Discoid meniscus in children and adolescents: Correlation between morphology and meniscal tears.
Some authors have suggested that the diminished vascular blood supply, peripheral stability and thickness of the discoid meniscus (DM) would make it more prone to tears. The aims of this study are two-fold: 1) To analyse morphological characteristics by magnetic resonance (MRI), and 2) To correlate the size of the meniscus with the presence of meniscal tears. The MRI of patients ≤18 years-old over a period of 5 years were reviewed, and patients with DM were identified. We analysed demographic data, location (medial or lateral), morphology (Watanabe), meniscal tears (Crues classification), pattern, displacement, and other associated findings. Meniscal height and thickness per width (TxW) were also calculated. The correlation between variables: morphology, height and TxW with the presence of meniscal tears were statistically analysed. Six hundred and eighty-five MRI (675 patients) were analysed. Forty-three knees (38 patients, 20 males) were found to have a DM (6.3%). The average age was 12.2±3.8 years (range: 4-18 years). Sixty-three percent had some type of meniscal injury. Patients with complete MD had a higher incidence of injuries (77.3 vs. 47.6%; P=.001). Longitudinal (bucket handle) and complex tears (n ??=11) only occurred in patients with complete DM. DM with tears presented a nonsignificant tendency to have higher meniscal height and higher TxW (6.29±1.26 vs 5.75±.66mm; P=.20 and 107.5±36.02 vs. 91.54±16.5mm2; P=.162). The results of this series support the theory that a larger meniscal size would be one of the main predisposing factors for the DM to be injured. Cross-sectional study (Level of evidence: III).


Cellulose nanofibrils for one-step stabilization of multiple emulsions (W/O/W) based on soybean oil.
Cellulose nanofibrils (CNF) were incorporated in water-in-oil (W/O) microemulsions and emulsions, as well as water-in-oil-in-water (W/O/W) multiple emulsions using soybean oil. The addition of CNF to the aqueous phase expanded the composition range to obtain W/O/W emulsions. CNF also increased the viscosity of the continuous phase and reduced the drop size both of which increased the stability and effective viscosity of the emulsions. The effects of oil type and polarity on the properties of the W/O/W emulsions were tested with limonene and octane, which compared to soybean oil produced a smaller emulsion drop size, and thus a higher emulsion viscosity. Overall, CNF are a feasible alternative to conventional polysaccharides as stability enhancers for normal and multiple emulsions that exhibit strong shear thinning behavior.


Metrics on multilabeled trees: interrelationships and diameter bounds.
Multilabeled trees or MUL-trees, for short, are trees whose leaves are labeled by elements of some nonempty finite set X such that more than one leaf may be labeled by the same element of X. This class of trees includes phylogenetic trees and tree shapes. MUL-trees arise naturally in, for example, biogeography and gene evolution studies and also in the area of phylogenetic network reconstruction. In this paper, we introduce novel metrics which may be used to compare MUL-trees, most of which generalize well-known metrics on phylogenetic trees and tree shapes. These metrics can be used, for example, to better understand the space of MUL-trees or to help visualize collections of MUL-trees. In addition, we describe some relationships between the MUL-tree metrics that we present and also give some novel diameter bounds for these metrics. We conclude by briefly discussing some open problems as well as pointing out how MUL-tree metrics may be used to define metrics on the space of phylogenetic networks.


The role of NOS in the impairment of spatial memory and damaged neurons in rats injected with amyloid beta 25-35 into the temporal cortex.
The Aβ(25-35) fraction mimics the toxic effects of the complete peptide Aβ(1-42) because this decapeptide is able to cause memory impairment and neurodegenerative events. Recent evidence has shown that the injection of Aβ(25-35) into the temporal cortex (TCx) of the rat increases the nitric oxide (NO) pathways with several consequences, such as neuronal loss in rats. Our aim was to investigate the effects of each NOS isoform by the prior injection of NOS inhibitors before the injection of the Aβ(25-35). One month after the treatment, the animals were tested for their spatial memory in the radial maze. The hippocampus (Hp) and TCx were assessed for NO production, nitration of proteins (3-NT), astrocytosis (GFAP), and neuronal loss. Our findings show a significant impairment in the memory caused by Aβ25-35 injection. In contrast NOS inhibitors plus Aβ25-35 cause a protection yielding a high performance in the memory test and reduction of cell damage in the TCx and the Hp. Particularly, iNOS is the major source of NO and related to the inflammatory response leading to the memory deficits. The inhibition of iNOS is an important target for neuronal protection against the toxicity of the Aβ25-35 over the long term.


Analytic evaluation and application of a novel spectrophotometric serum lithium method to a rapid response laboratory.
The authors present an evaluation of the Lithium DST spectrophotometric method developed by Thermotrace (Victoria, Australia) on a Hitachi 917 analyzer. Accuracy was assessed by method comparison with an ion-selective electrode (ISE; Roche Integra 700) (n = 80). Linearity, within-run and between-run precision, and susceptibility to interference by hemolysis, icterus, lipemia, and sodium were assessed. The method was linear to 3.0 mM/L, and analyzer auto-dilution extended the reportable range to 7.2 mmol/L. Within-run coefficient of variation was 1.5% at 0.68 mmol/L and 0.7% at 2.06 mM/L. Between-run precision for the same lithium concentrations assayed daily for 20 days were 3.1% and 1.9%, respectively. Method agreement with ISE was excellent, with an intercept of 0.000 and slope of 1.000 by Passing Bablock regression analysis. Hemolysis, icterus, lipemia, and high and low sodium levels did not significantly interfere. The manufacturer's recommended calibration stability of 1 week was confirmed. The authors conclude that this method is reliable, accurate, and precise. The Thermotrace serum lithium spectrophotometric method provides a useful alternative to ISE or flame photometry, facilitates workstation consolidation on the Hitachi 917 multiple-channel analyzer, and is well adapted for use in a rapid response laboratory.


Atriopeptin 2 is hydrolysed by cardiac but not pulmonary isozyme of angiotensin-converting enzyme.
Hydrolysis of Bz-Gly-Ser-Phe-Arg, C-terminal fragment of atriopeptin 2, by human cardiac angiotensin-converting enzyme has been studied. The KM for the reaction was 10(-4) M. The effect of concentration of NaCl on activity of cardiac angiotensin-converting enzyme has been determined, which allowed to regard Bz-Gly-Ser-Phe-Arg as bradykinin-like substrates. It was demonstrated that cardiac, but not pulmonary isozyme of angiotensin-converting enzyme specifically hydrolyses atriopeptin 2.


Occurrence and exposure assessment of bisphenol analogues in source water and drinking water in China.
Bisphenol analogues (BPs) are widely used in the production of epoxy resins and polycarbonate plastics. In recent years, the demand and production capacity of BPs are growing rapidly in China. However, knowledge on the occurrence of BPs other than bisphenol A (BPA) in the aquatic environment, especially in source and drinking water, is still limited. In this study, occurrence of 16 BPs, which have been used in various industrial applications, was investigated in source and drinking water from twenty drinking water treatment plants (DWTPs) across China. In source water, BPA, bisphenol AF (BPAF), bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF), and bisphenol S (BPS) were detected at the following concentration ranges: BPA (n.d.-34.9 ng/L), BPAF (n.d.-10.8 ng/L), BPB (n.d.-14.3 ng/L), BPE (n.d.-6.2 ng/L), BPF (n.d.-12.6 ng/L), and BPS (n.d.-5.2 ng/L). In drinking water BPA, BPAF, BPB, BPE, BPF, and BPS were detected as follows: BPA (n.d. - 6.5 ng/L), BPAF (n.d.-4.7 ng/L), BPB (n.d.-3.2 ng/L), BPE (n.d.-0.6 ng/L), BPF (n.d.-0.9 ng/L), and BPS (n.d.-1.6 ng/L). In addition, to assess the exposure of BPs through drinking water consumption, the estimated daily intake of each detected BPs was calculated. The estimated daily intake (EDIs) was below 0.25 ng/kg bw/day for each detected BPs, much lower than the tentative oral reference dose (RfD) values for BPA (4 μg/kg bw/day) recommended by the European Food Safety Authority.


Antiadhesive effect of bioresorbable polylactide film in abraded middle ear mucosa.
Polylactide film (PLF) is used to prevent postoperative peridural adhesion in spinal surgery. Up until now, the antiadhesive effect of bioresorbable PLF in ear middle surgery has not been reported. The purpose of this study is to evaluate the antiadhesive effect of PLF in guinea pigs serving as a model for middle ear mucosal trauma. The animals were divided into two groups: the PLF group and the silastic sheeting group. There were seven guinea pigs (fourteen ears) in both groups. Under aseptic conditions, the middle ear mucosa was abraded using a pick inserted transbullaly. A PLF or silicone sheet was then placed into the guinea pigs' middle ear cavities. The auditory brainstem responses (ABRs) were assessed preoperatively and at three weeks postoperatively while the animals were under general anesthesia. A histopathological study was performed 3 weeks after the operation. The difference between the ABR results before the operation and three weeks postoperatively were not statistically significant. The adhesion formation did not appeared in either group. Prominent fibrous capsule formation and inflammation were observed in the silastic sheeting group, but not in the PLF group. Mild fibrous thickening of regenerated mucosa was observed in the PLF group. From our results, bioresorbable PLF is nonototoxic and biocompatible with the guinea pig's middle ear cavity by short-term evaluation. Further long-term evaluation study is necessary before clinical application.


Classifying episodes in schizophrenia and bipolar disorder: criteria for relapse and remission applied to recent-onset samples.
Research on predicting and preventing episodes of schizophrenia and mood disorder lacks consistent, specific definitions of episodes. We present an operational system for identifying relapse, exacerbation, and remission of schizophrenia and bipolar disorder within longitudinal studies that involve repeated symptom assessments. Three major classes of episodic outcome are defined: relapse or significant exacerbation, nonrelapse, and stable, severe persisting symptoms. These major classes are further subdivided to distinguish nine categories of episodic outcome. To examine ease of use, interrater reliability, and validity, the classification system was applied to recent-onset samples of schizophrenia patients (N=77) and bipolar mood disorder patients (N=23) followed on medication for 9- to 12-month periods. A range of episodic outcomes were distinguished with high interrater reliability. Despite being prescribed continuous medication, 21% of the recent-onset schizophrenia patients and 61% of bipolar patients met criteria for relapse or significant exacerbation during this follow-up period. Predictive relationships support the validity of this system for classifying episodes. A computer program is available to facilitate its use. Use of these explicit definitions of episodes may help to clarify the relationship between episodic outcome and other fundamental domains of illness outcome, particularly other symptom dimensions, work functioning, and social functioning.


Problematic video game use as an emotional coping strategy: Evidence from a sample of MMORPG gamers.
A positive relationship between problematic gaming and escapism motivation to play video games has been well established, suggesting that problematic gaming may result from attempts to deal with negative emotions. However, to date, no study has examined how emotion dysregulation affects both escapism motives and problematic gaming patterns. Difficulties in emotion regulation, escapism, and problematic involvement with video games were assessed in a sample of 390 World of Warcraft players. A structural equation modeling framework was used to test the hypothesis that escapism mediates the relationship between emotion dysregulation and problematic gaming. Statistical analyses showed that difficulties in emotion regulation predicted both escapism motives and problematic gaming, and that escapism partially mediated this relationship. Our findings support the view that problematic players are likely to escape in online games as a maladaptive coping strategy for dealing with adverse emotional experiences.


Time course of leukocyte adhesion to endothelium in ischemia-reperfusion.
Adhesion of leukocytes (L) to microvascular endothelium (E) is a required step in the L-E interaction leading to tissue injury in ischemia-reperfusion. To assess the optimum period for therapy aimed at ameliorating negative effects of this required step, we investigated the time course of L-E adhesion in the hamster cheek pouch using 2 hr of ischemia and 1 hr of reperfusion in our model of I-R injury (Am. J. Physiol-261: 1626, 1991). Leukocytes adhering (stationary for > or = 30 sec) to postcapillary venules (15-30 microns in diameter) were counted after labeling with acridine orange. Prior to the induction of ischemia, there were no significant differences in the number of adherent leukocytes in each area chosen for study (1.9 +/- 0.6 vs 2.0 +/- 0.3; mean number of leukocytes/100-microns vessel length +/- SD). After 10 and 20 min of reperfusion there was no significant difference in leukocyte adhesion in the ischemic area relative to the control (2.7 +/- 0.5 vs 2.8 +/- 0.8, and 5.3 +/- 2.8 vs 2.4 +/- 0.6, respectively). Leukocyte adherence increased significantly after 30 min of reperfusion and remained elevated at 1 hr of reperfusion in the postischemic area relative to the nonischemic control area (7.8 +/- 1.3 vs 3.6 +/- 0.6, and 8.3 +/- 0.8 vs 4.1 +/- 0.6, respectively; P < 0.01). Leukocyte adhesion in the postischemic area after 30 min reperfusion was not significantly different from the adhesion at the end of 1 hr reperfusion. These data suggest that (1) peak leukocyte adhesion occurs after 30 min of normal reperfusion and (2) postischemic therapeutic intervention may be most beneficial when instituted within this early time period.


Effect of shock waveform on relationship between upper limit of vulnerability and defibrillation threshold.
The upper limit of vulnerability (ULV) correlates with the defibrillation threshold (DFT). The ULV can be determined with a single episode of ventricular fibrillation and is more reproducible than the single-point DFT. The critical-point hypothesis of defibrillation predicts that the relation between the ULV and the DFT is independent of shock waveform. The principal goal of this study was to test this prediction. We studied 45 patients at implants of pectoral cardioverter defibrillators. In the monophasic-biphasic group (n = 15), DFT and ULV were determined for monophasic and biphasic pulses from a 120-microF capacitor. In the 60- to 110-microF group (n = 30), DFT and ULV were compared for a clinically used 110-microF waveform and a novel 60-microF waveform with 70% phase 1 tilt and 7-msec phase 2 duration. In the monophasic-biphasic group, all measures of ULV and DFT were greater for monophasic than biphasic waveforms (P < 0.0001). In the 60- to 110-microF group, the current and voltage at the ULV and DFT were higher for the 60-microF waveform (P < 0.0001), but stored energy was lower (ULV 17%, P < 0.0001; DFT 19%, P = 0.03). There was a close correlation between ULV and DFT for both the monophasic-biphasic group (monophasic r2 = 0.75, P < 0.001; biphasic r2 = 0.82, P < 0.001) and the 60- to 110-microF group (60 microF r2 = 0.81 P < 0.001; 110 microF r2 = 0.75, P < 0.001). The ratio of ULV to DFT was not significantly different for monophasic versus biphasic pulses (1.17 +/- 0.12 vs 1.14 +/- 0.19, P = 0.19) or 60-microF versus 110-microF pulses (1.15 +/- 0.16 vs 1.11 +/- 0.14, P = 0.82). The slopes of the ULV versus DFT regression lines also were not significantly different (monophasic vs biphasic pulses, P = 0.46; 60-microF vs 110-microF pulses, P = 0.99). The sample sizes required to detect the observed differences between experimental conditions (P < 0.05) were 4 for ULV versus 6 for DFT in the monophasic-biphasic group (95% power) and 11 for ULV versus 31 for DFT in the 60- to 110-microF group (75% power). The relation between ULV and DFT is independent of shock waveform. Fewer patients are required to detect a moderate difference in efficacy of defibrillation waveforms by ULV than by DFT. A small-capacitor biphasic waveform with a long second phase defibrillates with lower stored energy than a clinically used waveform.


Preoperative aspirin therapy is associated with improved postoperative outcomes in patients undergoing coronary artery bypass grafting.
Aspirin is beneficial in the setting of atherosclerotic cardiovascular disease. There are limited data evaluating preoperative aspirin administration preceding coronary artery bypass grafting and associated postoperative outcomes. Using prospectively collected data from 1636 consecutive patients undergoing first-time isolated coronary artery bypass surgery at our institution from January 2000 through December 2002, we evaluated the association between aspirin usage within the 5 days preceding coronary bypass surgery and risk of adverse in-hospital postoperative events. A logistic regression model, which included propensity scores, was used to adjust for remaining differences between groups. Overall, there were 36 deaths (2.2%) and 48 adverse cerebrovascular events (2.9%) in the postoperative hospitalization period. Patients receiving preoperative aspirin (n=1316) had significantly lower postoperative in-hospital mortality compared with those not receiving preoperative aspirin [1.7% versus 4.4%; adjusted odds ratio (OR), 0.34; 95% CI, 0.15 to 0.75; P=0.007]. Rates of postoperative cerebrovascular events were similar between groups (2.7% versus 3.8%; adjusted OR, 0.67; 95% CI, 0.32 to 1.50; P=0.31). Preoperative aspirin therapy was not associated with an increased risk of reoperation for bleeding (3.5% versus 3.4%; P=0.96) or requirement for postoperative blood product transfusion (adjusted OR, 1.17; 95% CI, 0.88 to 1.54; P=0.28). Aspirin usage within the 5 days preceding coronary artery bypass surgery is associated with a lower risk of postoperative in-hospital mortality and appears to be safe without an associated increased risk of reoperation for bleeding or need for blood product transfusion.


Transsacral approach to repair of rectal prolapse in children.
Rectal prolapse is not uncommon in the pediatric age group. Occurring more frequently in boys than girls and most often during the period of toilet training, the condition is usually self-limited. Treatment typically consists of nonoperative measures. There are patients, however, in whom operative intervention becomes necessary. Operative procedures described are based largely on adult experience and the most common repairs involve the use of a foreign body (Ripstein procedure) or colonic resection. These procedures are of considerable magnitude and may be attended by significant morbidity. As a result, there is reluctance to apply these techniques in children. There exists, then, a place for an efficacious method of repair for large prolapses that incurs minimal morbidity. This report recounts our experience with the treatment of four children with rectal prolapse using a transsacral rectopexy. The results indicate minimal perioperative morbidity, discharge within a few days, with the mechanisms of fecal continence being preserved. The longest follow-up is 17 years with a mean follow-up of 9 years. The overall treatment of rectal prolapse in children is reviewed with specific emphasis upon the indications for and technique of the transsacral approach.


Identification of human papillomavirus DNA in cutaneous lesions of Cowden syndrome.
Cowden syndrome (CS) or multiple hamartoma syndrome is a cancer-associated genodermatosis inherited in an autosomal dominant pattern. One of the diagnostic criteria is facial papules which are felt to be trichilemmomas, benign hair follicle tumors, which some consider to be induced by human papillomavirus (HPV). To search for HPV in skin tumors, especially trichilemmomas, from patients with CS. Skin lesions from patients with CS were classified histologically. Each tumor was then analyzed for HPV DNA by polymerase chain reaction with different primer sets; positive amplicons were typed by direct sequencing. Twenty-nine biopsies from 7 patients with CS were investigated. Only 2 of 29 tumors clinically suspected of being trichilemmomas were confirmed histologically. In addition, 3 sclerotic fibromas, also typical of CS, were found, as well as 1 sebaceous hyperplasia. The other 23 lesions showed histological features of HPV- induced tumors in various stages of development. HPV DNA was found in 19 of 29 cutaneous lesions. Tumors without any histological signs of HPV induction were negative for HPV DNA. Two tumors which were histologically classified as common warts contained HPV types 27 and 28. All the 17 other HPV types belong to the group of epidermodysplasia-verruciformis-associated types. The majority of cutaneous lesions in CS contain HPV DNA. They may have a variety of histological patterns. Trichilemmomas are not clinically distinctive and can be difficult to identify in CS patients.


Economic Evaluation of Linaclotide for the Treatment of Adult Patients With Chronic Idiopathic Constipation in the United States.
To evaluate the effectiveness and costs of linaclotide (Linzess) versus lubiprostone (Amitiza) in the treatment of adult patients with chronic idiopathic constipation (CIC). A decision-tree model using model inputs derived from published literature, linaclotide phase 3 trial data, and a physician survey. Measures of treatment efficacy were selected based on comparability between trial data, with posthoc analyses of linaclotide required to ensure comparability with available lubiprostone data. Response to therapy was defined as (1) having one of the best two satisfaction answers of a 5-point global treatment satisfaction scale at Week 4 or (2) having a weekly spontaneous bowel movement (SBM) frequency 4 at Week 4. Patients who do not respond to therapy are assumed to accrue costs associated with a treatment failure. Model time horizon is aligned with the lubiprostone clinical trial duration of 4 weeks. Model outputs include response rates, quality-adjusted life-years (QALYs) and direct costs. Linaclotide was associated with lower per-patient costs vs lubiprostone for both definitions of response ($946 vs $1,015 for global assessment and $727 vs $737 for SBM frequency). When treatment response was based on a global assessment of treatment satisfaction, linaclotide was associated with higher effectiveness (response: 39.3% vs 35.0%). For SBM frequency, linaclotide was slightly less effective compared to lubiprostone (response: 58.6% vs 59.6%), but also less costly. Base-case results were robust in sensitivity analysis. Linaclotide is less expensive with similar effectiveness when compared to lubiprostone for the treatment of CIC in adult patients.


Treatment of articulatory impairment in a child with spastic dysarthria associated with cerebral palsy.
A comparative study of treatment modalities for improving articulation in a 13-year-old child with severe spastic dysarthria associated with spastic cerebral palsy (SCP) was conducted. A multiple treatment design examined the effect of phonetic placement therapy (PPT) and sEMG-facilitated biofeedback relaxation therapy over a 6-week period. Treatment outcomes were measured using acoustic and perceptual analysis. Results revealed significant improvement in single word intelligibility following PPT with the improvements maintained following sEMG treatment. sEMG-facilitated biofeedback relaxation treatment indicated the occurrence of a pre-cursor skill in increased motor control. Intelligibility at paragraph or sentence level did not change following either treatment. Perceptually, there was no change to any parameters of articulation following either treatment. However, subtle changes were observed on acoustic analysis. Functionally, the participant reported no changes to feelings of well-being or distress regarding her speech disorder over the period of intervention. Clinically, the PPT and sEMG treatments demonstrated improvement in single word articulation, despite no perceptible changes to overall intelligibility. It is likely that the severity of the participant's dysarthria was a factor in the minimal changes observed following treatment. Future studies examining the treatments in children with mild and/or moderate dysarthria are required.


Gingival crevicular fluid interleukin-36β (-1F8), interleukin-36γ (-1F9) and interleukin-33 (-1F11) levels in different periodontal disease.
Periodontal inflammation is driven by the coordinated action of a number of factors, including the IL-1 family. Our study aimed to examine the levels of interleukin (IL)-36β, IL-36γ and IL-33 levels in gingival crevicular fluid (GCF) from patients with different periodontal diseases. A total of 80 subjects, 20 patients with generalized aggressive periodontitis (G-AgP), 20 patients with chronic periodontitis (CP), 20 with gingivitis and 20 periodontally healthy subjects were included. Periodontal status was evaluated by measuring probing depth, clinical attachment loss, papillary bleeding index and plaque index. GCF cytokine levels were analysed by ELISA. CP, gingivitis and healthy groups had similar GCF IL-36β total amount (p>0.008). G-AgP group had elevated IL-36β total amount compared to CP group (p<0.008). G-AgP group had similar GCF IL-36β total amount to gingivitis and healthy groups (p>0.008). GCF IL-36γ and IL-33 total amounts of the study groups were similar (p>0.05). The present study demonstrated for the first time the presence of IL-36β, IL-36γ and IL-33 GCF levels with different periodontal diseases. High levels of IL-36-β in the AgP group in comparison to CP group might suggest that periodontitis in the aggressive form could be related to the increase in GCF IL-36β.


Therapeutic controversies: tumor necrosis factor α inhibitors in ankylosing spondylitis.
Tumor necrosis factor α inhibitors (TNF blockers) have revolutionized the treatment of patients with anklyosing spondylitis. Despite clinical efficacy, there are questions and controversies treating rheumatologists face, which this review discusses: whether there are specific indications for specific TNF blockers; whether the dose of TNF blockers can be decreased; whether immunogenicity plays a role; what the role of residual active inflammation MRI might be; and whether there is a window of opportunity to treat patients with anklyosing spondylitis and prevent radiographic progression. This article summarizes evidence for switching between TNF blockers and addresses the question of malignancies.


An efficient analysis of nanomaterial cytotoxicity based on bioimpedance.
In the emerging nanotechnology field, there is an urgent need for the development of a significant and sensitive method that can be used to analyse and compare the cytotoxicities of nanomaterials such as carbon nanotubes (CNTs) and gold nanoparticles (AuNPs), since such materials can be applied as contrast agents or drug delivery carriers. The bioimpedance system possesses great potential in many medical research fields including nanotechnology. Electric cell-substrate impedance sensing (ECIS) is a particular bioimpedance system that offers a real-time, non-invasive, and quantitative measurement method for the cytotoxicity of various materials. The present work compared the cytotoxicity of AuNPs to that of purchased single-walled carbon nanotubes (SWCNTs). The size-controlled and monodispersed AuNPs were synthesized under autoclaved conditions and reduced by ascorbic acid (AA) whereas the purchased SWCNTs were used without any surface modifications. Bioimpedance results were validated by conventional WST-1 and trypan blue assays, and transmission electron microscopy (TEM) and field emission scanning electron microscopy (FE-SEM) were performed to examine nanomaterials inside the VERO cells. This research evaluates the ability of the ECIS system compared to those of conventional methods in analyzing the cytotoxicity of AuNPs and SWCNTs with higher sensitivity under real-time conditions.


Influence of the galloyl moiety in tea catechins on binding affinity for human serum albumin.
The major catechins of green tea extract are (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)-epigallocatechin gallate (EGCg). Recent research has indicated that catechins form complexes with human serum albumin (HSA) in blood, and differences in their binding affinity toward HSA are believed to modulate their bioavailability. In this study, we kinetically investigated the interaction between the catechins and HSA immobilized on a quartz-crystal microbalance (QCM). The association constants obtained from the frequency changes of QCM revealed interactions of ECg and EGCg with HSA that are 100 times stronger than those of EC and EGC. Furthermore, comparisons of these catechins by native-gel electrophoresis/blotting with redox-cycling staining revealed that, in a phosphate buffer, ECg and EGCg have a higher binding affinity toward HSA than EC and EGC. These observations indicate that catechins with a galloyl moiety have higher binding affinities toward HSA than catechins lacking a galloyl moiety.


Accuracy of US-guided FNA of focal liver lesions in dogs: 140 cases (2005-2008).
Medical records from dogs having abdominal ultrasound (US) performed between March 2005 and October 2008 were reviewed for detection of focal liver lesions (FLL) with both cytologic and histologic sampling. Samples were classified as to either the presence or absence of major categories of pathologic processes, including malignant neoplasia, inflammation, hyperplasia/benign neoplasia, vacuolar change, extramedullary hematopoeisis, cholestasis, necrosis, and no microscopic abnormalities. Evaluation of selection bias was performed by review of the relative distribution of cytologic diagnoses for cases with histology compared with cases excluded from the comparison analysis because histology results were not available. Cytology had the highest sensitivity for vacuolar change (57.9%), followed by neoplasia (52.0%). Cytology had the highest positive predictive value (PPV) for neoplasia (86.7%) followed by vacuolar change (51.6%). Cytology had lower sensitivity and PPVs for inflammation, necrosis, and hyperplasia. The ability of cytology to characterize disease in canine FLL varies by pathologic process. Clinicians can have a high degree of confidence when a cytologic diagnosis of neoplasia is given; however, cytology is less reliable for excluding the potential for neoplasia. Cytology has a low sensitivity and PPV for inflammation and a limited diagnostic performance for the diagnosis of vacuolar change.


Rippling muscle disease: evidence for phenotypic and genetic heterogeneity.
We describe the clinical features of a family with rippling muscle disease. Muscle stiffness and myalgia were the most prominent symptoms. Muscle rippling, although distinctive, was present in only 6 of the 11 affected family members, whereas persistent muscle contraction to muscle percussion was present in all affected adults. Although this persistent contraction resembled percussion myotonia, it was electrically silent and is therefore more aptly called "percussion contracture." We also observed two clinical features not emphasized in previously reported kindreds: mild but asymptomatic weakness of face or proximal muscles was present in 5 of 11 affected members, and 5 individuals also complained of toe walking after a prolonged period of inactivity, reflecting the disproportionate involvement of the calf muscles. The pedigree suggested autosomal dominant inheritance. Our linkage analysis excluded the region on chromosome 1q identified in a previous linkage study.


[Effect of sodium dipropylacetate on experimental convulsions produced by pentetrazole and picrotoxin].
Sodium dipropylacetate, an anticonvulsant used in human therapy, gives a more efficient protection against convulsions elicited by pentetrazol than by picrotoxin. In the case of picrotoxin induced convulsive seizures where there is an alteration at the GABA receptor level, ther is a lack of efficiency after nDPA treatment which increases GABA at the synaptic level. DPA is more effective against pentetrazol convulsive seizures where no direct participation of GABAergic receptors seems to occur. The efficiency of potentialisation of GABAergic mediation is a function of the mechanism by which the seizure is triggered.


Molecular pathogenesis and clinical variability of homozygous beta0-thalassemia in populations of Jammu region of J&K state (India).
This study was undertaken to evaluate the variation in the clinical presentation of homozygous beta0-thalassemia from severe disease to a beta-thalassemia intermedia phenotype and to look for the contribution of associated factors in this variation of clinical course. Type of beta0-thalassemia mutations, associated alpha-thalassemia, and XmnI polymorphism in the gamma globin gene, which are known to affect the clinical course of the disease, were investigated from 15 homozygous beta0-thalassemia patients comprising 11 patients with beta-thalassemia major and 4 patients with beta-thalassemia intermedia. Transfusion dependency and the age at which the patient presented with symptoms were used to assess the degree of clinical severity of these patients. Three different beta0-thalassemia mutations viz. CD 41-42 (-TTCT), CD 8-9 (+G) and 619 bp deletion, were encountered among the 30 beta-thalassemia alleles. It was observed that the type of beta0-thalassemia mutations was not different between the two groups, but co-inheritance of one or more alpha-gene deletions and the presence of the XmnI polymorphism were associated with lesser severity of the disease.


Impact of common contraceptive methods on quality of life and sexual function in Hong Kong Chinese women.
The combined oral contraceptive (COC) pills, injectables, intrauterine contraceptive device (IUCD) and female sterilization are the most common contraceptive methods used by women. Women's choice, compliance and satisfaction with specific contraceptive methods are influenced by any impact of the method on their quality of life and sexual function. Anxiety regarding possible adverse effects of the contraceptive methods on their quality of life and sexual function is one of the common concerns. The aim of this prospective observational study was to determine the impact of the abovementioned contraceptive methods on the quality of life and sexual function of the users. A sample of 361 Hong Kong Chinese women who were first-time users of the following contraceptive methods completed the study: COC pills (n=87), injectables (n=67), IUCD (n=96) and female sterilization (n=111). Quality of life and sexual function of the subjects were assessed before and 3-4 months after use of the method by a standardized questionnaire. The questions were adopted from the validated Chinese versions of the World Health Organization Quality of Life (WHOQOL) questionnaire and the Derogatis Sexual Functioning Inventory (DSFI). In the female sterilization group, we found a significantly higher score for sexual satisfaction (p=.004) and sexual drive (p=.003) 3-4 months after sterilization, as well as an improved WHOQOL social domain score (p=.009). However, the other DSFI subscale scores and WHOQOL domain scores were not significantly different (p>.05). No significant difference was demonstrated in all the WHOQOL domain scores and DSFI subscale scores after use of COC pills, injectables and IUCD (p>.05). We conclude that the COC pills, injectables, IUCD and female sterilization all do not have significant adverse impact on quality of life and sexual function. After female sterilization, there is a significant improvement in sexual satisfaction and sexual drive.


[An in-vitro study of the use of palatal arches in controlling the position of the upper molars].
An in-vitro study was performed analysing the forces and moments produced by the transpalatal arches of the Goshgarian type (0.036" x 0.032" stainless steel and and of the "Precision Lingual Arch System" advocated by Burstone (0.032" x 0.032" stainless steel and 0.032" x 0.032" TMA) using an electronic force-moment gauge recently developed by Planert. The palatal bars were adapted passively, and in addition, molar expansion, symmetrical molar rotation, and buccal root torque were applied. It was found that under clinical conditions it was impossible to fabricate an absolutely passive arch wire with any of the arch types under investigation. The highest precision in applying forces and moments together with the least side-effects was possible using the low stiffness TMA version of the Burstone system.


[A case of testicular torsion in a neonate].
A case of testicular torsion in a neonate is reported. A two-day-old boy with an abnormal hard mass in the right scrotum was referred to us. Right testicular torsion was suspected and operation was performed at 13 days after birth. During the operation extra-vaginal torsion of the right spermatic cord was revealed. The right testis appeared extensively necrotic, and right orchiectomy was selected. Histological examination revealed massively coagulo-necrotic testicular structure. To our knowledge, this is the 56th case of testicular torsion in a neonate reported in Japan. We discussed the onset, laterality, form, direction, angle and treatment of the torsion.


Synthesis of (Z)-trisubstituted olefins by decarboxylative grob-type fragmentations: epothilone D, discodermolide, and peloruside A.
Methyl-branched (Z)-trisubstituted olefins are found in many polyketides with interesting biological activity, such as epothilone D (1), discodermolide (3), and peloruside A (2). Despite the employment of numerous different strategies, this motif has often been the weak point in total synthesis. Thus, we present a novel hydroxide- induced Grob-type fragmentation as an easy access to trisubstituted olefins. In our case, beta-mesyloxy delta-lactones with three stereogenic centers were chosen whose fragmentation underlies a high stereoelectronic control. Major challenges in the syntheses were the installation of quaternary stereocenters, achieved by enzymatic desymmetrization of meso-diesters and by aluminium-promoted stereoselective rearrangement of chiral epoxides, respectively. Different aldol strategies were developed for the formation of the fragmentation precursors. Additionally a short survey about nucleophilic additions to aldehydes with quaternary alpha-centers is presented.


Sialolith removal in the submandibular region using surgical diode laser: report of two cases and literature review.
Sialolithiasis is defined as the presence of one or more calcified structures within the duct of a major or minor salivary gland. It occurs as a result of deposition of calcium salts around an accumulation of organic debris in the duct lumen. The main signs and symptoms are edema and bacterial infection with abscess formation. This study aimed to report two cases of submandibular sialolithiasis treated surgically with diode laser and conduct a review of the literature by means of a systematic search. In the two cases, the calculi were located in the distal part of the submandibular duct and could be palpated intraorally. Surgery was performed in an outpatient setting under local anesthesia. A linear incision was made in the floor of the mouth, in the region of the opening of Wharton's duct, to expose and remove the calculi. Laser cutting was performed using a diode laser module coupled to a 400-μm optical fiber emitting at a wavelength of 980 nm (infrared), 2.5 W output power, and in continuous pulse mode. The use of diode laser is a safe and minimally invasive option for this type of procedure. Offering advantages such as enhanced coagulation properties and high-quality incision, absence of bleeding, low risk of nerve damage, and few comorbidities.


Nonpeptic ulcer, nonvariceal gastrointestinal bleeding in hemodialysis patients.
Hemodialysis patients carry a higher risk of peptic ulcer bleeding. Whether hemodialysis patients also have a higher occurrence of nonpeptic ulcer, nonvariceal gastrointestinal bleeding needs further evaluation. Using Taiwan's National Health Insurance research database, the occurrence of nonpeptic ulcer, nonvariceal gastrointestinal bleeding was compared among the hemodialysis patients, chronic kidney disease patients, and controls using log-rank test. Risk factors were identified by Cox regression analysis. A total of 20,830 patients were enrolled, including 8210 hemodialysis and 4190 chronic kidney disease patients and 8430 age- and sex-matched controls in a 2:1:2 ratio. In the 7-year follow-up period, hemodialysis patients had a significantly higher cumulative hazard of nonpeptic ulcer, nonvariceal gastrointestinal bleeding than chronic kidney disease patients and controls (P <.001, by log-rank test). The hazard also was significantly higher in the chronic kidney disease patients than in controls. Cox regression analysis revealed that older age, the comorbidities of diabetes mellitus, cirrhosis, and chronic obstructive pulmonary disease, history of uncomplicated peptic ulcer disease, chronic kidney disease (hazard ratio 5.17), hemodialysis (hazard ratio 9.43), and use of selective serotonin reuptake inhibitors were independent risk factors for nonpeptic ulcer, nonvariceal gastrointestinal bleeding in all study patients. Old age, diabetes mellitus, cirrhosis, chronic obstructive pulmonary disease, history of uncomplicated peptic ulcer disease, and use of selective serotonin reuptake inhibitors were independent risk factors in hemodialysis patients. There is a higher risk of developing nonpeptic ulcer, nonvariceal gastrointestinal bleeding in hemodialysis patients after adjustments for age, sex, underlying comorbidities, and ulcerogenic medication. The risk has increased since patients had chronic kidney disease.


NK1 receptor-mediated endothelium-dependent relaxation and contraction with different sensitivity to post-receptor signaling in pulmonary arteries.
In rabbit intrapulmonary arteries, substance P (SP) has been reported to induce endothelium-dependent relaxation (EDR) and endothelium-dependent contraction (EDC) via tachykinin NK(1) receptors, and endothelium-independent contraction (EIC) via tachykinin NK(2) receptors. The present study pharmacologically examined whether these opposite responses (EDR and EDC) are mediated by the same NK(1) receptor. Five tachykinin agonists, including septide, a reportedly atypical NK(1) agonist, caused concentration-dependent EDR in the presence of NK2 antagonist (SR-48968) + TXA2 synthetase inhibitor (ozagrel), which blocked EIC and EDC, in pre-contracted arteries, and concentration-dependent EDC in the presence of NK2 antagonist (SR-48968) + nitric oxide synthase inhibitor (l-N(G)-nitro-arginine methyl ester), which blocked EIC and EDR, in non-contracted arteries. The EC(50) values of these agonists for EDR were smaller than those for EDC, indicating that the affinities of NK(1) agonists to NK(1) receptors are different between EDR and EDC. However, the rank order of their potency for EDR and EDC was the same: SP = septide > SP methyl ester (SPME) > neurokinin A > neurokinin B. [Ala(5), beta-Ala(8)]-alpha-neurokinin fragment 4-10 (NK2 agonist) and senktide (NK3 agonist) caused no responses. Two structurally different NK(1) antagonists, CP-99994 and SR-140333, shifted the concentration-EDC and -EDR curves of SPME, a selective NK(1) agonist, and septide rightward and suppressed their maximal responses in a similar concentration-dependent manner, indicating that the affinities of NK(1) antagonists to NK1 receptors are similar between EDR and EDC. U-73122, a phospholipase C inhibitor, and thapsigargin, 2,5-di-tert-butylhydroquinone, and ruthenium red, all intracellular Ca2+ release blockers, inhibited SP-induced EDR and EDC. Effective concentrations of ionomycin (Ca2+ ionophore) causing EDR were also lower than those causing EDC. Taken together, SP-induced EDR and EDC are mediated by activation of the same NK1 receptor followed by an increase in intracellular Ca2+, and sensitivity to Ca2+ may be higher in the EDR than EDC pathway.


Characterization of the periplasmic heme-binding protein shut from the heme uptake system of Shigella dysenteriae.
The heme uptake systems by which bacterial pathogens acquire and utilize heme have recently been described. Such systems may utilize heme directly from the host's hemeproteins or via a hemophore that sequesters and transports heme to an outer membrane receptor and subsequently to the translocating proteins by which heme is further transported into the cell. However, little is known of the heme binding and release mechanisms that facilitate the uptake of heme into the pathogenic organism. As a first step toward elucidating the molecular level events that drive heme binding and release, we have undertaken a spectroscopic and mutational study of the first purified periplasmic heme-binding protein (PBP), ShuT from Shigella dysenteriae. On the basis of sequence identity, the ShuT protein is most closely related to the class of PBPs typified by the vitamin B(12) (BtuF) and iron-hydroxamate (FhuD) PBPs and is a monomeric protein having a molecular mass of 28.5 kDa following proteolytic processing of the periplasmic signaling peptide. ShuT binds one b-type heme per monomer with high affinity and bears no significant homology with other known heme proteins. The resonance Raman, MCD, and UV-visible spectra of WT heme-ShuT are consistent with a five-coordinate high spin heme having an anionic O-bound proximal ligand. Site-directed ShuT mutants of the absolutely conserved Tyr residues, Tyr-94 (Y94A) and Tyr-228 (Y228F), which are found in all putative periplasmic heme-binding proteins, were subjected to UV-visible, resonance Raman, and MCD spectroscopic investigations of heme coordination environment and rates of heme release. The results of these experiments confirmed Tyr-94 as the only axial heme ligand and Tyr-228 as making a significant contribution to the stability of heme-loaded ShuT, albeit without directly interacting with the heme iron.


Production and Analysis of Conditional KO Mice of CCN2 in Kidney.
CCN2 has been shown to be closely involved in the progression of renal fibrosis, indicating the potential of CCN2 inhibition as a therapeutic target. Although the examination of the phenotypes of adult CCN2 knockout mice with renal diseases has yielded valuable scientific insights, perinatal death has limited studies of CCN2 in vivo. Conditional knockout technology has become widely used for the deletion of genes in the desired cell populations and time points through the use of cell-specific Cre recombinase-expressing mice. Accordingly, several lines of CCN2 floxed mice have been developed for the assessment of the functional role of CCN2 in adult mice.CCN2 levels are increased in renal fibrosis and proliferative glomerulonephritis, which represent good disease models for evaluating the effects of CCN2 deletion on the kidney. Of these, anti-glomerular basement membrane antibody glomerulonephritis has become the most widely used model for evaluating the effect of increased renal CCN2 expression. Herein, we describe the construction of CCN2 floxed mice and inducible systemic CCN2 conditional knockout mice and methods for the induction of anti-glomerular basement membrane antibody glomerulonephritis.


Enamel erosion and mechanical tooth wear in medieval Icelanders.
The Icelandic Sagas are an important source of information on the way of life and diet habits in Iceland and possibly other Nordic countries 1000 years ago. Archaeological human skull material worldwide has revealed extensive tooth wear, with the main cause believed to be coarse diet. From a graveyard near volcano Hekla, 66 skeletons dated from before 1104 were excavated. The purpose of this study was to determine the main causes of tooth wear in Icelanders 1000 years ago. Forty-nine skulls were available for research. Two methods were used to evaluate tooth wear and seven for age estimation. An attempt was made to determine the main causes of tooth wear in the light of likely diet and beverage consumption according to a computer search on food and drink customs described in the Icelandic Sagas. Tooth wear was extensive in all groups, increasing with age. The highest score was on first molars, with no difference between sexes. It had all the similarities seen in wear from coarse diet. In some instances it had similar characteristics to those seen in erosion in modern Icelanders consuming excessive amounts of soft drinks. According to the Sagas, acidic whey was a daily drink and used for preservation of food in Iceland until recently. Since acidic whey has considerably high dental erosive potential, it is postulated that consumption of acidic drinks and food, in addition to a coarse and rough diet, played a significant role in the dental wear of ancient Icelanders.


Two-incision THA had modest outcomes and some substantial complications.
Proponents of two-incision total hip arthroplasty suggest the technique is minimally invasive and promotes rapid rehabilitation with a low prevalence of complications. We applied the two-incision total hip arthroplasty technique to a consecutive group of unselected patients with primary degenerative arthritis to determine the technical difficulty of the operation as measured by the operative time compared with a standard posterior approach, the safety of the operation as measured by the prevalence of complications compared with a standard posterior approach, and the early functional outcome measured by the time to return to activities of daily living as compared with a previous study of the two-incision technique in selected younger patients. The 80 patients included 45 women and 35 men with a mean age of 70.5 years. The patients treated with a two-incision method had longer operative times and substantially more complications than did the patients treated with a standard posterior approach. The early functional outcomes in this group of unselected patients were modest when compared with the previous results in selected younger patients. Patient and surgeon enthusiasm for the potential benefits of the two-incision total hip arthroplasty should be tempered by the modest early outcomes and the substantial prevalence of complications found in this group of typical patients having total hip arthroplasty. Prognostic study, Level III (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence.


Transcription in the archaea: basal factors, regulation, and stress-gene expression.
A brief survey is presented of salient findings on transcription in the Archaea, focussing on stress genes of the hsp70(dnaK locus, which code for the molecular chaperones Hsp70(DnaK), Hsp40(DnaJ), and GrpE. Archaeal basal factors and some recently characterized regulators pertinent to non-stress genes are presented first to show their similarities and differences with equivalents in organisms of the other two phylogenetic domains, Bacteria and Eucarya, and to reveal clues on how these or similar factors might transcribe and regulate the archaeal stress genes. The second part of the article deals with the hsp70(dnaK)-locus genes, particularly those from Methanosarcina mazeii, because they are virtually the only ones within the methanogenic Archaea whose patterns of constitutive and stress-induced expressions have been studied. Therefore, these genes provide a standardized model system to elucidate transcription initiation and regulation at the molecular level in this phylogenetic group. Promoters, and other cis-acting sites that are, or might be, involved in stress-gene expression are described. Conformational changes of basal transcription factors after interaction with stress-gene promoters are discussed that suggest ways for generating a large diversity of initiation complexes using a few factors and DNA sites in different combinations. Likewise, the effects of stress on DNA topology and on TBP-TFB-promoter complex formation and tightness are described, which might also contribute to the generation of transcription-initiation complex diversity. This diversity would be key to differential gene expression, namely, which genes are transcribed, when (basal, steady expression vs. sporadic stress-induced expression), and to what level. Future research should investigate this diversity, and the mechanism of complex formation and action at the atomic, molecular, and supramolecular levels, to elucidate the dynamics of transcription initiation in real time.


Classroom Enters the Courtroom: Stereochemistry of SN1 and SN2 Reactions in Enantiomer Patent Litigations of the Antidepressant Escitalopram.
The role of elementary stereochemistry is illustrated in the patent litigations of the blockbuster antidepressant drug escitalopram oxalate. An undergraduate student of organic chemistry would recognize the stereochemical courses of the intramolecular SN 2 and SN 1 reactions of the single-enantiomer (S)-diol intermediate in the synthesis of the blockbuster antidepressant drug escitalopram oxalate: retention of configuration of the chiral carbon atom under basic conditions and racemization under acidic conditions, respectively. He/she, in searching for a stereoselective ring-closure reaction of the enantiomeric diol, will think of an SN 2 reaction in a basic medium. From these points of view, the process claim in the enantiomer patents of escitalopram is obvious/lacks an inventive step. An organic chemistry examination problem based on this scenario is offered.


Are complications in intraoperative radiation therapy more frequent than in conventional treatment?
To evaluate whether intraoperative radiation therapy (IORT) results in higher complication rates than conventional radiotherapy, 119 patients were studied who entered four prospectively randomized clinical trials that compared IORT with conventional therapy. Malignant neoplasms included 33 gastric carcinomas, 35 retroperitoneal sarcomas, 22 resectable pancreatic cancers, and 29 unresectable pancreatic cancers. One hundred thirty-six complications developed among 66 patients who received conventional therapy, and 108 complications developed among 53 patients who received IORT. There was no statistical significance between treatment groups with respect to the overall incidence of complications. Analysis of types of complications by tumor type using Fisher's exact test revealed only one significant complication: an increased rate of sepsis among the patients with retroperitoneal sarcoma who received conventional therapy compared with their IORT cohorts. The overall complication rate associated with IORT was equivalent to conventional radiotherapy in the treatment of these malignant neoplasms and supported the use of IORT where clinically indicated.


[Case-control study on effects of vacuum drainage on perioperative blood loss after total hip arthroplasty for the treatment of femoral neck fractures].
To compare postoperative blood loss under different negative pressures of drainage after total hip arthroplasty for the treatment of femoral neck fractures. From January 1st to December 30th 2013, 74 patients with femoral neck fractures treated with total hip arthroplasty were randomly divided into two groups: high negative pressure drainage group and low negative pressure drainage group. In high negative pressure drainage group, there were 34 cases including 10 males and 24 females, with a mean age of (75.94 ± 9.02) years old, and the patients were treated with 60 kPa negative pressure of drainage. In the low negative pressure drainage group, there were 40 cases including 13 males and 27 females, with an average age of (74.93 ± 8.90) years old, and the patients were treated with 30 kPa negative pressure of drainage. The amount of total drainage, total blood loss, and hemoglobin change were compared between these two groups. All the patients got primary healing without infections. In high negative pressure drainage group,the change of hemoglobin was (41.74 ± 15.69) g/L, total blood loss was (1,217.73 ± 459.50) ml and the drainage volume was (312.94 ± 103.44) ml; while in low negative pressure drainage group,the results were (34.90 ± 12.90) g/L, (904.01 ± 381.58) ml and (129.25 ± 44.25) ml separately. All the results in high negative pressure drainage group were higher than those in the other group. Three days after operation, the change of hemoglobin was (46.00 ± 13.29) g/L and total blood loss was (1,304.72 ± 421.75) ml; while in low negative pressure drainage group, the changes of hemoglobin was (43.87 ± 11.39) g/L and total blood loss was (1,196.78 ± 344.20) ml; there were no statistically significant differences between two groups. When placing drainage devices after total hip arthroplasty for the treatment of femoral neck fractures, the level of negative pressure should be chosen according to preoperative level of hemoglobin and HCT in patients. For old patients with femoral neck fracture, low negative pressure is more suitable.


Characterization of epiphycan, a small proteoglycan with a leucine-rich repeat core protein.
The epiphysis of developing bones is a cartilaginous structure that is eventually replaced by bone during skeletal maturation. We have separated a dermatan sulfate proteoglycan, epiphycan, from decorin and biglycan by using dissociative extraction of bovine fetal epiphyseal cartilage, followed by sequential ion-exchange, gel permeation, hydrophobic, and Zn2+ chelate chromatographic steps. Epiphycan is a member of the small leucine-rich proteoglycan family, contains seven leucine-rich repeats (LRRs), is related to osteoglycin (osteoinductive factor) (Bentz, H., Nathan, R. M., Rosen, D. M., Armstrong, R. M., Thompson, A. Y., Segarini, P. R., Mathews, M. C., Dasch, J., Piez, K. A., and Seyedin, S. M. (1989) J. Biol. Chem. 264, 20805-20810), and appears to be the bovine equivalent of the chick proteoglycan PG-Lb (Shinomura, T., and Kimata, K. (1992) J. Biol. Chem. 267, 1265-1270). The intact proteoglycan had a median size of approximately 133 kDa. The core protein was 46 kDa by electrophoretic analysis, had a calculated size of 34,271 Da, and had two approximately equimolar N termini (APTLES ... and ETYDAT ... ) separated by 11 amino acids. There were at least three O-linked oligosaccharides in the N-terminal region of the protein, based on blank cycles in Edman degradation and corresponding serine or threonine residues in the translated cDNA sequence. The glycosaminoglycans ranged in size from 23 to 34 kDa were more heterogeneous than those in other dermatan sulfate small leucine-rich proteoglycans and were found in the acidic N-terminal region of the protein core, N-terminal to the LRRs. A four-cysteine cluster was present at the N terminus of the LRRs, and a disulfide-bonded cysteine pair was present at the C terminus of the protein core. The seventh LRR and an N-linked oligosaccharide were between the two C-terminal cysteines. An additional potential N-glycosylation site near the C terminus did not appear to be substituted at a significant level.


Outcome of Frail Do-Not-Intubate Subjects With End-Stage Chronic Respiratory Failure and Their Opinion of Noninvasive Ventilation to Reverse Hypercapnic Coma.
The use of noninvasive ventilation (NIV) in the emergency setting to reverse hypercapnic coma in frail patients with end-stage chronic respiratory failure and do-not-intubate orders remains a questionable issue given the poor outcome of this vulnerable population. We aimed to answer this issue by assessing not only subjects' outcome with NIV but also subjects' point of view regarding NIV for this indication. A prospective observational case-control study was conducted in 3 French tertiary care hospitals during a 2-y period. Forty-three individuals who were comatose (with pH < 7.25 and PaCO2 > 100 mm Hg at admission) were compared with 43 subjects who were not comatose and who were treated with NIV for acute hypercapnic respiratory failure. NIV was applied by using the same protocol in both groups. They all had a do-not-intubate order and were considered vulnerable individuals with end-stage chronic respiratory failure according to well-validated scores. NIV yielded similar outcomes in the 2 groups regarding in-hospital mortality (n = 12 [28%] vs n = 12 [28%] in the noncomatose controls, P > .99) and 6-month survival (n = 28 [65%] vs n = 22 [51%] in the noncomatose controls, P = .31). Despite poor quality of life scores (21.5 ± 10 vs 31 ± 6 in the awakened controls, P = .056) as assessed by using the VQ11 questionnaire 6 months to 1 y after hospital discharge, a large majority of the survivors (n = 23 [85%]) would be willing to receive NIV again if a new episode of acute hypercapnic respiratory failure occurs. In the frailest subjects with supposed end-stage chronic respiratory failure that justifies treatment limitation decisions, it is worth trying NIV when acute hypercapnic respiratory failure occurs, even in the case of extreme respiratory acidosis with hypercapnic coma at admission.


Triploidy after in vitro fertilization: cytogenetic analysis of human zygotes and embryos.
Tripronuclear zygotes obtained from a clinical IVF program were studied cytogenetically. Successful analysis was possible of 42 specimens at the zygote stage and 21 embryos after the first or second cleavage division. In the majority of zygotes (88%) the expected triploidy was confirmed, whereas only 14% of embryos had solely triploid cells. Therefore it is concluded that after tripolar cleavage division, many different types of mosaicism may originate from irregular chromosome distributions. Since the findings in individual blastomeres in embryos resulting from multipronuclear zygotes do not reflect the genetic content of the whole embryo, these embryos are less suitable in a model system for preimplantion diagnosis. The distribution of the sex chromosomal types (XXX, XXY, and XYY) confirmed theoretical expectations. Since in abortion material or in liveborn triploidy cases, the XYY karyotype is hardly ever observed, this indicates that most likely the 69,XYY karyotype has a very high embryonic mortality.


Fetal glucocorticoid-regulated pathways are not affected by inhaled corticosteroid use for asthma during pregnancy.
Inhaled corticosteroids (ICS) are currently advised for the control of asthma during pregnancy, despite the lack of evidence regarding potential systemic effects on maternal, placental, and fetal systems. To determine maternal plasma concentrations of cortisol, estriol, osteocalcin, and corticotropin-releasing hormone in pregnant women with asthma (n = 156) and without asthma (n = 51). During each trimester of pregnancy, the use and dose of ICS was recorded and blood samples were collected. Ultrasound was performed at 18 and 30 weeks' gestation, and birth weight and fetal sex were recorded at delivery. Maternal hormone concentrations were not affected by the presence of asthma; however, they were inhibited by ICS use in a dose-dependent manner. This was dependent on fetal sex: in pregnancies with a female, ICS was inversely associated with maternal cortisol in first trimester and inversely associated with maternal osteocalcin in second and third trimester. When pregnant with a male, no effect of ICS dose was observed on maternal cortisol, estriol, or osteocalcin levels, whereas corticotropin-releasing hormone levels were increased with ICS use only in the first trimester. Maternal glucocorticoid-regulated systems appeared susceptible to ICS only when pregnant with a female. Fetal adrenal function appeared unaffected by ICS in pregnancies of both males and females. This provides clinically important information suggesting that ICS do not exert effects on glucocorticoid-regulated pathways in the fetus, and therefore are unlikely to contribute to adverse effects on fetal growth and development.


Chemoprevention of lung pathologies by dietary n-3 polyunsaturated fatty acids.
Different intervention trials have been so far conducted and others are ongoing to evaluate the effect of increased intake of n-3 polyunsaturated fatty acids (PUFAs) in the prevention of several disorders affecting lungs and airways. They have been focused on chronic obstructive pulmonary disease, acute respiratory distress syndrome, acute lung injury, pulmonary fibrosis, alteration of lung function in cystic fibrosis, as well as asthma and cachexia in lung cancer patients. Their outcomes are not always consistent, but, if beneficial effects were observed, they have been related mainly to the anti-inflammatory action of n-3 PUFAs. On the contrary, trials investigating their effects on the development and progression of lung cancer are still not available. This in spite of the huge number of equivalent studies performed on other kind of cancers (breast, colon and prostate cancer), which share with lung cancer the highest incidence in Western countries and an elevated sensitivity to chemoprevention. Contrasting results were also obtained by the few epidemiological studies available on lung cancer. However, different experimental studies, performed in vivo and in vitro, provided strong indications of the anti-tumor action of n-3 PUFAs against lung cancer, and identified molecular mechanisms for their action. In this review our effort will concentrate in critically reviewing the current evidence for the beneficial effect of n-3 PUFAs in inflammatory and neoplastic disorders of lungs and airways, and in identifying possible molecular mechanisms underlying their effects.


Metabolites of arsenic and increased DNA damage of p53 gene in arsenic plant workers.
Recent studies have shown that monomethylarsonous acid is more cytotoxic and genotoxic than arsenate and arsenite, which may attribute to the increased levels of reactive oxygen species. In this study, we used hydride generation-atomic absorption spectrometry to determine three arsenic species in urine of workers who had been working in arsenic plants,and calculated primary and secondary methylation indexes. The damages of exon 5, 6, 8 of p53 gene were determined by the method developed by Sikorsky, et al. Results show that the concentrations of each urinary arsenic species,and damage indexes of exon 5 and 8 of p53 gene in the exposed population were significantly higher, but SMI was significantly lower than in the control group. The closely positive correlation between the damage index of exon 5 and PMI,MMA, DMA were found, but there was closely negative correlation between the damage index of exon 5 and SMI. Those findings suggested that DNA damage of exon 5 and 8 of p53 gene existed in the population occupationally exposed to arsenic. For exon 5, the important factors may include the model of arsenic metabolic transformation, the concentrations of MMA and DMA, and the MMA may be of great importance.


Effect of iron supplementation on the expression of hypoxia-inducible factor and antioxidant status in rats exposed to high-altitude hypoxia environment.
Iron and oxygen are essential substance for cellular activity in body tissues. Hypoxia-inducible factors (HIFs) can respond to available oxygen changes in the cellular environment and regulate the transcription of a series of target genes. The study was conducted to investigate the effects of iron supplementation on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and antioxidant status in rats exposed to high-altitude hypoxia environment. Forty rats were divided into control (CON), hypobaric hypoxia (HH), and hypobaric hypoxia plus ferrous sulfate (FeSO4) (9.93 mg/kg body weight (BW)/day) (HFS) and hypobaric hypoxia plus iron glycinate chelate (Fe-Gly) (11.76 mg/kg BW/day) (HFG) groups. Results showed that Fe-Gly effectively alleviated weight loss and intestinal mucosa damage induced by hypobaric hypoxia, whereas FeSO4 aggravated hypobaric hypoxia-induced weight loss, liver enlargement, spleen atrophy, and intestinal damage. Iron supplementation decreased liver superoxide dismutase (T-SOD) and catalase (CAT) activity (P < 0.01) and increased iron concentration in the liver compared to HH group (P < 0.001). Moreover, Fe-Gly upregulated liver transferrin expression in messenger RNA (mRNA) level (P < 0.05) and downregulated serum erythropoietin (EPO) concentration (P < 0.01) and liver HIF-1α expression level (P < 0.05 in mRNA level; P < 0.001 in protein level) compared to HH group. The study indicated that FeSO4 supplementation at high altitudes aggravated the oxidative damage of tissues and organs that could be mediated through production of malondialdehyde (MDA) and inhibition antioxidant enzyme activities. Fe-Gly can protect hypobaric hypoxia-induced tissues injury. Moreover, iron supplementation at high altitudes affected HIF-1α-mediated regulating expression of targeting genes such as EPO and transferrin. The study highlights that iron supplementation under hypobaric hypoxia environment has possible limitation, and efficient supplementation form and dosage need careful consideration.


End-to-End versus End-to-Side Microvascular Anastomosis: A Meta-analysis of Free Flap Outcomes.
Background Optimal outcomes in microsurgery have been attributed to a range of factors, with performing of end-to-end (ETE) versus end-to-side (ETS) influencing anastomotic complications and flap outcomes. Methods A systematic review of the literature and meta-analysis was undertaken to evaluate the relative risks of anastomotic complications with ETE versus ETS approaches, for arterial and venous anastomoses looking at risk ratios (RRs) for thrombosis and overall flap failure. Results RRs of thrombosis and flap failure in ETS versus ETE venous anastomosis groups were 1.30 (95% confidence interval [CI]: 0.53-3.21) and 1.50 (95% CI: 0.85-2.67), respectively. The RRs of thrombosis and flap failure in ETS versus ETE arterial anastomosis groups were 1.04 (95% CI: 0.32-3.35) and 1.04 (95% CI: 0.72-1.48), respectively. Conclusion Differences in rates of thrombosis and flap failure between ETE and ETS venous and arterial anastomoses are marginal and nonsignificant. As such, the type of anastomotic technique is best decided on a case-by-case basis, dependent on anatomical, surgical, and patient factors.


Heavy metals, islet function and diabetes development.
It has long been believed that heavy metals possess many adverse health effects. Uncontrolled industrialization has released heavy metal pollution in the world. Heavy metal pollutants damage organ functions and disrupt physiological homeostasis. Diabetes mellitus is growing in prevalence worldwide. Several studies have indicated that the deficiency and efficiency of some essential trace metals may play a role in the islet function and development of diabetes mellitus. Some toxic metals have also been shown to be elevated in biological samples of diabetes mellitus patients. In the present work, we review the important roles of heavy metals in islet function and diabetes development in which the in vitro, in vivo or human evidences are associated with exposure to zinc, arsenic, cadmium, mercury and nickel. Through this work, we summarize the evidence which suggests that some heavy metals may play an important role in diabetes mellitus as environmental risk factors.


[Problems during the curing of complete dentures].
In this article, there are described within the limitations of the given space, the problems arising during the procedure of curing of complete dentures as well as the methods available for overcoming these problems is a satisfactory way. Overcoming these problems would have a positive result on delivering from the flasks dentures which will dispose bases which such mechanical abilities sufficiently capable to resist in the mechanical stresses, during the function of chewing.


Quantitative estimates of vascularity in a collagen-based cell scaffold containing basic fibroblast growth factor by noninvasive near-infrared spectroscopy for regenerative medicine.
Successful tissue regeneration requires cells with high proliferative and differentiation potentials as well as an environment that promotes regeneration. Since cell scaffolds and growth factors provide such an environment and also induce angiogenesis and cell proliferation, we examined the hemoglobin content of implanted collagen-based cell scaffolds containing the angiogenic factor, basic fibroblast growth factor (bFGF), in vivo with noninvasive near infrared spectroscopy (NIRS). Angiogenesis within cell scaffolds is typically determined by histological examination for endothelial cell markers. Unfortunately, this approach requires removal of tissue and scaffold invasively. We compared the hemoglobin content of implanted collagen-based cell scaffold as measured by NIRS to the hemoglobin content measured with a conventional invasive hemoglobin assay. Noninvasive NIRS recordings were performed with a custom-built near-infrared spectrometer using light guide-coupled reflectance measurements. NIRS recordings revealed that absorbance increased after implantation of collagen scaffolds containing bFGF. This result correlated (R2 = 0.93) with a subsequent conventional hemoglobin assay. The NIRS technique provides a noninvasive method for measuring the degree of vascularization in cell scaffolds. This technique may be advantageous for monitoring angiogenesis within different cell scaffolds, a prerequisite for effective tissue regeneration.


Coordination of Morphogenesis and Cell-Fate Specification in Development.
During animal development, cell-fate-specific changes in gene expression can modify the material properties of a tissue and drive tissue morphogenesis. While mechanistic insights into the genetic control of tissue-shaping events are beginning to emerge, how tissue morphogenesis and mechanics can reciprocally impact cell-fate specification remains relatively unexplored. Here we review recent findings reporting how multicellular morphogenetic events and their underlying mechanical forces can feed back into gene regulatory pathways to specify cell fate. We further discuss emerging techniques that allow for the direct measurement and manipulation of mechanical signals in vivo, offering unprecedented access to study mechanotransduction during development. Examination of the mechanical control of cell fate during tissue morphogenesis will pave the way to an integrated understanding of the design principles that underlie robust tissue patterning in embryonic development.


Directly observed therapy of tuberculosis in Brazil: associated determinants and impact on treatment outcome.
All Brazilian states. To assess the determinants of tuberculosis (TB) in patients undergoing directly observed therapy (DOT) and the impact of DOT on treatment outcomes. This is a cross-sectional study among TB patients aged ⩾18 years conducted in 2011. The primary outcome was the status of DOT received, while the secondary was the outcome of anti-tuberculosis treatment. In 2011, 35 775 (38.3%) subjects received DOT. The odds of receiving DOT were higher in patients with the following characteristics: brown/mestizo patients (OR 1.18, 95%CI 1.14-1.22) and those of other ethnic groups (OR 2.01, 95%CI 1.79-2.27) compared to Whites, alcohol users (OR 1.37, 95%CI 1.28-1.47) and those with mental disorders (OR 1.88, 95%CI 1.54-2.29). The odds of receiving DOT were lower in human immunodeficiency virus positive patients (OR 0.64, 95%CI 0.60-0.68). Patients who did not receive DOT were more likely to default from anti-tuberculosis treatment (OR 0.62, 95%CI 0.57-0.66), die due to TB (OR 0.68, 95%CI 0.61-0.77) and to have unknown treatment outcomes (OR 0.71, 95%CI 0.66-0.76). The adjusted preventable fraction of DOT in the reduction of unfavorable outcomes was 25%. Sociodemographic and clinical characteristics are determinants of anti-tuberculosis treatment outcomes in patients undergoing DOT; DOT use led to a 25% reduction in unfavorable outcomes.


Contemporary Drug-Eluting Stent Platforms: Design, Safety, and Clinical Efficacy.
First-generation drug-eluting stents significantly improved treatment of coronary disease, decreasing rates of revascularization. This was offset by high rates of late adverse events, driven primarily by stent thrombosis. Research and design improvements of individual DES platform components led to next-generation devices with superior clinical safety and efficacy profiles compared with bare-metal stents and first-generation drug-eluting stents. These design improvements and features are explored, and their resulting clinical safety and efficacy reviewed, focusing on platforms approved by the Food and Drug Administration currently widely used in the United States.


[Evaluation of abiotic ecological factors and their dynamics at various densities in raising broilers].
Three productional experiments were carried out in which the broilers were kept on unified premises under one and the same technology, but at various densities of raising: 14.4 and 23.4/sq. m., and 16.6 and 23.6/sq. m. with the second and third experiment. The dynamic, light intensity, and content of toxic gases along with the homogenization of air in the birds' vital zone were followed up. Differences were established which were defined by the higher density of raising, and which, acting as a constellation on the organism might lower the effectiveness of the technologies employed.


[Visual evoked functional connectivity before and after smoking cessation based on functional magnetic resonance imaging].
To explore differences in visual information processing for smoking addicts between before and after smoking cessation based on functional magnetic resonance imaging technology. Methods: Seventeen volunteers, with heavy dependence on nicotine, agreed to give up smoking and to complete the test. The primary visual network and secondary visual network were extracted by independent component analysis technology. The region of interest was defined as the region with significant difference between before and after smoking cessation. The functional connectivity analysis was carried out based on the selected region of interest. Results: After the subjects quitting smoking for 14 days, the increased functional connectivity was observed not only within secondary visual network but also between 2 interested networks; however, no functional connectivity was changed within primary visual network. Conclusion: The ability of visual information processing for smoking addicts could be significantly enhanced after 14 days of smoking cessation.


[Characteristics of two thiol proteinases from spleen active in neutral media].
Two SH-dependent proteinases (I and II) active in neutral media were isolated from bovine spleen and purified to apparent homogeneity. The histone-hydrolyzing activity of proteinase I was increased 3500-fold as compared to that of the original extract. Proteinase I hydrolyzed a variety of proteins (histones, azocasein, hemoglobin, collagen) but did not hydrolyze low molecular weight synthetic substrates, such as BAPA, BANA, BAEE, ATEE, Leu-beta-NA, Arg-beta-Na and Ala-beta-NA. The molecular weight of the enzyme as determined by SDS electrophoresis was found to be about 23,000. Isoelectrofocusing of the enzyme resulted in one major component with pI of 6.05 and in two minor components with pI of 6.2 and 6.4. Proteinase II hydrolyzed Leu-beta-NA, Arg-beta-NA and Ala-beta-NA but did not hydrolyze beta-naphthylamides of dicarboxylic acids and Gly-Phe-beta-Na. This proteinase split BANA and histone and very slowly split azocasein and collagen. Proteinase II was found to have a molecular weight of 30 000 and a pI of 6.8-6.9. Proteinase I inactivated fructose-1.6-diphosphate aldolase, partly inactivated glucose-6-phosphatase dehydrogenase and caused activation of phosphodiesterase of cyclic nucleotides. Proteinase II had no effect on the activity of the above enzymes. A comparison of proteinase I and II with enzymes described in literature demonstrated that the former was cathepsin L, while the latter was cathepsin H from spleen.


EGFR status and KRAS/BRAF mutations in intestinal-type sinonasal adenocarcinomas.
Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumour that is etiologically related to professional exposure to wood dust and exhibits a poor prognosis. Treatment alternatives to surgery and radiotherapy are needed and may be found in anti-EGFR agents. EGFR gene copy number gains and KRAS/BRAF mutations have been reported to act as positive and negative predictors, respectively, of therapeutic response to EGFR targeted therapies in colorectal adenocarcinoma, a tumour type claimed to be genetically similar to ITAC. Therefore, the aim of this study was to evaluate the occurrence and consequence of EGFR alterations and KRAS and BRAF mutations in a large series of ITAC. EGFR protein expression was studied in 98 paraffin embedded tissue samples, organized in a tissue microarray. Gene copy number analysis was performed by FISH using the same tissue microarray, complemented by microarray CGH and MLPA analysis on DNA extracted from 65 fresh frozen tissues. Mutations in EGFR, KRAS and BRAF were analysed by direct sequencing on 65 fresh frozen tissues. EGFR gene copy number gains were observed in 45 %, and protein over-expression in 21 % of the cases. No mutations were found in EGFR or BRAF, while KRAS mutations were present in 12 % of the cases. Neither protein overexpression nor gene copy number gain correlated to histological subtype, tumour stage or clinical follow-up. In the largest series of ITAC published to date, and using a number of different techniques, EGFR alterations were frequently observed. Although apparently not useful as a prognostic factor, there may be a basis for investigating EGFR targeted therapies in this group of patients, especially because negative response predictors such as KRAS and BRAF mutations are infrequent or absent, respectively.


Adsorption characteristics of human plasma fibronectin in relationship to cell adhesion.
Adsorption of human plasma fibronectin (FN) on nonsulfonated and sulfonated polymer surfaces was studied, by using a polyclonal antiserum to FN and the ELISA method. ELISA signal was recorded as a function of FN concentration in solutions. The concentration dependence of FN binding shows the saturation effect in the range 5-10 microg/mL. ELISA data are discussed in the terms of a self-assembled monolayer and different conformations of the FN molecule. The early adhesion of L1210 cells to polymer surfaces after prior adsorption of FN on these surfaces was studied under static conditions. In the case of FN adsorbed on sulfonated surfaces, the relative number of adhering cells increased with the increase of the interfacial surface tension (i.e., the cell adhesion depends on the surface density of sulfonic groups). However, in the case of FN adsorbed on nonsulfonated surfaces, the relative number of adhering cells was low and independent on the interfacial surface tension. The alpha(5)beta(1)-integrin blocking by a monoclonal antibody resulted in a strong inhibition of the cell adhesion to FN adsorbed on sulfonated polymer surfaces. This indicates that cell adhesion to FN adsorbed on these surfaces is mostly mediated by the alpha(5)beta(1)-integrin. In contrast, in the case of FN adsorbed on nonsulfonated surfaces the cell adhesion was not inhibited by the alpha(5)beta(1)-integrin blocking.


Protective effect of SPR-901 (RBS) on the decrease of peripheral leukocyte number in 5-fluorouracil-treated mice.
5-Fluorouracil (5-FU) induces a decrease in the number of peripheral leukocytes (leukopenia), which is one of the major obstacles in the chemotherapy of cancer. The number of peripheral leukocytes decreased by day 4 in mice injected i.p. with 130 mg/kg of 5-FU and recovered to the normal level by day 8. Such a decrease by 5-FU was prevented to some extent by the oral administration of 30 mg/kg/day of SPR-901. Proliferative responses of bone marrow cells to granulocyte/macrophage colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor (G-CSF) were suppressed by 5-FU treatment and their recoveries were enhanced by SPR-901. The serum level of IL-6 in 5-FU-treated mice was increased by SPR-901. All of the mice treated with 300 mg/kg of 5-FU in combination with SPR-901 survived over 15 days, however, only 4 of 10 mice treated only with 300 mg/kg of 5-FU survived. These results suggest that SPR-901 acts on macrophages directly or indirectly, giving rise to the enhanced production of IL-1, IL-6, and other factors. Some of the factors derived from SPR-901 activated macrophages, perhaps mainly IL-6, act on the early stage of development of multipotent bone marrow progenitors synergistically with GM-CSF.


Predicted response in food conversion ratio for growth by selection on the ratio or on linear component traits, in a (sequential) selection programme.
1. Direct versus indirect selection for food conversion ratio of growth (FCR) after selection for live body weight (LWT), a sequential scheme often applied in broilers, was considered. In the present study loss of response in either FCR or aggregate genotype (H) when LWT was included was investigated under selection on a linear index of ratio component traits (and LWT) or FCR (and LWT) by selection index methodology. 2. Relative responses in FCR and H were generally very similar under single-step and sequential selection. Without LWT in H, selection for linear index or ratio gave similar responses in FCR when heritabilities of components were equal. With large differences in heritabilities (0.2 compared with 0.5) or genetic and environmental correlation (> 0.6) significant differences in response (5 to 12%) in FCR emerged. Therefore, whether additional costs are justified for parameter and breeding value estimation when using a linear index in place of selection for the ratio depends on the difference in heritabilities and correlations of the ration component traits. With LWT in H, loss of response in FCR was partially or entirely offset by response in LWT. 3. The non-normality of FCR and consequences for (co)variance component estimation were studied in terms of the coefficients of variation of the component traits of FCR. Restricted Maximum Likelihood (REML) estimation of (co) variance components for both FCR and logarithm transformed FCR (closer to normality) showed the robustness of REML to such deviations from normality.


Dissociation of avian salt gland: separation procedures and characterization of dissociated cells.
A procedure for dissociation of the nasal salt glands of the domestic duck, Anas platyrhynchos, into suspensions of individual cells has been developed. This technique employs enzymatic digestion with collagenase, hyaluronidase, and chymotrypsin; divalent cation chelation with EDTA; and gentle mechanical dispersion. Average cellular yields of 39 and 26% based on DNA recovered were obtained from the glands of freshwater- and saline-adapted ducks, respectively. Epithelial secretory cells comprised 60-80% of the cell suspensions with the remainder of the populations consisting of endothelial cells, fibroblasts, and blood cells. The dissociated cells were viable as judged by trypan blue exclusion (80-100%, maintenance of ultrastructural integrity, and retention of responsiveness to secretagogues and metabolic inhibitors. Methacholine chloride (0.5 mM) stimulated oxygen consumption by suspensions of both freshwater- and saline-adapted cells, whereas ouabain (0.05 mM) abolished the methacholine-stimulated respiratory response. These cell suspensions provide a promising system for the in vitro study of secretory mechanisms in the avian salt gland.


Healing around implants placed in bone defects treated with Bio-Oss. An experimental study in the dog.
The aim of the present experiment was to (i) study the healing after 3 and 7 months of bone defects filled with cancellous bovine bone mineral and (ii) compare the healing around implants placed in normal bone and in defects filled with bovine bone mineral. 5 beagle dogs, about 1-year-old, were used. At baseline, extractions of all mandibular left and right premolars were performed. Bone defects were prepared in the left mandibular quadrant. The defect was immediately filled with natural bovine cancellous bone mineral particles (Bio-Oss, Geistlich Sons Ltd. Wolhusen, Switzerland). No resective surgery was performed in the right jaw quadrant. In both quadrants the flaps were adjusted to allow full coverage of the edentulous ridge and sutured. 3 months later, 2 dogs (group I) were euthanized and biopsies from the premolar regions obtained and prepared for histologic analysis. The 3 remaining dogs (group II) were at this time interval (3 months) subjected to implant installation in the premolar region of both the right and left mandibular jaw quadrants. 2 fixtures of the ITI Dental Implant System (Straumann, Waldenburg, Switzerland; solid-screw; 8 x 3.3 mm) were installed in each side. The fixtures in the test side were placed within the previously grafted defect area, while the fixtures in the control side were placed in normally healed extraction sites. A 4 month period of plaque control was initiated. At the end of this period, a clinical examination including assessment of plaque and soft tissue inflammation was performed and radiographs obtained from the implant sites. Biopsies were harvested and 4 tissue samples were yielded per dog, each including the implant and the surrounding soft and hard peri-implant tissues. The biopsies were processed for ground sectioning or "fracture technique" and the sections produced were subjected to histological examination. The volume of the hard tissue that was occupied by clearly identified Bio-Oss particles was reduced between the 3- and 7-month intervals. This indicates that with time, Bio-Oss becomes integrated and subsequently replaced by newly formed bone. In other words, this xenograft fulfils the criteria of an osteoconductive material. It was also observed that 4 months after implant installation, the titanium/hard tissue interface at test and control sites exhibited, from both a quantitative and qualitative aspect, a similar degree of "osseointegration".


[Heavy metal concentration in Nanjing urban soils and their affecting factors].
The concentration and source of heavy metals in Nanjing urban soils and their relationships with soil properties were studied. The results indicated that the soils in Nanjing urban were not obviously polluted by Fe, Ni, Co and V, but polluted by Mn, Cr, Cu, Zn, and Pb to a certain extent. The heavy metals were irregularly distributed in soil profiles. Fe, Ni, Co, and V were originated from soil materials, but Cu, Zn, Pb, and Cr were anthropogenic input. Probably, Mn had different origins in different soils. There were positive correlations among Fe, Cr, Ni, Co, and V concentration, and among Cu, Zn, Pb, and Cr concentration. The Fe, Co, V, and Ni concentration were positively correlated with soil clay content and CEC, and the Cu, Zn and Pb concentration were negatively correlated with clay content. There were positive correlations between Cu, Zn, Pb and Cr concentration and organic C content, and between Pb concentration and soil pH.


Neuraminidase inhibitors for preventing and treating influenza in children.
During epidemic years, influenza attack rates in children exceed 40%. Options for prevention and treatment include immunisation, amantadine and rimantadine, and the neuraminidase inhibitors: zanamivir and oseltamivir. Our objective was to assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prophylaxis of influenza infection in children. We searched the Cochrane Acute Respiratory Infections Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the GlaxoSmithKline Clinical Trials Register, generally from inception through to December 2002. We also screened the references of retrieved articles and scrutinised relevant web sites. We also screened references of retrieved articles and other systematic reviews, scrutinised web sites of European and US regulatory bodies, and contacted manufacturers and authors. Double-blind randomised controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs in children less than 12 years of age. Additional safety and tolerability data from other sources were also included. Four reviewers applied the inclusion criteria to the retrieved studies, assessed trial quality and extracted data. Data were analysed separately for oseltamivir and zanamivir. We identified three randomised controlled trials reporting data from 1500 children with a clinical case definition of influenza, of whom 798 had laboratory confirmed influenza infection. Two were trials of oseltamivir (in healthy children and in children with asthma) and one was a trial of zanamivir (in healthy children). Overall, trial quality was good. Oseltamivir reduced the median duration of illness by 26% (36 hours) in previously healthy children with laboratory confirmed influenza (p < 0.0001) and by 17% (21 hours) in the intention-to-treat population (p = 0.0002). Zanamivir reduced the median duration of illness by 24% (1.25 days) in previously healthy children with laboratory confirmed influenza (p < 0.001) and by 10% (0.5 days) in the intention-to-treat population (p = 0.011). Both drugs also significantly reduced the time to return to normal activity. Only oseltamivir produced a significant reduction in the complications of influenza (particularly otitis media), although there was a trend to benefit for zanamivir. No data on the use of zanamivir in 'at risk' children were available. The reduction in time to resolution of illness in 'at risk' children (with asthma) treated with oseltamivir was not statistically significant. Although we identified three trials of neuraminidase inhibitors in the prevention of influenza in families (including children), Roche and GlaxoSmithKline were not willing to break-out data for paediatric populations, and so no data were eligible for inclusion in the review. The adverse events profile of zanamivir was no worse than placebo and we found no reports of zanamivir-induced bronchospasm in children. Vomiting was more common in children treated with oseltamivir (p = 0.008), but study withdrawals were similar (<2%) between oseltamivir and placebo. Neuraminidase inhibitors were effective in shortening illness duration and hastening return to normal activity in previously healthy children with a clinical or laboratory diagnosis of influenza. Oseltamivir was effective in reducing the incidence of secondary complications. Efficacy in 'at risk' children remains to be proven. The drugs are safe, but oseltamivir can cause vomiting.


[Flow-cytofluorometric study of bactericidal granules in blood phagocytes of animals with various species sensitivity to experimental plague infection].
Compare the content of bactericidal granules (BG) in blood phagocytes of animals, that differ by species sensitivity to plague infection, under the conditions of measuring, that ensure automatic differentiating by this parameter of monocytes and granulocytes of human blood. Human whole blood leukocytes were studied, as well as from 7 animal species: mice, guinea pigs, golden hamsters, white rats, rabbits, dogs and horses. Acridine orange (AO) was used for supra-vital staining in primary (bactericidal) granule cells. Relative BG content was measured in separate cells in conventional units of red fluorescence intensity by flow cytofluorometry. Deficiency of AO molecules in BG, that correlates with deficiency of leukocyte elastase in cells, that is most pronounced in mice and lest pronounced in rabbits, was established to be characteristic for all the blood phagocytes of all the laboratory animal species sensitive to plague. Blood phagocytes of dogs and horses, that were non-sensitive to plague, differed by high heterogeneity by the studied parameter, and in horse blood innate immunity cells were detected, that contained 2.5 times higher amount of BG, than blood granulocytes of humans. Leukocyte BG, that have enzyme cationic proteins: elastase, cathepsin G, protease 3 and myeloperoxidase, play and important role in protection of organism from plague infection.


The effect of spousal bereavement on cognitive functioning in a sample of older adults.
This study examined the association between bereavement and cross-sectional differences in cognitive performance in a sample of older adults. Secondary cross-sectional data analysis was conducted on 211 participants from the MacArthur Battery dataset. Participants completed several cognitive tasks 6-months post-loss. Hierarchical multiple regression results suggested that bereavement status was not associated with cognitive performance. However, the effect of bereavement on memory (immediate and delayed story recall) performance was moderated by age and gender where the younger participants and men who were bereaved performed worse compared to their non-bereaved counterparts. Our results support the finding that bereavement is associated with poorer memory performance within certain subgroups (i.e., men and younger participants). We discuss findings in light of theories of stress and cognitive aging.