Basal metabolic rate in carnivores is associated with diet after controlling for phylogeny.
Studies of basal metabolic rate (BMR), the minimum metabolic rate of postabsorptive, inactive endotherms while in their rest phase and thermal neutral zone, have contributed significantly to our understanding of animal energetics. Besides body mass, the main determinant of BMR, researchers have invoked diet and phylogenetic history as important factors that influence BMR, although their relative importance has been controversial. For 58 species within the Carnivora, we tested the hypothesis that BMR is correlated with home range size, a proxy for level of activity, and diet, using conventional least squares regression (CLSR) and regression based on phylogenetic independent contrasts (PIC). Results showed that BMR of Carnivora was positively correlated with home range size after controlling for body mass, regardless of the statistical method employed. We also found that diet and mass-adjusted home range size were correlated. When we simultaneously tested the effect of diet and mass-adjusted home range on mass-adjusted BMR, home range size was insignificant because of its colinearity with diet. Then we eliminated home range size from our model, and diet proved to be significant with both CLSR and PIC. We concluded that species that eat meat have larger home ranges and higher BMR than species that eat vegetable matter. To advance our understanding of the potential mechanisms that might explain our results, we propose the "muscle performance hypothesis," which suggests that selection for different muscle fiber types can account for the differences in BMR observed between meat eaters and vegetarian species within the Carnivora.


Synthesis and characterization of a new asymmetric bis-porphyrinato lanthanide complex presenting mixed hydrophilic-hydrophobic properties and its precursor form.
The synthesis and spectroscopic characterization of a new family of heteroleptic porphyrinate double-deckers are reported. The investigated compounds are represented by the formulae La(III)H(TPyP)(TPP) and [La(III)(TMePyP)(TPP)]I(3). UV-vis spectroscopy of the title complexes confirms the presence of a strong pi-pi interaction between the macrocycles in each derivative. With (1)H and 2-D NMR data, we were able to distinguish two major NMR regions: the endo, between the bonded macrocycles, and the exo, outside the macrocycles, which are characteristic features of porphyrinic double-deckers. Finally, the electrochemical study confirms the strong pi-pi interaction for La(III)H(TPyP)(TPP) and completes this first approach for the investigation of this new family of derivatives.


Evaluation of early corneal endothelial cell loss in bimanual microincision cataract surgery (MICS) in comparison with standard phacoemulsification.
To analyze early corneal endothelial cell loss due to microincision cataract surgery (MICS) in comparison with standard phacoemulsification through the temporal clear corneal incision. The examined group consisted of a nonrandomized, consecutive prospective series of 20 eyes of 20 patients who underwent uneventful microincision cataract surgery. Twenty eyes of 20 patients who underwent standard phacoemulsification with foldable intraocular lens (IOL) implantation served as a reference group. Patients with corneal disorders, contact lens wear, previous intraocular surgery, and a history of ocular trauma were excluded from the study. Patients were examined preoperatively and 10 days postoperatively. The following items were evaluated in this study: corneal endothelial cell density, intraoperative phaco power, effective phaco time, as well as pre- and postoperative visual acuity. Corneal endothelial cell counts were done in the central part of the cornea using a non-contact Topcon SP 2000P specular microscope before and 10 days after the surgery. The measurements were performed in a semiautomated, masked manner. Statistical analysis was done using nonparametric tests (Wilcoxon signed-ranks test and Mann-Whitney U test). All patients in the study underwent uneventful surgery. Best-corrected visual acuity (BCVA) examined 10 days postoperatively in the MICS group was 0.94+/-0.094, whereas in the standard phacoemulsification group it was 0.90+/-0.094. There was no significant difference between BCVA in the two groups (Mann Whitney U two-tailed test: p>0.05). In both groups there was a significant decrease in postoperative endothelial cell densities (ECDs) when compared to preoperative values. Mean postoperative ECDs were 2235+/-418 cells/mm2 in the MICS group and 2079+/-399 cells/mm2 in the standard phacoemulsification group; the difference was not statistically significant (Mann-Whitney U test: p>0.05). Patients in the MICS group lost an average of 9.5% of cells, whereas patients after standard phacoemulsification lost about 7.6% of cells. This difference was statistically insignificant. Microincision cataract surgery induced corneal endothelial cell loss similar to a standard phacoemulsification and allowed excellent visual results in this series of patients. These results support the use of MICS technique for cataract surgery.


Local recurrence map to guide target volume delineation after radical prostatectomy.
To describe the various anatomic locations of recurrent disease, in a cohort of men with radiographically visualized, biopsy-proven recurrent prostate cancer after radical prostatectomy (RP), in order to help guide contouring of the prostatic fossa clinical target volume (PF-CTV) when no gross recurrence is visible or when magnetic resonance imaging (MRI) is not used. Ten representative patients with MRI-detected, biopsy-proven local recurrences of prostate adenocarcinoma after RP were selected. Areas of recurrence were delineated on individual MRI images, and then mapped onto axial and sagittal "template" MRI images to compositely demonstrate the documented areas of recurrence. Coverage of these anatomic areas of recurrence was then evaluated by applying Radiation Therapy Oncology Group (RTOG)-consensus PF-CTV contours to a postoperative computed tomographic template. The median age at the time of RP was 61 years (range, 50-73). In the superoinferior direction, recurrences ranged from the superior retrovesical region, to the inferior retrovesical region, to the posterior anastomosis, and as inferiorly as the posterior urogenital diaphragm. In the anteroposterior direction, the areas of recurrence ranged from involving the posterior bladder wall anteriorly to invading the rectum posteriorly. Recurrences were found at the center, right, and left of the prostate and seminal vesicle fossa. When target volumes were delineated using RTOG-defined consensus PF-CTV contours, coverage was marginal on recurrences in the posterolateral aspects of the CTV near the rectum and mesorectal fascia and lacking on recurrences occurring inferiorly at the posterior urogenital diaphragm. Our findings describe the variation in location of prostate cancer recurrences and can be used to improve target definition in conformal radiation therapy in the postoperative adjuvant or salvage setting. RTOG-consensus contours for the PF-CTV should be applied carefully, with potential modifications in the posterolateral and inferior aspects.


Physicochemical and biological properties of poly(ethylene glycol)-coupled immunoglobulin G.
In order to develop a new intravenous immunoglobulin G (IgG), IgG was covalently coupled to poly(ethylene glycol) previously activated by cyanuric chloride. The poly(ethylene glycol) coupled IgG obtained was studied for physicochemical and biological properties such as molecular structure, size-exclusion chromatographic behaviour, surface activity, interfacial aggregability, heat aggregability inducing nonspecific complement activation, and antigen-binding activity. The poly(ethylene glycol) coupling to IgG increased the apparent Stokes' radius and the surface activity of IgG and stabilized IgG on heating and/or on exposure to interface, while no structural denaturation of IgG was observed. The suppressed nonspecific aggregability was interpreted mainly by difficulty in association between the modified IgG molecules. These results indicated the use of the poly(ethylene glycol)-coupled IgG as an intravenous preparation and also as an additive stabilizing intact IgG for intravenous use.


Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in TUBB4A.
TUBB4A pathogenic variants are associated with a spectrum of neurologic impairments including movement disorders and leukodystrophy. With the development of targeted therapies, there is an urgent unmet need for validated tools to measure mobility impairment. Our aim is to explore gross motor function in a pediatric-onset TUBB4A-related leukodystrophy cohort with existing gross motor outcome tools. Gross Motor Function Measure-88 (GMFM-88), Gross Motor Function Classification System (GMFCS-ER), and Gross Motor Function Classification-Metachromatic Leukodystrophy (GMFC-MLD) were selected through face validity. Subjects with a confirmed clinical and molecular diagnosis of TUBB4A-related leukodystrophy were enrolled. Participants' sex, age, genotype, and age at disease onset were collected, together with GMFM-88 and concurrent GMFCS-ER and GMFC-MLD. Performances on each measure were compared. GMFM-88 floor effect was defined as total score below 20%. A total of 35 subjects participated. Median performance by GMFM-88 was 16.24% (range 0-97.31), with 42.9% (n = 15) of individuals performing above the floor. GMFM-88 Dimension A (Lying and Rolling) was the best-performing dimension in the GMFM-88 (n = 29 above the floor). All levels of the Classification Scales were represented, with the exception of the GMFC-MLD level 0. Evaluation by GMFM-88 was strongly correlated with the Classification Scales (Spearman correlations: GMFCS-ER:GMFM-88 r = 0.90; GMFC-MLD:GMFM-88 r = 0.88; GMFCS-ER:GMFC-MLD: r = 0.92). Despite overall observation of a floor effect, the GMFM-88 is able to accurately capture the performance of individuals with attenuated phenotypes. GMFM-88 Dimension A shows no floor effect. GMFC-MLD shows a strong correlation with GMFCS-ER and GMFM-88, supporting its use as an age-independent functional score in TUBB4A-related leukodystrophy.


Sex specific differences in fetal middle cerebral artery and umbilical venous Doppler.
The incidence of several adverse pregnancy outcomes including fetal growth restriction are higher in pregnancies where the fetus is male, leading to suggestions that placental insufficiency is more common in these fetuses. Placental insufficiency associated with fetal growth restriction may be identified by multi-vessel Doppler assessment, but little evidence exists regarding sex specific differences in these Doppler indices or placental function. This study aims to investigate sex specific differences in fetal and placental perfusion and to correlate these changes with intra-partum outcome. This is a prospective cohort study. We measured Doppler indices of 388 term pregnancies immediately prior to the onset of active labour (≤3 cm dilatation). Fetal sex was unknown at the time of the ultrasound assessment. Information from the ultrasound scan was not made available to clinical staff. Case notes and electronic records were reviewed following delivery. We report significantly lower Middle Cerebral artery pulsatility index (1.34 vs. 1.43, p = 0.004), Middle Cerebral artery peak velocity (53.47 cm/s vs. 58.10 cm/s, p = <0.001), and Umbilical venous flow/kg (56 ml/min/kg vs. 61 ml/min/kg, p = 0.02) in male fetuses. These differences however, were not associated with significant differences in intra-partum outcome. Sex specific differences in feto-placental perfusion indices exist. Whilst the physiological relevance of these is currently unknown, the identification of these differences adds to our knowledge of the physiology of male and female fetuses in utero. A number of disease processes have now been shown to have an association with changes in fetal haemodynamics in-utero, as well as having a sex bias, making further investigation of the sex specific differences present during fetal life important. Whilst the clinical application of these findings is currently limited, the results from this study do provide further insight into the gender specific circulatory differences present in the fetal period.


A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis.
The biosynthesis of photopyrones, novel quorum sensing signals in Photorhabdus, has been studied by heterologous expression of the photopyrone synthase PpyS catalyzing the head-to-head condensation of two acyl moieties. The biochemical mechanism of pyrone formation has been investigated by amino acid exchange and bioinformatic analysis. Additionally, the evolutionary origin of PpyS has been studied by phylogenetic analyses also revealing homologous enzymes in Pseudomonas sp. GM30 responsible for the biosynthesis of pseudopyronines including a novel derivative. Moreover this novel class of ketosynthases is only distantly related to other pyrone-forming enzymes identified in the biosynthesis of the potent antibiotics myxopyronin and corallopyronin.


Design, Synthesis and Biological Evaluation of Some 5-Arylthieno[2,3-d]pyrimidines as Potential Anti-cancer Agents.
Structure-based design, synthesis and biological evaluation of new small molecules anti-cancer agents were described. On continuation of applying scaffold hopping theory, a series of 5-arylthieno[2,3-d]pyrimidines based on the structural features of lapatinib was designed, synthesized and characterized using IR, (1)H-NMR, (13)C-NMR, mass and microanalyses. Biological evaluation of the cytotoxic activity against MCF-7 cell line and the inhibition of the enzymatic activity of epidermal growth factor tyrosine kinase were carried out in vitro for the target compounds. Substituting the 4-anilino-5-arylthieno[2,3-d]pyrimidines with different pharmacophoric groups at ortho, meta and/or para positions led to discovery of two potent lead compounds 3b and f with excellent cytotoxic activity and enzymatic inhibition activity.


Multivessel transradial percutaneous coronary angioplasty in a single coronary artery originating from the right sinus of Valsalva.
Percutaneous coronary intervention in patients with an anomalous coronary artery is technically challenging. Selective cannulation and coaxial positioning in the anomalous artery and optimum stability during the procedure are pivotal for successful completion of the procedure. Selection of the appropriate guide catheter is of paramount importance in these situations. In patients with congenital coronary artery anomalies, increasing use of multidetector computed tomography for cardiac imaging may yield diagnostic information not obtained with coronary angiography. Axial, multiplanar, and three-dimensional volume-rendered reconstructions aid in detecting and interpreting such anomalies and in selecting appropriate hardware during percutaneous coronary intervention in these patients. We report a case of successful stent implantation in the right coronary artery and proximal circumflex coronary artery in a patient with a single coronary artery arising from the right sinus of Valsalva.


A Clinical Approach to Diagnosis of Ambiguous Genitalia.
Disorders of sex development (DSD) are a sensitive and stressful condition for the family as well as the treating physician to deal with. The main issue in managing such cases is sex assignment. The decision is influenced by the cultural background, the sex of rearing, clinical features, the biochemical parameters including hormonal studies, the imaging reports, parental preference, fertility potential, and the assessment of mental make-up of the child when possible. In third world countries, there is diagnostic dilemma as most children with DSD present late and a detailed-lengthy work-up often delay their definitive treatment. In this article, the authors try to identify the important clinical features in children presenting with various types of DSD, which may aid in making a quick provisional clinical diagnosis and expediting the diagnostic work-up. The data have been gathered from 38 years of experience of the senior author while managing about 1200 cases of DSD in the pediatric intersex clinic at the tertiary care level institute.


GC-biased segregation of noncoding polymorphisms in Drosophila.
The study of base composition evolution in Drosophila has been achieved mostly through the analysis of coding sequences. Third codon position GC content, however, is influenced by both neutral forces (e.g., mutation bias) and natural selection for codon usage optimization. In this article, large data sets of noncoding DNA sequence polymorphism in D. melanogaster and D. simulans were gathered from public databases to try to disentangle these two factors-noncoding sequences are not affected by selection for codon usage. Allele frequency analyses revealed an asymmetric pattern of AT vs. GC noncoding polymorphisms: AT --> GC mutations are less numerous, and tend to segregate at a higher frequency, than GC --> AT ones, especially at GC-rich loci. This is indicative of nonstationary evolution of base composition and/or of GC-biased allele transmission. Fitting population genetics models to the allele frequency spectra confirmed this result and favored the hypothesis of a biased transmission. These results, together with previous reports, suggest that GC-biased gene conversion has influenced base composition evolution in Drosophila and explain the correlation between intron and exon GC content.


Chemically functionalized manufactured sand as the novel additive for enhancing the properties of cement-based composites.
The extensive applications of manufactured sand (AS) in cement-based composites were restricted because of its coarse surface texture, poor gradation and inevitable agglomeration. In this paper, a specifically designed polycarboxylate superplasticizer (PCE) decorated manufactured sand (AS-PCE) composite was synthesized via radical polymerization. The AS-PCE composite was characterized by FTIR, TGA, XPS and SEM. The load of PCE on the surface of AS was ∼12 wt%. Our results show that AS-PCE can promote cement hydration reaction and refine the microstructure of a cement-based material, thus, reinforcing its mechanical strength. Meanwhile, the fluidity of cement mortar with 1 wt% AS-PCE particles was increased by 35% after 1 h hydration, due to the steric hindrance effect provided by polycarboxylate superplasticizer affiliated with AS-PCE. The AS-PCE can also significantly enhance the mechanical strength (especially, the flexural strength was about 25% increased after curing for 28 days) of mortar. The excellent improvements result from the synergistic effects of AS-PCE including superb dispersibility, promotion of cement hydration reaction and the repair of interfacial defects between AS particles and the cementitious material. The research provides a promising method for the AS application in cement-based materials.


Organ trading, tourism, and trafficking within Europe.
This article argues for a regulatory and institutional response towards organ trading, tourism and trafficking that differs from extant approaches. European countries have hitherto adopted blanket prohibitions on organ trading (i.e. the buying or selling of human organs). This article advances the view that policy makers have thereby overreacted to legitimate public health concerns and the evils of organ trafficking (i.e. organ trading and tourism involving coercion or deception). It argues for a trial of a very tightly regulated system of organ trading that could eventually lead to a limited system of organ tourism (i.e. organ trading involving more than one jurisdiction).


Reliable indices for the determination of viability of grafted liver immediately after orthotopic transplantation. Bile flow rate and cellular adenosine triphosphate level.
One of the major problems accompanying liver transplantation is how to evaluate the viability of the grafted tissue at an early stage. The ability to assess immediate graft function would provide results useful in the determination of prognosis. The present study was undertaken to determine whether bile flow rates after liver transplantation were correlated with adenosine triphosphate levels and the survival of rats given transplants. In fresh-liver-transplanted rats, the one-week survival rate was 87%. The cellular ATP levels in the grafts decreased sharply prior to portal-venous declamping, but returned to nearly 80% of the normal level 4 hr after grafting, as did the total adenine nucleotide level and energy charge. When the grafts were subjected to warm ischemia for 15-min or 30-min periods prior to harvesting of the donor liver, the one-week survival rates decreased to 50% and 0%, respectively. In these cases, the levels of cellular ATP and bile secretion remained low and were proportional to the survival of the transplanted animals even 4 hr after transplantation. The relationship between the bile flow rates and the cellular ATP levels under various conditions revealed a good correlation, showing a saturation curve. The bile flow rates as well as the cellular ATP levels were therefore related to the survival rates of the transplanted animals. Thus it was shown in this experimental transplantation model that the monitoring of bile production after liver grafting is a useful indicator for assessing the extent of ischemic damage to the liver and for prognosis of the animal.


Direct arginine modification in native peptides and application to chemical probe development.
An efficient method for the direct labeling of the Arg guanidinium group in native peptides is reported. This straightforward procedure allows modifying the arginine moiety in peptides with various reporter groups, such as fluorophores, biotin, etc., under mild conditions in an operationally simple procedure. The scope of this method tolerates various functionalized amino acids such as His, Ser, Trp, Tyr, Glu, etc., while the only limitations uncovered so far are restricted to cysteine and free amine residues. The utility of this late-stage diversification method was demonstrated in direct labeling of leuprolide, a clinically used drug, for distribution monitoring in Daphnia, and in labeling of microcystin, a cyanobacterial toxin.


Genetic analysis of Porphyromonas gingivalis (fimA), Aggregatibacter actinomycetemcomitans, and red complex in coronary plaque.
The objective of the present study was to detect the presence of Porphyromonas gingivalis (fimA), Aggregatibacter actinomycetemcomitans, and red complex in the coronary plaque of patients with coronary artery disease. The study population consisted of 51 patients with chronic periodontitis undergoing coronary artery bypass grafting. DNA was extracted from subgingival and coronary atherosclerotic plaque samples. Polymerase chain reaction was used to amplify the part of 16S rRNA gene to detect the presence of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis (fimA), Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, Porphyromonas gingivalis (fimA), and Treponema denticola were detected in 0%, 31.4%, 45.1%, 39.2%, and 51% of the atherosclerotic plaque samples, respectively. In both subgingival and coronary atherosclerotic plaque samples, Tannerella forsythia was detected in 19.6%, Porphyromonas gingivalis in 39.2%, Porphyromonas gingivalis (fimA) in 33.3%, and Treponema denticola in 35.3% of the samples. The study confirmed the detection of red complex bacteria in coronary plaque samples. However Aggregatibacter actinomycetemcomitans could not be detected in these samples.


The optical properties of alpha 2-macroglobulin from normal and from cystic fibrosis plasma.
The alpha 2-macroglobulin (alpha 2-M) was purified from the plasma of normal individuals and from that of cystic fibrosis patients. The proteins exhibited identical optical properties. Both proteins have an absorbance coefficient of A = 1060 g . cm-2 at 280 nm. The circular dichroism spectra are identical and indicate about 45% beta-sheet structure and almost no alpha-helix. The spectra of solutions at pH 8.0 do not change when trypsin is added. The fluorescence spectra of the alpha 2-M measured at pH 8.0 have contributions by tyrosine and tryptophan residues. The fluorescence intensities are identical and are enhanced about 30% when trypsin is added in 2:1 molar ratios.


On the synthesis and physical properties of iron doped SnO2 nanoparticles.
The synthesis of iron doped tin oxide by pulsed laser pyrolysis is reported. The as obtained nanoparticles have a dominant SnO2 phase (as revealed by Wide Angle X-ray Scattering), with particles of the order of 10 nm. The doping with iron or iron oxide triggers magnetic properties as confirmed by SQUID experiments. EDX measurements supported the presence of Fe while Wide Angle X-ray Scattering failed to sense any iron or iron-oxide phase. It is concluded that Fe is well dispersed within the tin-oxide nanoparticles. The coercitive field has a complex dependence on the Fe/Sn content suggesting that the magnetization is not controlled solely by the amount of Fe dispersed within the nanoparticles.


The influence of individual differences in sensitivity to provocations on provoked aggression.
Using an adapted form of the Taylor Competitive reaction Time (TCRT) task [Taylor (1967). Journal of Personality, 35, 297-310], this study is the first to examine the influence of individual differences in sensitivity to provocations (SP) [Lawrence (2006). Aggressive Behavior, 32, 3, 241-252] as opposed to sensitivity to frustrations (SF) on provoked aggression (noise blasts delivered to a bogus partner). Participants (N = 144) played a competitive reaction time task against a bogus partner, who delivered increasingly loud noise blasts to participants on trials when the participant lost. The study also manipulated the partner's behavior such that, in initial trials, the partner either delivered moderate blasts to the participant or no blasts at all. While accounting for broad trait aggression, those high in SP delivered louder noise blasts to a bogus partner when provoked but not when unprovoked. These individuals also delivered more maximum blasts to the partner and delivered maximum blasts earlier in the TCRT. The effects of SP became non-significant when the partner was initially non-aggressive. Similarly, an initially non-aggressive partner reduced participant aggression under later conditions of moderate provocation from the partner, but this effect became non-significant under subsequent high provocation from the partner. While being related to SP, SF did not influence provoked aggression.


Evaluation of Tumor Blood Flow Using Alternate Ascending/Descending Directional Navigation in Primary Brain Tumors: A Comparison Study with Dynamic Susceptibility Contrast Magnetic Resonance Imaging.
Alternate ascending/descending directional navigation (ALADDIN) is a novel arterial spin labeling technique that does not require a separate spin preparation pulse. We sought to compare the normalized cerebral blood flow (nCBF) values obtained by ALADDIN and dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) in patients with primary brain tumors. Sixteen patients with primary brain tumors underwent MRI scans including contrast-enhanced T1-weighted imaging, DSC perfusion MRI, and ALADDIN. The nCBF values of normal gray matter (GM) and tumor areas were measured by both DSC perfusion MRI and ALADDIN, which were compared by the Wilcoxon signed rank test. Subgroup analyses according to pathology were performed with the Wilcoxon signed rank test. Higher mean nCBF values of GM regions in the bilateral frontal lobe, temporal lobe, and caudate were detected by ALADDIN than by DSC perfusion MRI (p <0.05). In terms of the mean or median nCBF values and the mean of the top 10% nCBF values from tumors, DSC perfusion MRI and ALADDIN did not statistically significantly differ either overall or in each tumor group. ALADDIN tended to detect higher nCBF values in normal GM, as well as higher perfusion portions of primary brain tumors, than did DSC perfusion MRI. We believe that the high perfusion signal on ALADDIN can be beneficial in lesion detection and characterization.


[Comparison of pulse oxygen saturation/fraction of inhaled oxygen and arterial partial pressure of oxygen/fraction of inhaled oxygen in the assessment of oxygenation in acute respiratory distress syndrome patients at different high altitudes in Yunnan Province].
To investigate and evaluate if pulse oxygen saturation/fraction of inhaled oxygen (SpO2/FiO2) can be used, as replacement of arterial partial pressure of oxygen/fraction of inhaled oxygen (PaO2/FiO2), to assess oxygenation in acute respiratory distress syndrome (ARDS) patients at different high altitudes in Yunnan Province, and to find a rapid and non-invasive method for the diagnosis of ARDS at different altitudes. Patients with ARDS at different high altitudes in Yunnan Province from January 2019 to December 2020 were enrolled. The patients were divided into three groups according to different altitudes, and received different oxygen therapies according to their respective medical conditions. Group 1 consisted of patients with moderate to severe ARDS from the department of critical care medicine of the First Affiliated Hospital of Kunming Medical University (average altitude approximately 1 800 m), and received mechanical ventilation to maintain SpO2 of 0.90-0.96 with a low FiO2 for more than 30 minutes, and SpO2, FiO2, PaO2 were recorded. Group 2 consisted of patients with moderate to severe ARDS at the department of critical care medicine of People's Hospital of Diqing Tibetan Autonomous Prefecture (mean altitude about 3 200 m), and received oxygen with an attached reservoir mask to maintain SpO2 of 0.90-0.96 for 10 minutes, and then SpO2, FiO2, and PaO2 were recorded. Group 3 consisted of patients with mild to moderate-severe ARDS who admitted to the emergency department of the People's Hospital of Lijiang (average altitude approximately 2 200 m); when SpO2 < 0.90, patients received oxygen with the oxygen storage mask, and the FiO2 required to maintain SpO2 ≥ 0.90 was recorded, and SpO2, FiO2, PaO2 were recorded after oxygen inhalation for 10 minutes. Spearman coefficient was used to analyze the correlation between SpO2/FiO2 and PaO2/FiO2 in each group. Linear analysis was used to derive the linear equation between SpO2/FiO2 and PaO2/FiO2, and to evaluate arterial pH, arterial partial pressure of carbon dioxide (PaCO2), FiO2, tidal volume (VT), positive end-expiratory pressure (PEEP) and other related factors which would change the correlation between SpO2/FiO2 and PaO2/FiO2. The receiver operator characteristic curve (ROC curve) was plotted to calculate the sensitivity and specificity of using SpO2/FiO2 instead of PaO2/FiO2 to assess oxygenation of ARDS patients. Group 1 consisted of 24 ARDS patients from whom 271 blood gas analysis results were collected; group 2 consisted of 14 ARDS patients from whom a total of 47 blood gas analysis results were collected; group 3 consisted of 76 ARDS patients, and a total of 76 blood gas analysis results were collected. The PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa) in groups 1, 2 and 3 were 103 (79, 130), 168 (98, 195) and 232 (146, 271) respectively, while SpO2/FiO2 were 157 (128, 190), 419 (190, 445) and 319 (228, 446) respectively. Among the three groups, patients in group 1 had the lowest PaO2/FiO2 and SpO2/FiO2, while patients in group 3 had the highest. Spearman correlation analysis showed that PaO2/FiO2 was highly correlated with SpO2/FiO2 in groups 1, 2 and 3 (r values were 0.830, 0.951, 0.828, all P < 0.05). Regression equation was fitted according to linear analysis: in group 1 SpO2/FiO2 = 58+0.97×PaO2/FiO2 (R2 = 0.548, P < 0.001); in group 2 SpO2/FiO2 = 6+2.13×PaO2/FiO2 (R2 = 0.938, P < 0.001); in group 3 SpO2/FiO2 = 53+1.33×PaO2/FiO2 (R2 = 0.828, P < 0.001). Further analysis revealed that PEEP, FiO2, and arterial blood pH could affect the correlation between SpO2/FiO2 and PaO2/FiO2. ROC curve analysis showed that the area under ROC curve (AUC) was 0.848 and 0.916 in group 1 with moderate to severe ARDS; based on the regression equation, the corresponding SpO2/FiO2 cut-off values at a PaO2/FiO2 of 100 mmHg and 200 mmHg were 155, 252 with a sensitivity of 84.9% and 100%, specificity of 87.2% and 70.6%, respectively. Patients with moderate to severe ARDS in group 2 (AUC was 0.945 and 0.977), the corresponding SpO2/FiO2 cut-off values at PaO2/FiO2 of 100 mmHg and 200 mmHg were 219 and 432 with the sensitivity of 100% and 85.2%, specificity of 82.5% and 100%, respectively. Patients with mild to moderate-severe ARDS in group 3 (AUC was 0.903 and 0.936), the corresponding SpO2/FiO2 cut-off values at a PaO2/FiO2 of 200 mmHg and 300 mmHg were 319 and 452 with the sensitivity of 100% and 100%, specificity of 80.9% and 86.2%, respectively. SpO2/FiO2 and PaO2/FiO2 in ARDS patients at different high altitudes in Yunnan Province have a good correlation, and non-invasive SpO2/FiO2 can be used to replace PaO2/FiO2 to assess the oxygenation in ARDS patients.


Optoelectronic and magnetic properties of Mn-doped and Mn-C co-doped Wurtzite ZnS: a first-principles study.
In order to meet the requirement of spintronic and optoelectronic, we have systematically investigated the effect of Mn doping and co-doping of Mn with C on the electronic, magnetic and optical properties of wurtzite zinc sulfide (ZnS) using first principle calculations. Our results find that single Mn doping alters the non-magnetic ZnS to a magnetic one and keeps its semiconducting and a semiconductor to half-metal transition is observed for Mn-C co-doping. Furthermore, an antiferromagnetic (AFM) and ferromagnetic (FM) ground states are favorable for Mn-doped and Mn-C co-doped system, respectively. Additionally, the optical properties of our studied configuration have been calculated in terms of real and imaginary parts of the complex dielectric function, absorption coefficient, and reflectivity. The absorption edge shifts slightly toward lower energy and intensity of the main peak become weak for single Mn doping, and a sharp peak at low energy is observed for the Mn-C co-doping. The analysis of optical absorption of Mn ions doped system shows the blue- and red-shifts of the d-d transition in the AFM and FM coupled of Mn ions doped configuration, respectively which is in good agreement with the experimental observations. The improved magnetic and optical properties of Mn-C co-doped ZnS shed light on the future application of such kind of materials in spintronic and optoelectronic devices such as remote sensing and photovoltaics.


Doped tricalcium phosphate scaffolds by thermal decomposition of naphthalene: Mechanical properties and in vivo osteogenesis in a rabbit femur model.
Tricalcium phosphate (TCP) is a bioceramic that is widely used in orthopedic and dental applications. TCP structures show excellent biocompatibility as well as biodegradability. In this study, porous β-TCP scaffolds were prepared by thermal decomposition of naphthalene. Scaffolds with 57.64% ± 3.54% density and a maximum pore size around 100 μm were fabricated via removing 30% naphthalene at 1150°C. The compressive strength for these scaffolds was 32.85 ± 1.41 MPa. Furthermore, by mixing 1 wt % SrO and 0.5 wt % SiO2 , pore interconnectivity improved, but the compressive strength decreased to 22.40 ± 2.70 MPa. However, after addition of polycaprolactone coating layers, the compressive strength of doped scaffolds increased to 29.57 ± 3.77 MPa. Porous scaffolds were implanted in rabbit femur defects to evaluate their biological property. The addition of dopants triggered osteoinduction by enhancing osteoid formation, osteocalcin expression, and bone regeneration, especially at the interface of the scaffold and host bone. This study showed processing flexibility to make interconnected porous scaffolds with different pore size and volume fraction porosity, while maintaining high compressive mechanical strength and excellent bioactivity. Results show that SrO/SiO2 -doped porous TCP scaffolds have excellent potential to be used in bone tissue engineering applications.


The remediation of conduction aphasia via sentence repetition: a case study.
Repetition is viewed typically as a primary deficit in conduction aphasia. Consequently, repetition is considered to be a target of treatment, as opposed to an approach to treatment for this syndrome. However, our experience with a conduction aphasic who had greater speech fluency in repetition than in conversation encouraged us to develop a treatment programme based on sentence repetition. The treatment programme has three components: (1) a pre-/post-test of sentence repetition; (2) the treatment component, in which a new set of sentences is introduced each week in outpatient therapy for daily repetition; (3) analysis of verbal picture description prior to and following treatment as an independent language measure. The patient CM participated in 2 months of sentence repetition treatment, after which he displayed improvement in both sentence repetition and picture description. The reasons for such improvement and the general utility of the treatment programme are discussed.


[The hemodynamic investigation of refractory septic shock-related cardiac dysfunction].
To research and analyze the hemodynamic status of refractory septic shock associated cardiac dysfunction. 70 refractory septic shock patients were studied. In the duration of pulmonary artery catheter (PAC)-directed hemodynamic optimization, the patients were divided into a cardiac dysfunction group and a control group. Hemodynamic parameters, arterial blood lactate concentration and APACHE II scores were obtained instantly after the placement of a PAC, then lactate clearance in 24 hours was surveyed and calculated. Subsequently the two groups of patients were regrouped by nonsurvivor and survivors respectively. All the obtained values were analyzed with statistic methods. 37% of the refractory septic shock patients was complicated with cardiac dysfunction. The age of the patients complicated with cardiac dysfunction was significantly higher than that of the patients of the control group. Central venous pressure (CVP), pulmonary artery obstruction pressure (PAOP), pulmonary artery pressure (PAP), systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI) and oxygen extraction ratio (O2ext) in the cardiac dysfunction group were significantly different from those in the control group. Cardiac output (CO), cardiac index (CI), oxygen delivery index (DO2I) and mixed venous oxygen saturation (SvO2) were significantly lower than those of the patients in the control group. SvO2 had a strong correlation with CI. If the patients were regrouped by nonsurvivors and survivors, in the patients complicated with cardiac dysfunction APACHE II scores were significantly higher in the nonsurvivors than survivors; the lactate clearance in 24 hours (median--25%) of the nonsurvivors was significantly lower than that of nonresponders (median 22%), P < 0.05. Conclusion (1) In refractory septic shock patients, cardiac dysfunction maybe the main reason leading to bad outcome. (2) Higher CVP and PAOP and lower SvO2 indicate the onset of cardiac dysfunction. (3) The patients with significantly high initial arterial blood lactate level and the low lactate clearance in 24 hours had bad outcome.


Interferon-gamma renders tumors that express low levels of Her-2/neu sensitive to cytotoxic T cells.
Her-2/neu is a tumor-associated antigen that has been targeted with both antibodies and cytotoxic T lymphocytes (CTL). Despite the isolation of Her-2/neu-reactive CTL in vaccinated patients, their therapeutic use has been limited by the observation that they often do not robustly recognize Her-2/neu(+) tumors. We sought to determine the mechanism for this escape using Ag201P and Ag201M cells, which are murine osteosarcoma tumor lines that express a functional HLA-A2/K(b) molecule. We now demonstrate that Ag201P and Ag201M express low levels of murine Her-2/neu, and that Ag201M was modestly and inconsistently recognized by an HLA-A2-restricted, Her-2/neu-reactive human CTL clone. In order to determine whether inefficient antigen processing might account for the weak recognition, COS-A2 cells were transfected with a short Her-2/neu minigene coding for the immunodominant Her-2/neu:369 epitope that did not require antigen processing or a long Her-2/neu minigene that did require antigen processing. Her-2/neu-reactive CTL clones only recognized COS-A2 cells transfected with the short minigene, indicating that lack of proper antigen processing could be responsible for the poor recognition of target cells. To confirm these results, it was demonstrated that following treatment with interferon-gamma, both Ag201P and Ag201M robustly and consistently stimulated the CTL clones. Furthermore, CTL clone recognition was enhanced following interferon-gamma treatment using another murine tumor line that expressed low levels of Her-2/neu (B16-A2/K(b)). The enhanced recognition of Ag201P and Ag201M in the presence of interferon-gamma was not due to an upregulation of Her-2/neu protein expression. Collectively, these results suggest that inefficient antigen processing of Her-2/neu can contribute to the lack of tumor recognition by CTL. These results also suggest that even tissues that express low levels of Her-2/neu might become CTL targets under conditions in which antigen processing is enhanced.


[Prophylactic surgery of mammary and ovarian carcinoma].
New insights into the genetic basis of carcinogenesis have been obtained by modern molecular biological techniques. Several susceptibility genes are known. The hereditary breast and ovarian cancer syndrome (germline mutations in BRCA1 and BRCA2) and endometrial cancer in the context of the hereditary non-polyposis colorectal cancer syndrome (HNPCC), germline mutations in mismatch-repair genes, are the most frequent hereditary cancer syndromes in gynaecology. Mutations in TP53 (Li-Fraumeni syndrome) and PTEN (Cowden's disease), associated with increased risk of breast cancer, are responsible for a smaller portion of familial breast cancer. The risk of inheritance and disease can be identified and defined by investigating family history, risk calculation programs, and genetic testing. Afterwards, options of primary, secondary, and tertiary prevention can be formulated. Presently, prophylactic surgery is the only option proven by clinical trials that can reduce the mortality of hereditary breast and ovarian cancer.


Effect of polylactic film (Surgi-Wrap) on preventing postoperative ileus after major hepato-pancreato-biliary surgery.
Major hepato-pancreato-biliary (HPB) surgery is usually performed via an open method rather than a laparoscopic method. Postoperative ileus (POI) is a classic complication after open surgery. The purpose of this study was to determine whether polylactic film is useful in the prevention of POI. A total of 179 patients who underwent major HPB surgery between 2005 and 2014, were retrospectively reviewed. A diagnosis of POI was made by a physical examination, laboratory, and radiological findings. Surgi-Wrap® polylactic film was preferentially used intraperitoneally by surgeons, just before wound closure. Major HPB surgery included pancreatoduodenectomy (n=48), distal or subtotal pancreatectomy (n=24), hepatectomy (n=67), other bile duct or gallbladder operations (n=35), and others (n=5). Although patients with polylactic film showed a significantly lower incidence of POI (n=3, 4.1% vs. n=14, 13.3%, p=0.041), they showed a significantly higher complication rate (n=20, 27.0% vs. n=19, 18.1%, p=0.004), particularly intra-abdominal fluid collection (n=7, 9.4% vs. n=2, 1.9%), and wound infections (n=6, 8.1% vs. n=3, 2.9%), than those who did not receive the film, respectively. Although the polylactic film prevented POI, more complications other than POI were observed. Well-designed randomized controlled trials, using this anti-adhesive product, are needed to evaluate its effect on POI after major HPB surgery.


Immunological and anti-viral therapy of chronic hepatitis B virus infection.
Although we have reached the stage when we can influence viral replication and some aspects of the immune response to the viral antigens, no practical and effective therapeutic regimen has been evolved. The next few years should, however, see considerable advances in this field, perhaps with combined anti-viral and immunostimulant regimens. The need to consider the infectivity of the patient, the risk of developing clinically significant chronic liver disease and the risk of developing clinically significant chronic liver disease and the risk of developing primary liver cell carcinoma in each patient may dictate that different regimens will be needed for HBe antigen-positive and negative carriers and for patients with chronic active or chronic persistent hepatitis and carriers with normal liver histology.


Gains and losses of small incision lateral total hip arthroplasty: what the patients want and its index case result.
A poll was initially attempted to elucidate what type of skin incision would be preferred by the patients. The retrospective analysis of index cases was preformed to reveal the gains and losses of small incision transgluteal THA. We performed a poll on the preferred type of skin incision to the patients, their families and the medical personnel in orthopedic department in a face-to-face manner. According to the result of the poll, we changed approaches from a standard transgluteal to a small incision transgluteal approach. Each 20 consecutive index patients that underwent standard or small-incision transgluteal THA were followed and compared for more than 2 years. The small incision THA group showed more rapid mobilization, shorter hospital stay, and better early satisfaction. However, no clinical benefits of small incision were observed after 6-weeks postoperatively. There were significant variations in implant alignments. More early major complications such as dislocation, intraoperative femoral fracture or leg length inequalities occurred in the small incision group. The use of a small incision in THA resulted in subtle and temporary gains, at the cost of several major early complications. Now we perform THA with definitely smaller incision than before but we do believe that performing a stable and well-aligned THA is far more important than the length or amount of surgical dissection.


The design, implementation and acceptability of an integrated intervention to address multiple behavioral and psychosocial risk factors among pregnant African American women.
African American women are at increased risk for poor pregnancy outcomes compared to other racial-ethnic groups. Single or multiple psychosocial and behavioral factors may contribute to this risk. Most interventions focus on singular risks. This paper describes the design, implementation, challenges faced, and acceptability of a behavioral counseling intervention for low income, pregnant African American women which integrated multiple targeted risks into a multi-component format. Six academic institutions in Washington, DC collaborated in the development of a community-wide, primary care research study, DC-HOPE, to improve pregnancy outcomes. Cigarette smoking, environmental tobacco smoke exposure, depression and intimate partner violence were the four risks targeted because of their adverse impact on pregnancy. Evidence-based models for addressing each risk were adapted and integrated into a multiple risk behavior intervention format. Pregnant women attending six urban prenatal clinics were screened for eligibility and risks and randomized to intervention or usual care. The 10-session intervention was delivered in conjunction with prenatal and postpartum care visits. Descriptive statistics on risk factor distributions, intervention attendance and length (i.e., with < 4 sessions considered minimal adherence) for all enrolled women (n = 1,044), and perceptions of study participation from a sub-sample of those enrolled (n = 152) are reported. Forty-eight percent of women screened were eligible based on presence of targeted risks, 76% of those eligible were enrolled, and 79% of those enrolled were retained postpartum. Most women reported a single risk factor (61%); 39% had multiple risks. Eighty-four percent of intervention women attended at least one session (60% attended > or = 4 sessions) without disruption of clinic scheduling. Specific risk factor content was delivered as prescribed in 80% or more of the sessions; 78% of sessions were fully completed (where all required risk content was covered). Ninety-three percent of the subsample of intervention women had a positive view of their relationship with their counselor. Most intervention women found the session content helpful. Implementation challenges of addressing multiple risk behaviors are discussed. While implementation adjustments and flexibility are necessary, multiple risk behavioral interventions can be implemented in a prenatal care setting without significant disruption of services, and with a majority of referred African American women participating in and expressing satisfaction with treatment sessions.


Tumor Targeting by Fusobacterium nucleatum: A Pilot Study and Future Perspectives.
Colorectal adenocarcinoma (CRC) is a common tumor with high mortality rates. Interestingly, CRC was found to be colonized by the oral anaerobic bacteria Fusobacterium nucleatum, which accelerates tumor progression and enables immune evasion. The CRC-specific colonization by fusobacteria is mediated through the recognition of tumor displayed Gal-GalNAc moieties by the fusobacterial Fap2 Gal-GalNAc lectin. Here, we show high Gal-GalNAc levels in additional adenocarcinomas including those found in the stomach, prostate, ovary, colon, uterus, pancreas, breast, lung, and esophagus. This observation coincides with recent reports that found fusobacterial DNA in some of these tumors. Given the tumorigenic role of fusobacteria and its immune evasion properties, we suggest that fusobacterial elimination might improve treatment outcome of the above tumors. Furthermore, as fusobacteria appears to specifically home-in to Gal-GalNAc-displaying tumors, it might be engineered as a platform for treating CRC and the above common, lethal, adenocarcinomas.


[Dilated cardiomyopathy: indication and role of invasive evaluation].
Coronary angiography is still the first choice method for the diagnosis of coronary artery disease in patients with dilated cardiomyopathy. The diagnosis of coronary artery disease is, in its turn, essential as patients with associated coronary artery disease have a worse prognosis, compared to patients with idiopathic dilated cardiomyopathy, and, more importantly, coronary revascularization may significantly improve left ventricular function, clinical symptoms and prognosis, when performed in the presence of a significant amount of viable myocardium. The favorable effects on the left ventricular function are greater when a contractile reserve is shown. However, revascularization of viable myocardium may have other beneficial effects like a reduction in left ventricular remodeling and in the incidence of recurrent ischemic events and malignant arrhythmias. The detection of viable myocardium should, however, be preceded by the detection of coronary artery disease through coronary angiography. The clinical history and the results of the non-invasive evaluation, with the possible exception of coronary calcium detection by electron beam computed tomography, do not, in fact, allow the diagnosis of coronary artery disease. Coronary angiography is thus indicated in all the patients with suspected coronary artery disease (e.g. males > 35 years, with coronary risk factors, a history of chest pain and/or regional wall motion abnormalities and/or perfusion defects at stress scintigraphy) in whom the age and general conditions warrant a coronary revascularization procedure. Coronary angiography is also indicated in all the patients who are candidates to heart transplantation or whose symptoms are secondary to a mechanical complication of myocardial infarction.


Two Synthetic Replicators Compete To Process a Dynamic Reagent Pool.
Complementary building blocks, comprising a set of four aromatic aldehydes and a set of four nucleophiles-three anilines and one hydroxylamine-combine through condensation reactions to afford a dynamic covalent library (DCL) consisting of the eight starting materials and 16 condensation products. One of the aldehydes and, consequently, all of the DCL members derived from this compound bear an amidopyridine recognition site. Exposure of this DCL to two maleimides, Mp and Mm, each equipped with a carboxylic acid recognition site, results in the formation of a series of products through irreversible 1,3-dipolar cycloaddition reactions with the four nitrones present in the DCL. However, only the two cycloadducts in the product pool that incorporate both recognition sites, Tp and Tm, are self-replicators that can harness the DCL as feedstock for their own formation, facilitating their own synthesis via autocatalytic and cross-catalytic pathways. The ability of these replicators to direct their own formation from the components present in the dynamic reagent pool in response to the input of instructions in the form of preformed replicators is demonstrated through a series of quantitative 19F{1H} NMR spectroscopy experiments. Simulations establish the critical relationships between the kinetic and thermodynamic parameters of the replicators, the initial reagent concentrations, and the presence or absence of the DCL and their influence on the competition between Tp and Tm. Thus, we establish the rules that govern the behavior of the competing replicators under conditions where their formation is coupled tightly to the processing of a DCL.


Pectenotoxin-2 abolishes constitutively activated NF-kappaB, leading to suppression of NF-kappaB related gene products and potentiation of apoptosis.
Although pectenotoxin-2 (PTX-2) is known to modify the actin cytoskeleton, very little is known about its apoptosis mechanism. In this study, we investigated whether PTX-2 induces apoptotic effects through suppression of the NF-kappaB signaling pathway in several leukemia cell types. PTX-2 significantly induced growth inhibition and apoptosis in a dose-dependent manner. Treatment with PTX-2 also significantly increased caspase-3 activity and poly (ADP-ribose) polymerase (PARP) cleavage, however caspase-3 inhibitor z-DEVD-fmk significantly inhibited PTX-2-induced cell death. These data suggest that the activation of caspase-3 is associated with PTX-2-induced apoptosis. NF-kappaB has also been shown to inhibit apoptosis in response to chemotherapeutic agents. As examined by the DNA-binding of NF-kappaB activation, we found that PTX-2 suppressed constitutive NF-kappaB activation and determined by p65 and p50 nuclear translocation, and IkappaBalpha degradation through dephosphorylation of Akt. Attenuation of constitutive NF-kappaB activity by pretreatment with pyrrolidine dithiocarbamate (PDTC), an NF-kappaB nuclear translocation inhibitor, induced significantly apoptosis in the presence of PTX-2. In addition, treatment of PTX-2 down-regulated NF-kappaB-dependent gene expression, Cox-2, IAP-1, IAP-2 and XIAP, at the transcriptional and translational level. Taken together, these results suggest that anti-cancer activities induced by PTX-2 may be mediated in part through suppression of constitutive NF-kappaB activity.


A dual-mobility cup reduces risk of dislocation in isolated acetabular revisions.
Isolated acetabular revisions using standard cups are at risk of dislocation. The introduction of a nonconstrained dual-mobility cup was designed to improve prosthetic stability without increasing loosening rates, but it is unclear whether the risk of dislocation is reduced. We therefore determined: (1) if the rate of dislocation in isolated acetabular revisions is lower with a dual-mobility cup, (2) implant survival, (3) patient function, and (4) radiographic incidence of migration, loosening, and osteolysis. We prospectively followed 33 selected patients who underwent isolated acetabular revisions with a minimum of 2 years' followup (mean, 3 years; range, 2-5 years). In 24 patients a stainless steel dual-mobility cup was cemented into an antiprotrusio cage, whereas in nine we used a hyaluronan dual-mobility revision cup with a foramen hook and superior and posterior flanges screw fixations. We determined Harris hip (HHS) and WOMAC scores and examined radiographs for migration, loosening, and osteolysis. There were no dislocations. Survivorship rates of the femoral and acetabular components were 97% at 5 years; the rerevision rate for any reason was 3%. At last followup, the mean HHS increased from 48 points preoperatively to 86 points. No patients had progressive osteolysis, component migration, or loosening on radiographs. In this select group of isolated acetabular revisions, our data suggest the use of a dual-mobility cup reduced the risk of dislocation without increasing loosening from 2 to 5 years. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


Effect of a free sulphydryl group on expression of HLA-B27 specificity.
Sequence studies indicate that the alpha-1 domain of the HLA-B27 molecule has a characteristic unpaired cysteine residue at position 67, adjacent, because of secondary structure, to a lysine at position 70. Simple chemical considerations predict that this cysteine should have an exceptionally reactive sulphydryl group. We have shown by ELISA and flow cytometry that the binding of some monoclonal antibodies to B27 on lymphoid cell lines can be inhibited by reagents which react with sulphydryl groups. However this inhibition is never complete: the evidence suggests 2 forms of B27 molecule, one of which is already blocked. We propose that some HLA molecules with oxidised sulphydryls are recognised as different from the reduced forms. Whether they are also recognised as foreign will depend on an individual's history of thymic learning. Oxidation to 'foreign' HLA in the adult is likely to predispose to inflammatory reactions.


Endothelial nitric oxide synthase and its negative regulator caveolin-1 localize to distinct perinuclear organelles.
Caveolin-1 is a member of a subset of intracellular proteins that regulate endothelial nitric oxide synthase (eNOS) activity. In caveolae, caveolin-1 inhibits eNOS activity via a direct interaction with the enzyme. Previous work has indicated that both eNOS and caveolin-1 are also localized at the perinuclear Golgi complex. Whether caveolin-1 is involved in eNOS regulation in this cell compartment is unknown. Here we studied the localization of eNOS and caveolin-1 in the perinuclear region of primary bovine aortic endothelial cells. By immunofluorescence microscopy we show that both eNOS and caveolin-1 co-localize with Golgi markers. On treatment of the cells with the microtubule-depolymerizing drug nocodazole, the Golgi complex is scattered and caveolin-1 is found in vesicles at the periphery of the cell, while eNOS is localized at large structures near the nucleus. The nocodazole-induced redistribution of eNOS is similar to that of cis-, medial-, and trans-Golgi markers, while the caveolin-1 redistribution resembles that of sec22, a marker for the intermediate compartment. The localization of eNOS and caveolin-1 at distinct perinuclear compartments that behave differently in the presence of nocodazole indicates that eNOS activity is not regulated by caveolin-1 in the Golgi complex.


Dental visits by pediatric HIV-infected medical patients.
The purpose of the study described here was to assess dental-visit frequency in HIV-infected children as reported by caregivers. The sample consisted of 102 HIV-infected children aged 3 to 15 years and their caregivers. The child's most recent visit to any dental clinic for treatment or checkup was reported by the caregiver during his or her monthly medical review. The results were as follows: of the HIV-infected children, 50% had been to the dentist in the past 12 months; an additional 12% had been seen 13 to 36 months prior to the inquiry; and 38% had never visited a dentist. Of children 3 to 7 years old, the figures were 39%, 6% and 55%, respectively. For youth ages 8 to 15 years, figures were 60%, 17% and 23%. Within the racial/ethnic groups, 36% of African-Americans, 41% of Hispanics and 50% of white (non-Hispanic) had never been to a dentist. The researchers believe that the study showed that a significant number of HIV-infected children on public insurance programs receiving consistent medical care had not visited any dental provider.


Granulomatosis with polyangiitis and constrictive pericarditis--a case report.
Polyangiitis with granulomatosis, previously known as Wegener's granulomatosis, is a systemic necrotising granulomatous vasculitis. It predominantly affects the upper and lower respiratory tracts and the kidneys, but can potentially affect any organ system. It is diagnosed by clinical features, immunology (anti-neutrophil cytoplasmic antibodies) and histology. Cardiac involvement occurs in 6 to 44% of cases. We present a case of polyangiitis with granulomatosis and constrictive pericarditis, which occurred despite vigorous immunosuppression and which required surgical pericardectomy.


Cholecystectomy is associated with higher risk of recurrence after microwave ablation of hepatocellular carcinoma: a propensity score matching analysis.
Objective: To explore the association between cholecystectomy and the prognostic outcomes of patients with hepatocellular carcinoma (HCC) who underwent microwave ablation (MWA). Methods: Patients with HCC (n = 921) who underwent MWA were included and divided into cholecystectomy (n = 114) and non-cholecystectomy groups (n = 807). After propensity score matching (PSM) at a 1:2 ratio, overall survival (OS) and disease-free survival (DFS) rates were analyzed to compare prognostic outcomes between the cholecystectomy (n = 114) and non-cholecystectomy groups (n = 228). Univariate and multivariate Cox analyses were performed to assess potential risk factors for OS and DFS. Major complications were also compared between the groups. Results: After matching, no significant differences between groups were observed in baseline characteristics. The 1-, 3-, and 5-year OS rates were 96.5%, 82.1%, and 67.1% in the cholecystectomy group, and 97.4%, 85.2%, and 74.4% in the non-cholecystectomy group (P = 0.396); the 1-, 3-, and 5-year DFS rates were 58.4%, 34.5%, and 26.6% in the cholecystectomy group, and 73.6%, 44.7%, and 32.2% in the non-cholecystectomy group (P = 0.026), respectively. The intrahepatic distant recurrence rate in the cholecystectomy group was significantly higher than that in the non-cholecystectomy group (P = 0.026), and the local tumor recurrence and extrahepatic recurrence rates did not significantly differ between the groups (P = 0.609 and P = 0.879). Multivariate analysis revealed that cholecystectomy (HR = 1.364, 95% CI 1.023-1.819, P = 0.035), number of tumors (2 vs. 1: HR = 2.744, 95% CI 1.925-3.912, P < 0.001; 3 vs. 1: HR = 3.411, 95% CI 2.021-5.759, P < 0.001), and γ-GT levels (HR = 1.003, 95% CI 1.000-1.006, P < 0.024) were independent risk factors for DFS. The best γ-GT level cut-off value for predicting median DFS was 39.6 U/L (area under the curve = 0.600, P < 0.05). A positive correlation was observed between cholecystectomy and γ-GT level (r = 0.108, 95% CI -0.001-0.214, P = 0.047). Subgroup analysis showed that the DFS rates were significantly higher in the non-cholecystectomy group than the cholecystectomy group when γ-GT ≥39.6 U/L (P = 0.044). The 5-, 10-, 15-, 20-, and 25-year recurrence rates from the time of cholecystectomy were 2.63%, 21.93%, 42.11%, 58.77%, and 65.79%, respectively. A significant positive correlation was observed between cholecystectomy and the time from cholecystectomy to recurrence (r = 0.205, 95% CI 0.016-0.379, P = 0.029). There were no significant differences in complications between groups (P = 0.685). Conclusions: Patients with HCC who underwent cholecystectomy were more likely to develop intrahepatic distant recurrence after MWA, an outcome probably associated with increased γ-GT levels. Moreover, the recurrence rates increased with time.


Sensor Type, Axis, and Position-Based Fusion and Feature Selection for Multimodal Human Daily Activity Recognition in Wearable Body Sensor Networks.
This research addresses the challenge of recognizing human daily activities using surface electromyography (sEMG) and wearable inertial sensors. Effective and efficient recognition in this context has emerged as a cornerstone in robust remote health monitoring systems, among other applications. We propose a novel pipeline that can attain state-of-the-art recognition accuracies on a recent-and-standard dataset-the Human Gait Database (HuGaDB). Using wearable gyroscopes, accelerometers, and electromyography sensors placed on the thigh, shin, and foot, we developed an approach that jointly performs sensor fusion and feature selection. Being done jointly, the proposed pipeline empowers the learned model to benefit from the interaction of features that might have been dropped otherwise. Using statistical and time-based features from heterogeneous signals of the aforementioned sensor types, our approach attains a mean accuracy of 99.8%, which is the highest accuracy on HuGaDB in the literature. This research underlines the potential of incorporating EMG signals especially when fusion and selection are done simultaneously. Meanwhile, it is valid even with simple off-the-shelf feature selection methods such the Sequential Feature Selection family of algorithms. Moreover, through extensive simulations, we show that the left thigh is a key placement for attaining high accuracies. With one inertial sensor on that single placement alone, we were able to achieve a mean accuracy of 98.4%. The presented in-depth comparative analysis shows the influence that every sensor type, position, and placement can have on the attained recognition accuracies-a tool that can facilitate the development of robust systems, customized to specific scenarios and real-life applications.


Effect of low-shrinking composite on the bonding effectiveness of two adhesives in occlusal Class-I cavities.
The purpose of this study was to evaluate if a low-shrinking composite can improve the bonding effectiveness of adhesives in highly constrained conditions. A low-shrinking composite ('els-extra low shrinkage', Saremco) was bonded in standardized occlusal Class-I cavities using a three-step ('cmf', Saremco) and a two-step etch-and-rinse adhesive ('XP Bond', Dentsply). Both adhesives were also combined with a conventional composite ('Z100', 3M ESPE). Half of the restored cavities were exposed to 20,000 thermo-cycles. 3-way ANOVA revealed a significant effect for the factors 'adhesive' and 'composite' (both p<0.0001), but not for 'thermo-cycling' (p=0.994). Significantly higher bond strengths were recorded for the low-shrinking composite than for the control composite, using either of the adhesives. The low-shrinking composite in combination with the three-step etch-and-rinse adhesive performed best in the high C-factor Class-I cavity. The two-step etch-and-rinse adhesive suffered strongly from polymerization-shrinkage stress, which could be partially restored by using the low-shrinking composite.


Update on the utilization of grafts in pelvic reconstruction surgeries.
Implanted grafts are increasingly used by pelvic reconstructive surgeons and gynecologists. In addition, the marketing of a variety of grafts has been aggressively expanded without scientific evidence to support their use. This review aims to provide an update of the current status and role of grafts in reconstructive pelvic surgery and to review the current knowledge of the biology of currently marketed synthetic and biologic grafts. Xenografts are preferable to human tissue-banked grafts due to more predictable integrity. How these biomaterials compare to synthetics in terms of surgical outcomes has not been well studied, however. Absorbable materials that mimic some behaviors of synthetic and biological materials have been developed. Furthermore, several new techniques have been advocated with limited studies. While the reduction of surgical failure rates in vaginal surgery is desirable, the addition of graft materials must demonstrate improvement in anatomical, functional, and quality of life outcomes over time. Furthermore, future complications due to improper placement or movement of a graft and the possible shrinkage of the graft are of concern. Therefore, significant research is necessary for the preclinical testing of materials, and expertise needs to be developed for the management of complications.


The diagnosis and treatment of cholangiocarcinoma.
Cholangiocarcinoma (CCA) is the second most common primary hepatic tumor in Germany, with about 3500 new cases per year. In recent years, its prognosis has improved because of wider resections and the establishment of local treatment and chemotherapy in the palliative situation. This review is based on pertinent articles that were retrieved by a selective literature search in the PubMed database with the keywords "cholangiocarcinoma AND diagnostic OR therapy." Articles in English or German published up to January 2014 were considered. The sole curative treatment for CCA is surgery, but 40-85% of all patients have recurrent disease even after radical excision. Because of this high recurrence rate, adjuvant treatments are now under intense discussion. For unresectable CCA without distant metastases, small case series have shown that liver transplantation can yield promising survival rates of over 50% at 5 years. For many patients with CCA, however, only palliative treatments can be offered, including endoscopic clearing of the biliary pathways. Because of the low prevalence of the disease, there have been only a few phase 3 studies of palliative chemotherapy for CCA. On the basis of one positive phase 3 study, chemotherapy with gemcitabine and cisplatin is considered the standard and now plays an established role in palliative care. CCA presents a special challenge in gastroenterology, oncology, and visceral surgery because of the difficulty in establishing the diagnosis, local complications in the biliary pathways, and a high recurrence rate after resection. Future studies should address not only the role of adjuvant chemotherapy, but also the efficacy of combined local and systemic treatment.


Was there really any evidence that rosiglitazone increased the risk of myocardial infarction or death from cardiovascular causes?
Rosiglitazone has previously been widely used to treat patients with type 2 diabetes mellitus, but its safety in terms of cardiovascular morbidity and mortality had been called into question. Recently, there have been doubts raised about the meta-analytic evidence with the regulatory authorities relaxing its restrictions. We hypothesized that the original analyses may have produced exaggerated results because of the small baseline risks involved. To demonstrate this, we replicated the meta-analysis of four randomized trials of greater than 12-month follow-up that made use of a randomized control group not receiving rosiglitazone and reported outcome data for all occurrences of the complementary outcomes (no myocardial infarction, no death from cardiovascular causes, and no heart failure). Data were combined by means of a fixed-effects model. In the rosiglitazone group, as compared with the control group, the relative risk for no myocardial infarction was 0.997 (95% confidence interval [CI], 0.994 to 1.000), and the relative risk for no death from cardiovascular causes was 1.001 (95%CI, 0.999 to 1.003). Finally, no heart failure had a relative risk of 0.995 (95%CI, 0.993 to 0.998). Rosiglitazone does not seem to have any significant increase in the risk of myocardial infarction or of death from cardiovascular causes associated with its use. Regulatory authorities should revisit this issue of the appropriate measure for reporting of adverse events with low baseline risks as this has implications well beyond rosiglitazone.


Extracellular matrix-specific Caveolin-1 phosphorylation on tyrosine 14 is linked to augmented melanoma metastasis but not tumorigenesis.
Caveolin-1 (CAV1) is a scaffolding protein that plays a dual role in cancer. In advanced stages of this disease, CAV1 expression in tumor cells is associated with enhanced metastatic potential, while, at earlier stages, CAV1 functions as a tumor suppressor. We recently implicated CAV1 phosphorylation on tyrosine 14 (Y14) in CAV1-enhanced cell migration. However, the contribution of this modification to the dual role of CAV1 in cancer remained unexplored. Here, we used in vitro [2D and transendothelial cell migration (TEM), invasion] and in vivo (metastasis) assays, as well as genetic and biochemical approaches to address this question in B16F10 murine melanoma cells. CAV1 promoted directional migration on fibronectin or laminin, two abundant lung extracellular matrix (ECM) components, which correlated with enhanced Y14 phosphorylation during spreading. Moreover, CAV1-driven migration, invasion, TEM and metastasis were ablated by expression of the phosphorylation null CAV1(Y14F), but not the phosphorylation mimicking CAV1(Y14E) mutation. Finally, CAV1-enhanced focal adhesion dynamics and surface expression of beta1 integrin were required for CAV1-driven TEM. Importantly, CAV1 function as a tumor suppressor in tumor formation assays was not altered by the Y14F mutation. In conclusion, our results provide critical insight to the mechanisms of CAV1 action during cancer development. Specific ECM-integrin interactions and Y14 phosphorylation are required for CAV1-enhanced melanoma cell migration, invasion and metastasis to the lung. Because Y14F mutation diminishes metastasis without inhibiting the tumor suppressor function of CAV1, Y14 phosphorylation emerges as an attractive therapeutic target to prevent metastasis without altering beneficial traits of CAV1.


Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis -The ANSWER cohort study.
The purpose of this study was to evaluate the retention and discontinuation reasons of seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). 1,037 treatment courses with bDMARDs from 2009 to 2016 [female, 81.8%; baseline age, 59.6 y; disease duration 7.8 y; rheumatoid factor positivity 81.5%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), 4.4; concomitant prednisolone 43.5% and methotrexate 68.6%; Bio-naïve, 57.1%; abatacept (ABT), 21.3%; tocilizumab (TCZ), 20.7%; golimumab (GLM), 16.9%; etanercept (ETN), 13.6%; adalimumab (ADA), 11.1%; infliximab (IFX), 8.5%; certolizumab pegol (CZP), 7.9%] were included in this multi-center, retrospective study. Drug retention and discontinuation reasons at 36 months were estimated using the Kaplan-Meier method and adjusted by potent confounders using Cox proportional hazards modeling. As a result, 455 treatment courses (43.9%) were stopped, with 217 (20.9%) stopping due to inefficacy, 113 (10.9%) due to non-toxic reasons, 86 (8.3%) due to toxic adverse events, and 39 (3.8%) due to remission. Drug retention rates in the adjusted model were as follows: total retention (ABT, 60.7%; ADA, 32.7%; CZP, 43.3%; ETN, 51.9%; GLM, 45.4%; IFX, 31.1%; and TCZ, 59.2%; P < 0.001); inefficacy (ABT, 81.4%; ADA, 65.7%; CZP, 60.7%; ETN, 71.3%; GLM, 68.5%; IFX, 65.0%; and TCZ, 81.4%; P = 0.015), toxic adverse events (ABT, 89.8%; ADA, 80.5%; CZP, 83.9%; ETN, 89.2%; GLM, 85.5%; IFX, 75.6%; and TCZ, 77.2%; P = 0.50), and remission (ABT, 95.5%; ADA, 88.1%; CZP, 91.1%; ETN, 97.5%; GLM, 94.7%; IFX, 86.4%; and TCZ, 98.4%; P < 0.001). In the treatment of RA, ABT and TCZ showed higher overall retention, and TCZ showed lower inefficacy compared to IFX, while IFX showed higher discontinuation due to remission compared to ABT, ETN, GLM, and TCZ in adjusted modeling.


Cardiovascular Disease Update: Care of Patients After Coronary Artery Bypass Graft.
Coronary artery bypass graft (CABG) is a surgical procedure in which a vessel, normally the left internal mammary artery and/or a segment of an excised vein (typically from the leg), is grafted to the coronary arteries to bypass a blockage. CABG has been shown to be superior to percutaneous coronary intervention for patients with complex three vessel disease and left main coronary artery disease. All patients undergoing CABG should receive aspirin preoperatively; they also should receive a beta blocker preoperatively to reduce the likelihood of postsurgical atrial fibrillation. All patients should receive aspirin within 6 hours postsurgery to prevent graft thrombosis and should continue taking aspirin indefinitely, be started or continued on a high-intensity statin, be enrolled in a cardiac rehabilitation program, and be screened and treated if necessary for depression.


Carbamazepine-risperidone interactions in patients with epilepsy.
Because concomitant administration of psychoactive and antiepileptic drugs is increasing progressively in neurologic and psychiatric practice, the aim of the current study was to evaluate the pharmacokinetic interactions between risperidone (RISP) and carbamazepine (CBZ) plasma concentrations in a group of patients with epilepsy with behavioral disturbances. The authors assessed eight patients on CBZ monotherapy (CBZ extended-release capsules) at a mean dosage of 625 +/- 253 mg/day (range, 400-1,200 mg/day) for at least 1 year. RISP (1 mg in one daily dose) was added to CBZ therapy for the occurrence of behavior disturbances. CBZ blood levels were assessed before (T0), 24 hours after (T1), and 2 weeks after (T2) RISP administration. Steady-state plasma concentrations of CBZ increased from 6.67 +/- 0.41 microg/mL at baseline to 7.37 +/- 0.59 microg/mL (p < 0.01) at T1, to 7.95 +/- 0.47 microg/mL (p < 0.0001) at T2. The pharmacokinetic data suggest either a possible role of RISP in inhibiting the cytochrome P450 microsomal enzyme system (CYP)-3A4 pathway or a potential role of CYP2D6 in CBZ metabolism.


Obstructive sleep apnea among patients with retinal vein occlusion.
To evaluate the possible involvement of obstructive sleep apnea (OSA) in retinal vein occlusion (RVO). From the medical records of 63 consecutive patients with RVO, 30 patients with 2 of the 3 following risk factors for OSA were selected for further screening from February 1, 2008, through March 31, 2009: associated cardiovascular disease, snoring, or daytime sleepiness. Of the 30 selected patients, 23 (77%) had OSA. If all 33 of the unscreened patients did not have OSA, the OSA prevalence would have been 37%. Among the patients with OSA, the mean apnea-hypopnea index (AHI) was 21; OSA was mild (AHI <15) in 13 patients, moderate in 5 patients (AHI 15-30), and severe (AHI >30) in 5 patients. The AHI was correlated with body mass index (P = .02). We found a higher than expected prevalence of OSA in a series of patients with RVO. Our findings suggest that OSA could be an additional risk factor that plays an important role in the pathogenesis of RVO or at least that it is a frequently associated condition that could be a triggering factor. This association may explain why most patients discover visual loss on awakening. It is too early to assess whether OSA treatment could improve visual outcome of RVO, but it seems vital to recognize OSA in RVO for the general health of the patient.


Gastrointestinal acute radiation syndrome in Göttingen minipigs (Sus scrofa domestica).
In the absence of supportive care, exposing Göttingen minipigs to γ-radiation doses of less than 2 Gy achieves lethality due to hematopoietic acute radiation syndrome. Doses of 2 to 5 Gy are associated with an accelerated hematopoietic syndrome, characterized by villus blunting and fusion, the beginning of sepsis, and a mild transient reduction in plasma citrulline concentration. We exposed male Göttingen minipigs (age, 5 mo; weight, 9 to 11 kg) to γ-radiation doses of 5 to 12 Gy (total body; (60)Co, 0.6 Gy/min) to test whether these animals exhibit classic gastrointestinal acute radiation syndrome (GI-ARS). After exposure, the minipigs were monitored for 10 d by using clinical signs, CBC counts, and parameters associated with the development of the gastrointestinal syndrome. Göttingen minipigs exposed to γ radiation of 5 to 12 Gy demonstrate a dose-dependent occurrence of all parameters classically associated with acute GI-ARS. These results suggest that Göttingen minipigs may be a suitable model for studying GI-ARS after total body irradiation, but the use of supportive care to extend survival beyond 10 d is recommended. This study is the first step toward determining the feasibility of using Göttingen minipigs in testing the efficacy of candidate drugs for the treatment of GI-ARS after total body irradiation.


A model for regulation of ColE1-like plasmid replication by uncharged tRNAs in amino acid-starved Escherichia coli cells.
It has been previously observed that various ColE1-like plasmids replicate differentially in Escherichia coli cells during the relaxed response to amino acid starvation. Here we develop a kinetic model to explain these observations based on the possibility of interaction of the 3' CCA-OH sequence with the UGG triplets in loops of RNA I and RNA II encoded by ColE1-like plasmids. According to our model, when the interaction of uncharged CCA with RNA I is possible, the replication of the ColE1-like plasmid is affected by differences in the concentration of various tRNAs in the starved cell, but it is not affected by the tRNA concentration if the hypothetical pairing occurs between the CCA-OH and RNA II. Using the previously determined parameters for the pBR322 plasmid, the concentration of uncharged tRNAs in the amino acid starved relaxed strains and the assumed efficiency of binding of tRNA and RNA I, we show that our model explains the differences in pBR322 copy number in the relaxed strain starved for several amino acids.


Immobilization of enzymes using non-ionic colloidal liquid aphrons (CLAs): Surface and enzyme effects.
The use of non-ionic colloidal liquid aphrons (CLAs) as a support for enzyme immobilisation was investigated. Formulation required the mixing of an aqueous-surfactant solution with a relatively non-polar solvent-surfactant solution, forming a solvent droplet surrounded by a thin stabilised aqueous film (soapy shell). Studies utilising anionic surfactants have showed increased retention, however, very little have been understood about the forces governing immobilisation. This study seeks to determine the effects of enzyme properties on CLA immobilisation by examining a non-ionic/non-polar solvent system comprised of two non-ionic surfactants, Tween 20 and 80, mineral oil and the enzymes lipase, aprotinin and α-chymotrypsin. From these results it was deduced that hydrophobic interactions strongly governed immobilisation. Confocal Scanning Laser Microscopy (CSLM) revealed that immobilisation was predominantly achieved by surface adsorption attributed to hydrophobic interactions between the enzyme and the CLA surface. Enzyme surface affinity was found to increase when added directly to the formulation (pre-manufacture addition), as opposed to the bulk continuous phase (post-manufacture addition), with α-chymotrypsin and aprotinin being the most perturbed, while lipase was relatively unaffected. The effect of zeta potential on immobilisation showed that enzymes adsorbed better closer to their pI, indicating that charge minimisation was necessary for immobilisation. Finally, the effect of increasing enzyme concentration in the aqueous phase resulted in an increase in adsorption for all enzymes due to cooperativity between protein molecules, with saturation occurring faster at higher adsorption rates.


Role of protein phosphatases in hypoxic preconditioning.
To find a protein kinase C (PKC)-independent preconditioning mechanism, hypoxic preconditioning (HP; i.e., 10-min anoxia and 10-min reoxygenation) was applied to isolated rat hearts before 60-min global ischemia. HP led to improved recovery of developed pressure and reduced end-diastolic pressure in the left ventricle during reperfusion. Protection was unaffected by the PKC inhibitor bisindolylmaleimide (BIM; 1 micromol/l). It was abolished by the inhibitor of protein phosphatases 1 and 2A cantharidin (20 or 5 micromol/l) and partially enhanced by the inhibitor of protein phosphatase 2A okadaic acid (5 nmol/l). In adult rat cardiomyocytes treated with BIM and exposed to 60-min simulated ischemia (anoxia, extracellular pH 6.4), HP led to attenuation of anoxic Na(+)/Ca(2+) overload and of hypercontracture, which developed on reoxygenation. This protection was prevented by treatment with cantharidin but not with okadaic acid. In conclusion, HP exerts PKC-independent protection on ischemic-reperfused rat hearts and cardiomyocytes. Protein phosphatase 1 seems a mediator of this protective mechanism.


Increased prolyl hydroxylase activity and collagen synthesis in hepatocyte cultures exposed to superoxide.
Primary monolayer cultures of rat hepatocytes at confluence were exposed to an exogenously added source of superoxide, and its influence on collagen synthesis was examined. Superoxide was generated by the addition of dihydroxyfumarate to the culture medium. Exposure of hepatocytes to dihydroxyfumarate greatly stimulated the activity of prolyl hydroxylase and the synthesis of collagen. A significant increase in prolyl hydroxylase activity was observed with 5 micrograms per ml dihydroxyfumarate in 24 hr relative to that in the untreated cultures. Maximum stimulation of greater than 3-fold compared to the control value was elicited by 25 micrograms per ml dihydroxyfumarate. When scavengers of superoxide such as superoxide dismutase and Cu(Lys)2 were added in the medium, the increase in prolyl hydroxylase activity induced by dihydroxyfumarate was nearly abolished. Experiments with actinomycin D indicated that synthesis of new RNA was involved in the stimulation of prolyl hydroxylase activity. Analysis of collagen synthesis in cultures exposed to dihydroxyfumarate also showed a marked increase compared to that of the untreated cultures. The presence of superoxide dismutase in the medium significantly reduced the increase in collagen synthesis. Our results indicate that superoxide mediates the stimulation of collagen synthesis in hepatocytes. These findings may provide a possible explanation for excess collagen formation during induced liver fibrosis.


Retrospective evaluation of pimobendan and sildenafil therapy for severe pulmonary hypertension due to lung disease and hypoxia in 28 dogs (2007-2013).
Pulmonary hypertension (PH) is the persistent abnormal increase in pulmonary artery (PA) pressure and in dogs is usually secondary to congenital disease causing pulmonary over circulation, chronic respiratory disease and elevated left atrial pressure. Sildenafil (SF) is a phosphodiesterase (PDE) V inhibitor that causes pulmonary artery (PA) vasodilation by increasing pulmonary vascular concentrations of cyclic guanosine monophosphate which subsequently increases the activity of endogenous nitric oxide. Pimobendan (PB) is a PDE III inhibitor with calcium sensitizing effects thereby exerting positive inotropy and vasodilation. The purpose of this retrospective study was to evaluate the long-term survival of dogs with severe PH treated with SF and PB compared to SF alone. The use of PB in combination with SF did not result in a statistically significant increase in survival times in dogs with pulmonary hypertension secondary to chronic respiratory disease compared to SF alone.


Morphological Study Of Border Area Of Pulp-Capping Materials And Er:YAG Laser Prepared Hard Dental Surface.
Vital pulp therapy involves biologically based therapeutic activities aimed at restoring health and preserving the vitality of cariously or traumatically damaged pulp. Adaptation of pulp-capping materials to the prepared tooth surface may be the key to the success of biological tooth treatment. To investigate the area of adaptation of synthetic tricalcium silicate cement, calcium hydroxide cement and mineral trioxide-aggregate to the dentin surface, prepared with the help of Er:YAG dental laser. Four extracted human tooth cavities were prepared with the help of Er:YAG dental laser (LiteTouch, Syneron, Israel), establishing microcommunication with the pulp chamber less than 1 mm in diameter. As pulp-capping materials in the cavities we used tricalcium silicate cement (Biodentine, Septodont, France), calcium hydroxide cement (Dycal) and mineral-trioxide aggregate (ProRoot MTA), stirred and administered according to manufacturers' instructions. The first material fills the whole cavity and the other two are spread in a thin layer and sealed with glass ionomer cement. Thus prepared, the samples were left for three days at 37°C in humidified environment. The samples were prepared for scanning electron microscopy (SEM) by standard methodology. The border area surfaces of the materials and the dentin were scanned using electron microscopy. The morphological changes occurring to the Er:YAG laser prepared dentin and the structural characteristics of the studied pulp-capping materials are demonstrated using scanograms. The border areas where good contact of materials and dentinal tubules is established are thoroughly studied. Good adaptation is seen in three-calcium silicate cement, followed by mineral trioxide aggregate and calcium hydroxide cement. The dentin surface, prepared with Er:YAG laser demonstrates a very good adaptation of the three tested pulp-capping materials.


Quantitative Verification of Dynamic Wedge Dose Distribution Using a 2D Ionization Chamber Array.
The accuracy of two calculation algorithms of the Eclipse 8.9 treatment planning system (TPS)--the anisotropic analytic algorithm (AAA) and pencil-beam convolution (PBC)--in modeling the enhanced dynamic wedge (EDW) was investigated. Measurements were carried out for 6 and 18 MV photon beams using a 2D ionization chamber array. Accuracy of the TPS was evaluated using a gamma index analysis with the following acceptance criteria for dose differences (DD) and distance to agreement (DTA): 3%/3 mm and 2%/2 mm. The TPS models the dose distribution accurately except for 20×20 cm(2) field size, 60 (°) and 45 (°) wedge angles using PBC at 6 MV photon energy. For these latter fields, the pass rate and the mean value of gamma were less than 90% and more than 0.5, respectively at the (3%/3 mm) acceptance criteria. In addition, an accuracy level of (2%/2 mm) was achieved using AAA with better agreement for 18 MV photon energy.


Mortality and osteoporotic fractures: is the link causal, and is it modifiable?
Osteoporosis is a global problem with an expected increase in fracture prevalence and public health burden as the world's population ages. Although excess mortality is well-described in those with low bone mineral density as well as those with recent hip and vertebral fractures, some uncertainty remains about whether this link is causal. Survival depends greatly on the fracture types, age, gender, and race. Deaths are predominately due to comorbidities, but may also be attributed to the fracture event itself, either directly or indirectly. The goal of osteoporosis care is prevention of fractures and ultimately reduction in morbidity and mortality. Until recently, there have been no data showing that osteoporosis treatment improves mortality, and even now the extent of these data are rather limited. Large observational cohort studies over considerable time are needed to determine whether improving osteoporosis quality of care will improve mortality rates.


Detection of infectious bursal disease virus in different lymphoid organs by single-step reverse transcription polymerase chain reaction and microplate hybridization assay.
A rapid and sensitive method for the detection of infectious bursal disease virus (IBDV) RNA in different chicken lymphoid organs was developed. The method is based on a single-step reverse transcription polymerase chain reaction (RT-PCR) procedure and the enzyme-linked immunosorbent assay (ELISA) detection method of amplified products. Vaccinal IBDV strain and field isolates were used for the optimization of RT-PCR and for the determination of conditions for microplate hybridization and colorimetric detection of the amplicons. With this method, viral RNA could be detected in various stages of infection in samples of different lymphoid organs. Bursas and cecal tonsils were suitable organs for viral RNA detection at different times during IBDV infection. The RT-PCR/ELISA method can be applied for IBDV detection in routine diagnostic tests, which are not usually carried out because of the difficulties involved in isolating the virus.


Capabilities of the Monte Carlo Simulation Codes for Modeling of a Small Animal SPECT Camera.
This study aims to compare Monte Carlo-based codes' characteristics in the determination of the basic parameters of a high-resolution single photon emission computed tomography (HiReSPECT) scanner. The geometry of this dual-head gamma camera equipped with a pixelated CsI(Na) scintillator and lead hexagonal hole collimator were accurately described in the GEANT4 Application for the Tomographic Emission (GATE), Monte Carlo N-particle extended (MCNP-X), and simulation of imaging nuclear detectors (SIMIND) codes. We implemented simulation procedures similar to the experimental test for calculation of the energy spectra, spatial resolution, and sensitivity of HiReSPECT by using 99mTc sources. The energy resolutions simulated by SIMIND, MCNP-X, and GATE were 17.53, 19.24, and 18.26%, respectively, while it was calculated at 19.15% in experimental test. The average spatial resolutions of the HiReSPECT camera at 2.5 cm from the collimator surface simulated by SIMIND, MCNP-X, and GATE were 3.18, 2.9, and 2.62 mm, respectively, while this parameter was reported at 2.82 mm in the experiment test. The sensitivities simulated by SIMIND, MCNP-X, and GATE were 1.44, 1.27, and 1.38 cps/μCi, respectively, on the collimator surface. Comparison between simulation and experimental results showed that among these MC codes, GATE enabled to accurately model realistic SPECT system and electromagnetic physical processes, but it required more time and hardware facilities to run simulations. SIMIND was the most flexible and user-friendly code to simulate a SPECT camera, but it had limitations in defining the non-conventional imaging device. The most important characteristics like time and speed of simulation, preciseness of results, and user-friendliness should be considered during simulations.


Clinical perspectives on osteogenesis imperfecta versus non-accidental injury.
Although non-accidental injuries (NAI) are more common in cases of unexplained fractures than rare disorders such as osteogenesis imperfecta (OI), ruling out OI and other medical causes of fracture is always indicated. The majority of OI patients can be diagnosed with the help of family history, physical examination, and radiographic findings. In particular, there are a few radiological findings which are seen more commonly in NAI than in OI which may help guide clinician considerations regarding the probability of either of these diagnoses. At the same time, molecular testing still merits careful consideration in cases with unexplained fractures without obvious additional signs of abuse.


Health and medication information resources on the World Wide Web.
Health care practitioners have increasingly used the Internet to obtain health and medication information. The vast number of Internet Web sites providing such information and concerns with their reliability makes it essential for users to carefully select and evaluate Web sites prior to use. To this end, this article reviews the general principles to consider in this process. Moreover, as cost may limit access to subscription-based health and medication information resources with established reputability, freely accessible online resources that may serve as an invaluable addition to one's reference collection are highlighted. These include government- and organization-sponsored resources (eg, US Food and Drug Administration Web site and the American Society of Health-System Pharmacists' Drug Shortage Resource Center Web site, respectively) as well as commercial Web sites (eg, Medscape, Google Scholar). Familiarity with such online resources can assist health care professionals in their ability to efficiently navigate the Web and may potentially expedite the information gathering and decision-making process, thereby improving patient care.


Oral treprostinil diethanolamine for pulmonary arterial hypertension.
The approval of oral treprostinil is a landmark event in the treatment of pulmonary arterial hypertension. Nineteen years after epoprostenol was approved we now have an oral prostanoid available in the USA. Although the current data in prostanoid naïve patients are unimpressive, emerging data suggest that in carefully selected patients oral treprostinil may be able to replace continuously infused treprostinil; however, many hurdles exist for this new medication including overcoming a complex side effect profile, astronomical cost and perhaps other entrants into the oral prostanoid space.