involvement', but scored higher on 'information and predictability' compared with physicians with less experience. Nurses with extensive ICU and professional experience also scored higher on 'information and predictability' than nurses with less experience. Women placed a higher value on each of the four factors than men. The study revealed variations in ICU professionals' perceptions of significant others' needs. There is a need for nurses and physicians to acknowledge that varying perceptions on significant others needs could lead to different ways of conducting themselves in encounters with significant others in ICUs. There is also a risk that the patients' significant others could be forced to adapt themselves to professionals' different and perhaps contradictory perceptions of their needs in ICUs.


Structure of arterivirus nsp4. The smallest chymotrypsin-like proteinase with an alpha/beta C-terminal extension and alternate conformations of the oxyanion hole.
Arteriviruses are enveloped, positive-stranded RNA viruses and include pathogens of major economic concern to the swine- and horse-breeding industries. The arterivirus replicase gene encodes two large precursor polyproteins that are processed by the viral main proteinase nonstructural protein 4 (nsp4). The three-dimensional structure of the 21-kDa nsp4 from the arterivirus prototype equine arteritis virus has been determined to 2.0 A resolution. Nsp4 adopts the smallest known chymotrypsin-like fold with a canonical catalytic triad of Ser-120, His-39, and Asp-65, as well as a novel alpha/beta C-terminal extension domain that may play a role in mediating protein-protein interactions. In different copies of nsp4 in the asymmetric unit, the oxyanion hole adopts either a collapsed inactive conformation or the standard active conformation, which may be a novel way of regulating proteolytic activity.


Radioenzymatic assay for histamine: development and validation.
Radioenzymatic assays are sensitive analytic tools that use an enzyme to quantify a substrate for that enzyme. Purified histamine N-methyltransferase has been used as the basis for an assay for histamine. The sensitivity of the procedure is less than 10 fmol. The specificity of the assay is increased when the transferase reaction is carried out at 0-3 degrees C. Data documenting the precision of the assay, the stability of histamine in human plasma, and the gastric secretory rate of histamine are presented along with a chronologic description of the development of the technique.


Compounded progesterone: why is it acceptable to Australian women?
To determine factors influencing compounded progesterone products' acceptability amongst Australian women who use them. A cross-sectional survey of 366 women from all states of Australia who had been dispensed a compounded progesterone product, using the 'Perspectives on Progesterone' questionnaire. Descriptive statistics and a logistic regression model of acceptability. Acceptability was measured by respondents' willingness to recommend progesterone therapy to other women with a similar condition to their own and whether they had talked about their experience to other women. Australian women who use compounded progesterone tend to be highly educated. They were treating symptoms associated with menopause transition or hormone deficiency. The most common dosage form being used was transdermal cream. More than half the respondents reported improvement for mood swings or irritability (73%), foggy thinking (58%), hot flushes (56%), sleeping problems (55%), and anxiety (54%). Side effects were minimal with the weight gain being the most frequently reported (10%). There was no difference in symptom improvement between those who use progesterone alone or in combination with other hormones. The compounded progesterone acceptability model contains symptom improvement (very large effect size) perception that progesterone is natural and safe (large effect size), number of unexpected benefits (medium effect size) and treatment tailored to suit them (medium effect size). Concerns about other treatments or other treatments being ineffective did not contribute to acceptability. Acceptance of compounded progesterone therapy depends on symptom improvement, perception of safety and naturalness and tailored therapy.


The KIDSCREEN-52 quality of life measure for children and adolescents: psychometric results from a cross-cultural survey in 13 European countries.
This study assesses the reliability and validity of the European KIDSCREEN-52 generic health-related quality of life (HRQoL) questionnaire for children and adolescents. The KIDSCREEN-52, which measures HRQoL in 10 dimensions, was administered to a representative sample of 22,827 children and adolescents (8 to 18 years) in 13 European countries. Psychometric properties were assessed using the Classical Test Theory approach, Rasch analysis, and structural equation modeling (SEM). A priori expected associations between KIDSCREEN scales and sociodemographic and health-related factors were examined. Test-retest reliability was assessed in 10 countries. For the overall sample, Cronbach's alpha values ranged from 0.77 to 0.89. Scaling success (Multitrait Analysis Program) was >97.8% for all dimensions and Rasch analysis item fit (INFITmsq) ranged from 0.80 to 1.27. The intraclass correlation coefficients ranged from 0.56 to 0.77. No sizeable differential item functioning (DIF) was found by age, sex or health status. Four items showed DIF across countries. The specified SEM fitted the data well (root mean square error of approximation: 0.06, comparative fit index: 0.98). Correlation coefficients between Pediatric Quality of Life Inventory, Child Health and Illness Profile-Adolescent Edition, and Youth Quality of Life Instrument scales and KIDSCREEN dimensions assessing similar constructs were moderate for those (r = 0.44 to 0.61). Statistically significant differences between children with and without physical and mental health problems (Children with Special Health Care Needs screener: d = 0.17 to 0.42, Strengths and Difficulties Questionnaire: d = 0.32 to 0.72) were found in all dimensions. All dimensions showed a gradient according to socioeconomic status. The KIDSCREEN-52 questionnaire has acceptable levels of reliability and validity. Further work is needed to assess longitudinal validity and sensitivity to change.


[Categorization of clinical findings; reduction of data without loss of information].
Depending on the individual skill of doctors the results of clinical investigations and laboratory findings are weighted differently according to their reliability today. Dealing with medical data the statistical way they have to be handled differently as well depending on the degree of reproducability and thus reliability. The problem of safety and quality of data in medicine is known to every experienced doctor as long as he himself "processes" them, nevertheless data tend to be treated uncritically when "automatically" processed by a computer. A way out of this pitfall is given by standardization of data using check-lists without transfer to any kind of coding-system or thesauri because none of those systems exists today that is capable of regaining the input-informations as they were from the codes.


In Vitro Generation of Heart Field-specific Cardiac Progenitor Cells.
Pluripotent stem cells offer great potential for understanding heart development and disease and for regenerative medicine. While recent advances in developmental cardiology have led to generating cardiac cells from pluripotent stem cells, it is unclear if the two cardiac fields - the first and second heart fields (FHF and SHF) - are induced in pluripotent stem cells systems. To address this, we generated a protocol for in vitro specification and isolation of heart field-specific cardiac progenitor cells. We used embryonic stem cells lines carrying Hcn4-GFP and Tbx1-Cre; Rosa-RFP reporters of the FHF and the SHF, respectively, and live cell immunostaining of the cell membrane protein Cxcr4, a SHF marker. With this approach, we generated progenitor cells which recapitulate the functional properties and transcriptome of their in vivo counterparts. Our protocol can be utilized to study early specification and segregation of the two heart fields and to generate chamber-specific cardiac cells for heart disease modelling. Since this is an in vitro organoid system, it may not provide precise anatomical information. However, this system overcomes the poor accessibility of gastrulation-stage embryos and can be upscaled for high-throughput screens.


[Purification and study of equine infectious anemia virus antigens, produced in vivo or in cultured cells].
The G and C antigens of equine infectious anemia virus have been produced in vivo and in infected cell culture, then they have been purified. Their physico-chemical properties have been determined, particularly their molecular weight, their sedimentation coefficient, their density and the iso electric point.


Tachykinins with unusual structural features from a urodele, the amphiuma, an elasmobranch, the hammerhead shark, and an agnathan, the river lamprey.
Tachykinins were purified from extracts of gastrointestinal tissues of the urodele, Amphiuma tridactylum (three-toed amphiuma), and the elasmobranch Sphyrna lewini (hammerhead shark), and from the brain of the agnathan Lampetra fluviatilis (river lamprey). The amphiuma substance P (SP) (DNPSVGQFYGLM-NH2) contains 12 amino residues compared with 11 for mammalian SP and lacks the Arg/Lys-Pro-Xaa-Pro motif that is characteristic of NK1 receptor-selective agonists. Lampetra SP (RKPHPKEFVGLM-NH2) is identical to SP from the sea lamprey and the shark SP-related peptide (AKFDKFYGLM-NH2) is identical to dogfish scyliorhinin I. Amphiuma neurokinin A (NKA) (HKDAFIGLM-NH2) and lamprey NKA (HFDEFVGLM-NH2) contain 9 amino acid residues compared with 10 for mammalian NKA. The shark NKA-related peptide (ASGPTQAGIV10GRKRQKGEMF20VGLM-NH2) shows limited structural similarity to mammalian neuropeptide gamma and the teleost tachykinin, carassin but contains 24 rather than 21 amino acid residues. The data show that the primary structures of the tachykinins have been very poorly conserved during vertebrate evolution and that pressure has acted only to maintain the functionally important sequence -Phe-Xaa-Gly Leu-Met-NH2 at the COOH-termini of the peptides.


Linear intensity normalization of DaTSCAN images using Mean Square Error and a model-based clustering approach.
The analysis of 3D SPECT brain images requires several pre-processing steps such as intensity normalization and brain feature extraction. In this sense, a new method for intensity normalization of 123I-ioflupane-SPECT (DaTSCAN) brain images based on minimization of the Mean Square Error (MSE) between the Gaussian Mixture Model (GMM)-based extracted features from each subject image and a template in the so-defined non-specific region is derived. Our approach to feature extraction consists of using the set of parameters that define the template features, such as weights, covariance matrices and mean vectors to model the remaining images by reducing, consequently their dimensionality. The proposed method is compared to a widely used approach such as specific-to-non-specific binding ratio normalization. This comparison is performed on a DaTSCAN image database comprising analysis and classification stages for the development of a computer aided diagnosis (CAD) system for Parkinsonian syndrome (PS) detection.


[Anesthesia with jet injection. Use of Medi-Jector EZ dermojet for anesthesia in minor surgery].
The local anaesthetic procedure is often painful to the patient. During a period of 21 weeks, jet injection was used as the anaesthetic procedure in 55 cases of minor surgery in a single general practice. The application is discussed, giving a variety of examples. The method provides a simple and almost pain-free anaesthetic procedure in the majority of minor surgical operations. The amount of anaesthetic is reduced. The method is particularly suitable for anaesthetizing sensitive areas like the finger of a child or verrucas.


Aspirin suppresses neuronal apoptosis, reduces tissue inflammation, and restrains astrocyte activation by activating the Nrf2/HO-1 signaling pathway.
The nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element signaling pathway plays a substantial role in preventing oxidative stress-related diseases. Aspirin has been shown to exert several pharmacological effects by inducing the expression of the heme oxygenase-1 (HO-1) protein. However, the effects of aspirin on spinal cord injury (SCI) have rarely been studied. Therefore, we sought to investigate the neuroprotective effects of aspirin after SCI. We employed a spinal cord contusion model in Sprague-Dawley rats, and aspirin was administered intraperitoneally for 7 days. Nissl staining showed that the aspirin treatment significantly reduced the loss of motor neurons after SCI compared with vehicle-treated animals. The expression of Nrf2, quinine oxidoreductase 1, and HO-1 proteins was increased in aspirin-treated animals after SCI compared with the vehicle group. In addition, aspirin simultaneously decreased the expression of inflammation-related proteins, such as tumor necrosis factor-α and interleukin-6 after SCI. Moreover, the ratio of apoptotic neurons in the anterior horn and the levels of the apoptosis-related proteins caspase-3, cleaved caspase-3, and Bax were significantly decreased in the aspirin group compared with the vehicle group. Immunofluorescence staining was used to detect the colocalization of NeuN and HO-1, and the results showed that aspirin significantly increased expression of the HO-1 protein in neurons. In addition, western blots and immunofluorescence staining showed aspirin restrained astrocyte activation. In conclusion, aspirin induces neuroprotective effects by inhibiting astrocyte activation and apoptosis after SCI through the activation of the Nrf2/HO-1 signaling pathway.


Immunoregulatory signal FoxP3, cytokine gene expression and IFN-γ cell responsiveness upon porcine reproductive and respiratory syndrome virus (PRRSV) natural infection.
The study aims at evaluating gene expression of pro-inflammatory (IL-1β, IL-8, TNF-α), pro-immune (IFN-γ), anti-inflammatory (IL-10) cytokines and of the immunoregulatory signal FoxP3 in association with PRRSV-specific IFN-γ secreting cell (SC) responsiveness upon PRRSV natural infection. Forty PRRSV-negative pigs were assigned to two groups: 20 pigs were vaccinated at 3 weeks of age (weaning) against PRRSV (V-PRRSV) with a modified live virus vaccine (MLV) and 20 pigs were kept non-vaccinated (NV) as controls. Blood samples were collected at 3 (vaccination), 6, 8, 10, 12, 14, and 16 weeks of age. Natural infection occurred from 8 weeks of age onward in both groups and viremia lasted 8 weeks. In the early phase of infection, pro-inflammatory cytokines (IL-1β, IL-8, TNF-α) showed a delayed increase concomitant with the peak of viremia in both groups. In both groups, IL-10 peaked at 12 weeks in association with the increase of pro-inflammatory cytokines. Conversely, in vaccinated pigs (V-PRRSV), IFN-γ showed higher gene expression during the early phase of infection and a more intense secreting cell (SC) response in the late phase. Differently, gene expression of the transcription factor FoxP3, expressed by T regulatory lymphocytes (Tregs), increased significantly in controls only and was associated with the rise of the viral load. Moreover, FoxP3 levels remained significantly higher during the late phase of infection and paralleled with lower levels of IFN-γ SC detected by ELISPOT. The expression/production of immunoregulatory signals involved in Treg activation could be a promising marker to study the immunobiology of PRRSV infection.


The kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), decreases morphine withdrawal and the consequent conditioned place aversion in rats.
Much data suggest that the binding of dynorphin-like peptides to kappa-opioid receptors (KORs) during the administration of and withdrawal from a variety of addictive drugs is aversive and serves to limit the reinforcing properties of those drugs and to enhance tolerance, withdrawal, and the probability of stress-induced relapse. In this study, we examined the role of KORs in mediating opioid withdrawal and its aversive consequences in rats. We found that selective blockade of KORs by i.p. administration of 20mg/kg nor-binaltorphimine (nor-BNI) 5h prior to naltrexone-precipitated withdrawal in morphine-dependent rats decreased feces excreted during a 30-min withdrawal session. More critically, this injection of nor-BNI decreased the subsequent conditioned place aversion (CPA) for the withdrawal chamber 2 days later. The subsequent finding that administration of nor-BNI 2h following withdrawal did not affect the CPA 2 days later suggested that nor-BNI reduced the CPA in the prior experiment because it reduced the aversive effects of withdrawal, not because it reduced the aversive/anxiogenic effects of the withdrawal chamber at the time of CPA testing. These data indicate that the binding of dynorphin-like peptides to KORs during opioid withdrawal serves to enhance withdrawal and its aversive consequences and suggest that selective KOR antagonists may be useful in reducing these aversive effects and consequent relapse.


A model for predicting effect of treatment on progression-free survival using MRD as a surrogate end point in CLL.
Our objective was to evaluate minimal residual disease (MRD) at the end of induction treatment with chemoimmunotherapy as a surrogate end point for progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) based on 3 randomized, phase 3 clinical trials (ClinicalTrials.gov identifiers NCT00281918, NCT00769522, and NCT02053610). MRD was measured in peripheral blood (PB) from treatment-naïve patients in the CLL8, CLL10, and CLL11 clinical trials, and quantified by 4-color flow cytometry or allele-specific oligonucleotide real-time quantitative polymerase chain reaction. A meta-regression model was developed to predict treatment effect on PFS using treatment effect on PB-MRD. PB-MRD levels were measured in 393, 337, and 474 patients from CLL8, CLL10, and CLL11, respectively. The model demonstrated a statistically significant relationship between treatment effect on PB-MRD and treatment effect on PFS. As the difference between treatment arms in PB-MRD response rates increased, a reduction in the risk of progression or death was observed; for each unit increase in the (log) ratio of MRD- rates between arms, the log of the PFS hazard ratio decreased by -0.188 (95% confidence interval, -0.321 to -0.055; P = .008). External model validation on the REACH trial and sensitivity analyses confirm the robustness and applicability of the surrogacy model. Our surrogacy model supports use of PB-MRD as a primary end point in randomized clinical trials of chemoimmunotherapy in CLL. Additional CLL trial data are required to establish a more precise quantitative relationship between MRD and PFS, and to support general applicability of MRD surrogacy for PFS across diverse patient characteristics, treatment regimens, and different treatment mechanisms of action.


The peptidyl-prolyl isomerase Pin1 regulates the stability of granulocyte-macrophage colony-stimulating factor mRNA in activated eosinophils.
The infiltration, accumulation and degranulation of eosinophils in the lung represents a hallmark of active asthma. In vivo or in vitro eosinophil activation triggers the secretion of the antiapoptotic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). We now identify Pin1, a cis-trans isomerase, as an essential component of the ribonucleoprotein complex responsible for GM-CSF mRNA stabilization, cytokine secretion and the survival of activated eosinophils. Pin1 regulated the association of the AU-rich element-binding proteins AUF1 and hnRNP C with GM-CSF mRNA, accelerating or slowing decay, respectively. These data indicate Pin1 is a key mediator of GM-CSF production.


Quantal release of serotonin from presynaptic nerve terminals.
Although much is known about the synthesis, storage, break-down and biological importance of serotonin (5-HT) there is little information about its release from presynaptic nerve terminals. For example, in the mammalian CNS it is not known whether 5-HT is released in multimolecular packets (quanta) or whether facilitation of release occurs with successive impulses mobilizing larger numbers of quanta. Other problems concern vesicle recycling after stimulation and the role of calcium entry into presynaptic terminals. Preparations in which such basic questions can be explored directly are provided by individual identified serotonergic neurones isolated from the CNS of a simple invertebrate, the leech. It will be shown that these cells maintain their membrane properties, and continue to synthesize, store and secrete 5-HT in tissue culture. Moreover they make highly specific synaptic connections with certain identified target cells. By a combination of voltage clamp, biochemical and electronmicroscopic techniques it has been shown that serotonin is released in multimolecular packets. The quantal unit size is approx. 15 ?V. Vesicles can be observed to fuse with the presynaptic membrane. With prolonged stimulation vesicle recycling occurs and markers are taken up from extracellular space. Moreover, with trains of impulses, 5-HT release shows clear facilitation, which, as at the neuromuscular junction of the frog, can be explained by the residual calcium hypothesis.


Venovenous extracorporeal membrane oxygenation: early CT alterations following use in management of severe respiratory failure in neonates.
To describe brain CT alterations occurring after neonatal venovenous extracorporeal membrane oxygenation (V-V ECMO). CT studies were prospectively obtained after V-V ECMO in 31 neonates with severe respiratory failure. Images were scored for cerebrospinal fluid space size, hemorrhage, and regions of decreased attenuation. Subarachnoid space enlargement at the interhemispheric fissure, frontal, temporal, or parietal convexity occurred in 21 of the 31 patients. When subarachnoid space enlargement was asymmetric (six of the 21), it was always isolated to or greater on the right. Ventricular enlargement was demonstrated in seven of the 31. Hemorrhage occurred in seven and regions of low brain attenuation in 11 of the 31 neonates. Increased sagittal sinus pressure caused by internal jugular vein ligation and cannulation of the superior vena cava may contribute to subarachnoid space enlargement by decreasing cerebrospinal fluid resorption at the arachnoid villi. Reduced incidence of cerebral hemorrhage with V-V ECMO, as compared with venoarterial (V-A) ECMO, may relate to sparing of the right common carotid artery (it is ligated with V-A ECMO), and to routing of oxygenated blood to the right atrium with V-V ECMO rather than to the arterial circuit as with V-A ECMO.


Quality considerations of paediatric investigation plans for monoclonal antibodies: A regulatory perspective from the MHRA.
Since the advent of the EU Paediatric Regulation in 2007, 78 of the 1688 Paediatric Investigation Plans (PIPs) have been for monoclonal antibodies (Mabs). Of these, 22 have been assessed by the MHRA. The purpose of this mini-review is to aid those researching and developing this class of drugs to better understand regulatory concerns leading to improved medicinal products for children. Three principal quality issues were identified for PIPs under Article 7 and 8: i) the level of anti-aggregation stabilisers, ii) acceptability and tolerability of administration (i.e. multiple injections, infusion time and volume), and iii) the need to develop new presentational forms (e.g. pre-filled syringe). Overall, two types of concerns were ascertained - those which are potentially avoidable (e.g. through development of new presentational forms) and others which require the evolution of new technologies in the sector (e.g. production of concentrated, stabilised preparations).


INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR MACULAR HOLE SURGERY WITHOUT EXTRA MANIPULATION OF THE FLAP.
To determine whether surgical manipulation steps of the internal limiting membrane (ILM) flap, such as ILM trimmed, ILM tuck inside the hole, ILM massage, are mandatory to obtain satisfactory outcomes for the repair of large stage IV idiopathic macular hole using the inverted ILM flap technique. In this interventional comparative prospective single-masked study, 81 eyes were randomized into 2 treatments groups. In Group 1 (41 eyes), the classic inverted ILM flap technique was performed. In Group 2 (40 eyes), a modified procedure was used: after ILM peeling, no extra flap manipulation was performed. The macular hole was covered by the inverted ILM flap because of the air pressure at the time of the fluid-air exchange. At 12 months, macular hole closure was observed in 40 eyes (97.6%) in Group 1 and in 39 eyes in Group 2 (97.5%). U-shape closure rate, ellipsoid zone defects, and external limiting membrane defects were similar in both groups. The results indicate no statistical difference in anatomical and functional success between both groups. The macular hole closure rate, improved visual acuity, and no extra complications indicate noninferiority of the modified inverted ILM technique. Internal limiting membrane finishing, tucking, and massage may not be required to obtain surgical success.


Hans Christian Andersen's spelling and syntax: allegations of specific dyslexia are unfounded.
Sources contemporary with Danish author Hans Christian Andersen claimed that he did not master the Danish language, which modern studies interpret as specific dyslexia. A systematic study of his diaries from age 20 to age 70 found a mean spelling error percentage of approximately 1.7 (SD = 1%, range = 0%-4%). A methodologically independent reliability study confirmed these figures. Andersen's error percentages in poems and letters from ages 11 to 19 show a typical initial part of a learning curve that, together with the results from the diaries, gives a life span curve of his spelling development. The diaries, letters, and poems contain only insignificant syntactic errors. Andersen's spelling in the above studies is compared with that of his contemporaries and with data from modern studies. His mean error percentages at different ages are equal to the figures from nondisabled participants, but between 2 and 15 times lower than the mean percentages in studies of individuals with dyslexia. A structural analysis of Andersen's spelling errors shows that they are mainly phonologically plausible from ages 11 to 70, and that the proportions of plausible/implausible errors match those of normal achievers, but not those of individuals with dyslexia.


Food allergies: immunological reactions to food.
Allergic reactions to food are mediated by the immune system, can be consistently reproduced, and cause a change in the target organ. An estimated 0.3% to 20% of infants are affected. The incidence decreases with age to about 1% to 3% in adults. Development of food allergies depends on heredity, intestinal permeability, immune responsiveness, and exposure to food. Common symptoms include gastrointestinal, skin, or respiratory disturbances that occur from seconds to several hours after food ingestion. Although the skin-prick test is the most reliable diagnostic test, positive results must be followed by a trial elimination diet and food challenge to determine whether symptoms appear after food ingestion. Food allergies are treated by the elimination of the offending foods from the diet. Breast feeding is usually recommended to reduce the incidence of allergic disease in infants. The dietitian's expertise is particularly valuable in assessing the nutritional status of the allergic person, assuring nutritional adequacy during treatment and maintenance, and participating in research to address the many unresolved issues surrounding food allergies.


Overcoming design problems in evaluating health behavior programs.
The increasing importance of high-quality evaluative research on health lifestyle change programs is established. Failure to ask the right evaluative research questions and problems of research design are identified as two major reasons for the dearth of well-controlled, interpretable evaluations in this area. Thirteen issues of research design that need to be considered if interpretable answers to evaluative research questions are to be obtained are identified and discussed. Solutions to these problems and design recommendations are offered.


[Ligament reconstruction for the chronic instability of the traumatic thumb carpometacarpal joint].
We evaluated the results of ligament reconstruction performed for chronic instability of the traumatic thumb carpometacarpal joint. Seven male patients with traumatic instability of the thumb carpometacarpal joint underwent ligament reconstruction with the use of the technique described by Eaton and Littler. The mean duration between the traumatic event and the operation was eight months. According to the radiological criteria by Eaton and Littler, five patients had stage I, and two patients had stage II disease. The mean follow-up period was 23 months. The results were assessed according to the criteria by Lane and Eaton. Postoperatively, the patients' grip strength and pinch strength increased by a mean of 40.4% (range 31% to 50%) and 75.4% (range 62% to 100%), respectively. No increases in the extent of arthrosis were observed in the carpometacarpal joint during the follow-up period. None of the patients developed morbidity associated with the functions of the flexor carpi radialis and the wrist. The results were excellent in four, and good in three patients. No complications occurred such as infection or recurrent instability, nor were there any problems related to the skin and Kirschner wires. Ligament reconstruction for the carpometacarpal joint of the thumb relieves pain and restores stability while preserving a functional range of motion in patients with chronic instability.


Attitudes towards physician-nurse collaboration in a primary care team-based setting: Survey-based research conducted in the chronic care units of the Tuscany region of Italy.
Across the world, multidisciplinary teamwork has become an essential component in the care of patients with chronic conditions--the Chronic Care Units (CCUs) in the Italian region of Tuscany are no exception to this new era of collaboration. We sought to explore the attitudes towards collaboration of general practitioners (GPs) and nurses within the CCUs using the Jefferson Scale of Attitudes towards Physician-Nurse Collaboration (JSAPNC). The survey was sent electronically to 218 GPs and 46 nurses of 23 CCUs in two Local Health Authorities of Tuscany. A higher JSAPNC score is indicative of a more positive attitude towards physician-nurse collaboration. JSAPNC scores were calculated for both totals and by three factors: "shared education and collaboration," "caring versus curing," and "physician authority." A total of 133 healthcare professionals (94 GPs and 39 nurses) responded (response rate = 51.5%). Nurses reported significantly more positive attitudes towards collaboration than GPs (52.5 vs. 44.0, p < 0.01). This trend was also found in each of the three factors. This information adds to the scarce literature on nurse-physician collaboration in the primary care setting and highlights the need for considerable improvement given the rise of team-based outpatient care models.


The effect of overnourishing singleton-bearing adult ewes on nutrient partitioning to the gravid uterus.
Overnourishing the singleton-bearing adolescent sheep throughout pregnancy promotes maternal tissue synthesis at the expense of the nutrient requirements of the gravid uterus. Consequently, the growth of the placenta is impaired and results in the premature delivery of low-birth-weight lambs relative to moderately fed adolescents of equivalent age. To establish if this phenomenon is unique to the growing animal, singleton pregnancies to a single sire were established by embryo transfer into primiparous adult ewes who had attained the normal mature body size for their genotype. Thereafter ewes were offered a maintenance or a high level of a complete diet throughout gestation. High maternal intakes resulted in elevated maternal insulin, no significant change in growth hormone or glucose, and attenuated progesterone and NEFA concentrations. Live weight gain during the first 93 d of gestation was 48 and 244 g/d, and adiposity score at term was 2.4 and 3.7 in the maintenance and high groups, respectively (P<0.001). In spite of achieving levels of adiposity similar to overnourished adolescents, placental (477 (sem 30) v. 518 (sem 41) g) and fetal (5190 (sem 320) v. 5420 (sem 250) g) weights were equivalent in maintenance and high groups. Gestation length was shorter (P<0.01) and colostrum yield at parturition lower (P<0.05) in high v. maintenance dams. Thus, adult sheep appear to be relatively insensitive to the oversupply of nutrients during pregnancy and have the ability to meet the nutrient requirements for normal conceptus growth in spite of their increased adiposity.


Effect of excess extracellular glutamate on dendrite growth from cerebral cortical neurons at 3 days in vitro: Involvement of NMDA receptors.
Glutamate is an important regulator of dendrite development; however, during cerebral ischemia, massive glutamate release can lead to neurodegeneration and death. An early consequence of glutamate excitotoxicity is dendrite injury, which often precedes cell death. We examined the effect of glutamate on dendrite growth from embryonic day 18 (E18) mouse cortical neurons grown for 3 days in vitro (DIV) and immunolabeled with anti-microtubule-associated protein (MAP)2 and anti-neurofilament (NF)-H, to identify dendrites and axons, respectively. Cortical neurons exposed to excess extracellular glutamate (100 microM) displayed reduced dendrite growth, which occurred in the absence of cell death. This effect was mimicked by the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) and blocked by the ionotropic glutamate receptor antagonist kynurenic acid and the NMDA receptor-specific antagonist MK-801. The non-NMDA receptor agonist AMPA, however, did not affect process growth. Neither NMDA nor AMPA influenced neuron survival. Immunolabeling and Western blot analysis of NMDA receptors using antibodies against the NR1 subunit, demonstrated that immature cortical neurons used in this study, express NMDA receptors. These results suggest that excess glutamate decreases dendrite growth through a mechanism resulting from NMDA receptor subclass activation. Furthermore, these data support the possibility that excess glutamate activation of NMDA receptors mediate both cell death in mature neurons and the inhibitory effect of excess glutamate on dendrite growth in immature neurons or in the absence of cell death.


Effect of atomic disorder on the magnetic phase separation.
The effect of disorder on the magnetic phase separation between the antiferromagnetic and incommensurate helical [Formula: see text] and [Formula: see text] phases is investigated. The study is based on the quasi-two-dimensional single-band Hubbard model in the presence of atomic disorder (the [Formula: see text] Anderson-Hubbard model). A model of binary alloy disorder is considered, in which the disorder is determined by the difference in energy between the host and impurity atomic levels at a fixed impurity concentration. The problem is solved within the theory of functional integration in static approximation. Magnetic phase diagrams are obtained as functions of the temperature, the number of electrons and impurity concentration with allowance for phase separation. It is shown that for the model parameters chosen, the disorder caused by impurities whose atomic-level energy is greater than that of the host atomic levels, leads to qualitative changes in the phase diagram of the impurity-free system. In the opposite case, only quantitative changes occur. The peculiarities of the effect of disorder on the phase separation regions of the quasi-two-dimensional Hubbard model are discussed.


Surgeon--assistant communication.
Although conflict is often viewed negatively, in reality, patient care can be enhanced by a combination of conflict and collaborative techniques. Strategic timing, along with an appropriate location for the interaction, is important in resolving a disagreement. A defensive approach will only cause an interaction to escalate--use a calm, objective approach instead.


A study of brain white matter plasticity in early blinds using tract-based spatial statistics and tract statistical analysis.
Early blind individuals are known to exhibit structural brain reorganization. Particularly, early-onset blindness may trigger profound brain alterations that affect not only the visual system but also the remaining sensory systems. Diffusion tensor imaging (DTI) allows in-vivo visualization of brain white matter connectivity, and has been extensively used to study brain white matter structure. Among statistical approaches based on DTI, tract-based spatial statistics (TBSS) is widely used because of its ability to automatically perform whole brain white matter studies. Tract specific analysis (TSA) is a more recent method that localizes changes in specific white matter bundles. In the present study, we compare TBSS and TSA results of DTI scans from 12 early blind individuals and 13 age-matched sighted controls, with two aims: (a) to investigate white matter alterations associated with early visual deprivation; (b) to examine the relative sensitivity of TSA when compared with TBSS, for both deficit and hypertrophy of white matter microstructures. Both methods give consistent results for broad white matter regions of deficits. However, TBSS does not detect hypertrophy of white matter, whereas TSA shows a higher sensitivity in detecting subtle differences in white matter colocalized to the posterior parietal lobe.


Effect of the distribution of radioactive sources on deadtime loss in a single-crystal gamma camera.
Quantitative studies with a single-crystal gamma camera often require correction for deadtime count loss. We evaluated the deadtime characteristics of a gamma camera using point sources. Point sources with various radioactivities were measured, and the relation between radioactivity and count rate was assessed. Two sources with different activities were imaged apart or adjacent to each other, and the effect of the geometrical distribution on counting efficiency was investigated. Count loss was increased at a high radioactivity level, and was well corrected using a nonparalyzable model and a deadtime of 4.99 microsec. It was not affected by the distance between the two sources, and occurred equally for the two sources imaged together. The count loss in imaging two sources was successfully corrected by multiplying the obtained image by a correction factor based on the count rate in the whole field-of-view. These results support the reliability of the analytic technique for deadtime correction.


[Iatrogenic diffuse interstitial pneumonia linked to 5-aminosalicylate].
Iatrogenic pneumonias to sulphasalazine are most usually seen during the course of a haemorrhagic proctocolitis (RCH). We report a case in which a young woman was treated with 5-aminosalicylate (Pentasa) and prednisolone during an exacerbation of RCH. After 3 months of treatment the steroid therapy was stopped and the Pentasa was continued at the same dose (3 g per day). She presented with increasing dyspnoea on effort. Clinical examination was normal but a CT scan of the chest showed interstitial micro nodules; there was also a restrictive ventilatory disorder, hypoxaemia on effort and an alveolar eosinophilia (1.8%) The clinical progress, respiratory and blood gases all improved rapidly after stopping the Pentasa with the disappearance of the interstitial nodule over 5 months, suggesting that the role of the Pentasa was causal in the genesis of the pneumonia.


Insights into the subsurface transport of As(V) and Se(VI) in produced water from hydraulic fracturing using soil samples from Qingshankou Formation, Songliao Basin, China.
Produced water is a type of wastewater generated from hydraulic fracturing, which may pose a risk to the environment and humans due to its high ionic strength and the presence of elevated concentrations of metals/metalloids that exceed maximum contamination levels. The mobilization of As(V) and Se(VI) in produced water and selected soils from Qingshankou Formation in the Songliao Basin in China were investigated using column experiments and synthetic produced water whose quality was representative of waters arising at different times after well creation. Temporal effects of produced water on metal/metalloid transport and sorption/desorption were investigated by using HYDRUS-1D transport modelling. Rapid breakthrough and long tailings of As(V) and Se(VI) transport were observed in Day 1 and Day 14 solutions, but were reduced in Day 90 solution probably due to the elevated ionic strength. The influence of produced water on the hydrogeological conditions (i.e., change between equilibrium and non-equilibrium transport) was evidenced by the change of tracer breakthrough curves before and after the leaching of produced water. This possibly resulted from the sorption of polyacrylamide (PAM (-CH2CHCONH2-)n) onto soil surfaces, through its use as a friction reducer in fracturing solutions. The sorption was found to be reversible in this study. Minimal amounts of sorbed As(V) were desorbed whereas the majority of sorbed Se(VI) was readily leached out, to an extent which varied with the composition of the produced water. These results showed that the mobilization of As(V) and Se(VI) in soil largely depended on the solution pH and ionic strength. Understanding the differences in metal/metalloid transport in produced water is important for proper risk management.