Characterization of the nuclear- and plastid-encoded secA-homologous genes in the unicellular red alga Cyanidioschyzon merolae.
SecA is an ATP-driven motor for protein translocation in bacteria and plants. Mycobacteria and listeria were recently found to possess two functionally distinct secA genes. In this study, we found that Cyanidioschyzon merolae, a unicellular red alga, possessed two distinct secA-homologous genes; one encoded in the cell nucleus and the other in the plastid genome. We found that the plastid-encoded SecA homolog showed significant ATPase activity at low temperature, and that the ATPase activity of the nuclear-encoded SecA homolog showed significant activity at high temperature. We propose that the two SecA homologs play different roles in protein translocation.


[Diagnosis of tuberculosis by immunocapture of the tuberculous bacillus (using magnetic beads)].
Tuberculosis is worldwide considered as a major health problem with high morbidity and mortality rates. Diagnosis of tuberculosis can be problematic. Microscopy, as the basic diagnostic method, stands inadequately alone due to a low sensitivity, and culture suffers from being time-consuming. A rapid, sensitive and simple diagnostic test, applicable in the field is therefore highly needed. A diagnostic method for the detection of M. tuberculosis by immunocapture technique has been developed using magnetic beads coated with polyclonal anti-M. tuberculosis. The detection of captured bacilli using biotinylated anti-APA monoclonal antibody (APA is a minor secreted antigen) was found more sensitive than microscopy. The results suggest that the development of a rapid strip test to detect major antigen could be a useful tool for the control of tuberculosis.


Visually and posturally mediated tilt illusion in Parkinson's disease and in labyrinthine defective subjects.
We tested 24 normal subjects, 24 patients with idiopathic Parkinson's disease (PD), and eight patients with bilateral absence of vestibular function (labyrinthine defective [LD] subjects) in their ability to set a straight line to the perceived gravitational vertical (visual vertical). Measurements were taken in static conditions, sitting upright, and lying down on the right side, and during visual background motion at constant angular velocities around the line of sight (roll-motion) in both sitting upright and sideways position. Aims of the study were to determine if the reported increased "visual dependence" in PD was present in a psychophysical task that is independent of motor performance, and to examine the interaction between visual motion and proprioceptive cues in the perception of verticality, in the absence of vestibular function. LD patients showed abnormally large deviations of the visual vertical induced both by lateral body tilt and by visual roll-motion. This suggests that vestibular cues play a significant part in counterbalancing visually and proprioceptive mediated biases on the perception of verticality. In contrast, PD patients were normal in all these tasks indicating that visual dependence in PD is not present at an afferent/perceptual level.


Holographic patient tracking after bed movement for augmented reality neuronavigation using a head-mounted display.
Holographic neuronavigation has several potential advantages compared to conventional neuronavigation systems. We present the first report of a holographic neuronavigation system with patient-to-image registration and patient tracking with a reference array using an augmented reality head-mounted display (AR-HMD). Three patients undergoing an intracranial neurosurgical procedure were included in this pilot study. The relevant anatomy was first segmented in 3D and then uploaded as holographic scene in our custom neuronavigation software. Registration was performed using point-based matching using anatomical landmarks. We measured the fiducial registration error (FRE) as the outcome measure for registration accuracy. A custom-made reference array with QR codes was integrated in the neurosurgical setup and used for patient tracking after bed movement. Six registrations were performed with a mean FRE of 8.5 mm. Patient tracking was achieved with no visual difference between the registration before and after movement. This first report shows a proof of principle of intraoperative patient tracking using a standalone holographic neuronavigation system. The navigation accuracy should be further optimized to be clinically applicable. However, it is likely that this technology will be incorporated in future neurosurgical workflows because the system improves spatial anatomical understanding for the surgeon.


KL-6, a human MUC1 mucin, is chemotactic for human fibroblasts.
KL-6 in serum and bronchoalveolar lavage fluid has been reported to be a sensitive marker indicating the activity of fibrosing lung diseases. The molecule is clustered in MUC1 mucin according to the findings of immunohistochemical and cytometric studies. To elucidate the pathogenic role of KL-6 in fibrosing lung disease, we characterized its biochemical properties and examined whether purified KL-6 is chemotactic for human fibroblasts in vitro using modified Boyden chambers. Biochemical properties of purified KL-6 were similar to those of other MUC1 mucins previously reported. KL-6 promoted the migration of 5 of 5 human lung fibroblasts and 3 of 4 human skin fibroblasts. Checkerboard analysis revealed that KL-6 was chemotactic as well as chemokinetic. Though platelet-derived growth factor, fibroblast growth factor, or fibronectin were also chemotactic for fibroblasts in the experimental system, only fibronectin augmented KL-6-induced chemotaxis. These observations indicate that KL-6 is one of the chemotactic factors for most fibroblasts and that the increased KL-6 in the epithelial lining fluid in small airways may cause the intra-alveolar fibrosis in fibrosing lung diseases.


[Physical factors of the industrial environment and traffic safety].
The paper deals with the problem of optimization of working conditions of engine drivers in the control cabs of up-to-date locomotives, by toughening the sanitary-and-hygienic requirements for the levels of bad industrial factors. The authors associate the optimization of working conditions with the necessity of strengthening the reliability of their driving activity due to the increasing rail movement speeds and the transfer to one-person rolling-stock operation, and other factors.


Optical Evaluation of the Surface Coverage of Silver Nanoparticle-coated Plastic Microbeads.
A simple evaluation method has been developed for a metal thin layer on a sphere-like plastic microstructure, based on its light-scattering property since, according to our results, the light-scattering intensity of silver-coated microbeads depends significantly on the silver coverage. Our attempt was carried out by using a dark-field microscopy coupled with a spectrometer.


Father surrogate: historical perceptions and perspectives of men in nursing and their relationship with fathers in the NICU.
Femininity is often associated with the nursing profession, but is not one of its defining characteristics. Men have been providing care to the sick and injured for many centuries, and they continue to do so for many reasons. Male nurses display a wide range of caring practices, which may not always be interpreted as such by their female counterparts. This article presents the male perspective and approach to caring, including the unique relationship that male nurses can have with fathers in the NICU.


Antiphospholipid antibodies and thrombosis. A consequence, coincidence, or cause?
Antiphospholipid antibodies have been identified as a potential risk factor for both arterial and venous thromboembolic events. Whether these antibodies are causative or a consequence of a previous clinical event remains controversial. A variety of laboratory assays have been introduced to detect the two primary members of the antiphospholipid antibody family: (1) lupus anticoagulants and (2) anticardiolipin antibodies. There is considerable variability in the laboratory tests that have been utilized. A number of potential pathogenic mechanisms have been proposed for antiphospholipid antibodies. These mechanisms involve the interaction of antiphospholipid antibodies with endothelial cells, platelets, and various plasma regulatory proteins. Although venous thromboembolic events are more common, recent evidence suggests a high frequency of arterial events. The cerebral circulation is most commonly involved, followed by involvement of the coronary arteries. An interesting subset of young patients have peripheral vascular disease that often is relatively refractory to surgical treatment with a high incidence of graft occlusion.


Thymus Vulgaris Inhibit Lung Fibrosis Progression and Oxidative Stress Induced by Bleomycin in Wistar Rats.
Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating and fatal disease characterized by aberrant fibroblasts proliferation, oxidative stress and collagen accumulation in the interstitial tissue. We aimed to evaluate in the present study the efficacy of Thymus vulagris extract (TVE) on an experimental model of pulmonary fibrosis induced by bleomycin (BLM). Wistar rats were given a single dose of BLM (4 mg/kg, intratracheal), while TVE (50, 100 and 200 mg/kg, intraperitoneal) was administered 3 days later and continued for 4 weeks. We reveled by HPLC analysis an important amount of phenolic bioactive compounds such as rosmarinic and vanillic acids. Our results showed a significant decrease of catalase and superoxide dismutase activities and an increase in lipid peroxidation compared to control group after BLM injection. Treatment with TVE (200 mg/kg) was able to normalize the level of these oxidative markers and to decrease collagen accumulation compared to BLM group. Moreover, this high dose of TVE have no renal or hepatic cytotoxic effects. This study allowed us to conclude that thyme extract has a strong antioxidant and antifibrotic activities due to its high content of polyphenols.


Rapid Microbiological Assessment in Raw Milk: Validation of a Rapid Alternative Method for the Assessment of Microbiological Quality in Raw Milk.
The consumption of dairy products and the dairy industry are one of the main global agri-food sectors for its size, economic importance, and level of technology. Microbiological quality of pasteurized milk or other milk products is dependent on microbiological quality of raw milk. A variety of microbiological count methods is available for monitoring the hygienic quality of raw milk. Among them, the pour plate method is the official essay for counting the number of colony-forming units in milk samples according to International Organization for Standardization (ISO) No. 4833-1:2013. The aim of the present study is the validation of the Micro Biological Survey (MBS) method, against the reference plate-count method, for the assessment of the microbiological quality of raw milk. This comparative study, performed in collaboration with the Istituto Zooprofilattico Sperimentale del Lazio e della Toscana M. Aleandri (IZSLT), demonstrates the accuracy of this alternative method for the determination of total viable bacterial count in cow's raw milk. The results obtained with the MBS method highlight its potential as a valid tool for reliable microbiological analysis in dairy industries.


Herpes simplex virus type 2 UL14 gene product has heat shock protein (HSP)-like functions.
The HSV-2 UL14 gene encodes a 32 kDa protein that is a minor component of the viral tegument. The protein relocates other viral proteins such as VP26 and UL33 protein into the nuclei of transiently coexpressing cells (Yamauchi et al., 2001). We found that the protein shared some characteristics of heat shock proteins (HSPs) or molecular chaperones, such as nuclear translocation upon heat shock, ATP deprivation and osmotic shock. Interestingly, a significant homology over a stretch of 15 amino acids was found between an N-terminal region of HSV UL14 protein and the substrate-binding domain of Hsp70 family proteins. Two arginine residues in this region were important for nuclear translocation of VP26. In addition, overexpression of UL14 protein increased the activity of coexpressed firefly luciferase, which suggested that the protein functioned in the folding of newly synthesized luciferase. We thus conclude that UL14 protein can act as a chaperone-like protein in a singly expressed state.


[Hematopoietic stem cells (CFU-S) in retrovirus-induced murine malignant histiocytosis].
The murine malignant histiocytosis sarcoma virus (MHSV) is a replication-defective murine retrovirus which contains a ras-oncogen. Upon intravenous infection of normal adult NIH-mice a rapidly fatal systemic proliferation of transformed mononuclear phagocytes develops. We have investigated the involvement of other mature hematopoietic lineages and of hematopoietic stem cells during the course of the disease. The erythroid lineage is affected by a profound anemia which is temporarily accompanied by an increase of erythroid precursors in bone marrow and spleen and a final ablation of erythroid stem cells. A granulopenia occurs with a concurrent decrease of granulocytic precursors and stem cells. The platelets fall to very low levels early during the disease despite of an increase of megakaryocytes and megakaryocytic stem cells. Multipotential stem cells show temporarily a slight increase followed by an almost total terminal ablation. The results show that MHSV has distinct effects on other hematopoietic lineages apart from its transforming properties.


[Outcome of herpetic encephalitis. Apropos of 10 cases].
Ten cases of herpetic encephalitis in children aged 2 months to 13 1/2 years at onset are reviewed retrospectively. There were four infants and six children 3 to 13 1/2 years old. Diagnosis was established on the basis of widely accepted electroclincal and neuroradiological criteria. Biologic confirmation was obtained in only half the cases. Two patients died during the initial episode. One patient was lost to follow-up two months after the first episode. Follow-ups ranged from 2 to 10 years for the seven remaining patients. Epilepsy and neurodevelopmental impairment occurred in a significant number of cases (5/7 and 6/7 respectively). Two patients had two episodes and one had more than two episodes of encephalitis. This poor outcome is discussed, as well as possible explanations for recurrent disease and particular neuropsychologic patterns, including Kluver-Bucy syndrome seen in two patients of this series.


In vitro activity of lomefloxacin, a difluorinated quinolone, compared with other antimicrobials.
A total of 3,144 clinical isolates from 3,011 consecutive patients were tested against lomefloxacin by the agar dilution method. They consisted of 1,380 isolates of Enterobacteriaceae, 527 pseudomonads, 47 Haemophilus influenzae, 53 Acinetobacter, 42 Brucella melitensis, 903 staphylococci and 192 strains of enterococci. In vitro activity of lomefloxacin was compared with ciprofloxacin, norfloxacin, beta-lactams and aminoglycosides. Over 98% of Enterobacteriaceae were susceptible to lomefloxacin with an MIC of 0.06-4.0 micrograms/ml. It also inhibited 93 and 85% clinical isolates of Pseudomonas aeruginosa and Xanthomonas maltophilia, respectively. All isolates of Haemophilus, Brucella and Staphylococcus aureus were susceptible to this fluoroquinolone. However, only 43% of the 192 strains of enterococci exhibited in vitro susceptibility. Lomefloxacin was found to be comparable to ciprofloxacin and norfloxacin in its in vitro activity, and superior to most penicillins, cephalosporins and aminoglycosides against both gram-negative and gram-positive bacteria except enterococci.


Basic fibroblast growth factor increases regional cerebral blood flow and reduces infarct size after experimental ischemia in a rat model.
The aim of this study was to ascertain whether basic fibroblast growth factors (bFGF) caused reduction in size of cerebral infarcts in Sprague-Dawley rats with experimental ischemia. In the first experiment we induced permanent occlusion of the left middle cerebral artery (MCA). Within 5 minutes after MCA occlusion, we infused bFGF (100 ng in 0.1 mL of saline) in the bFGF-treated group (n = 14) and 0.1 mL of saline alone in the control group (n = 7) into the common carotid artery ipsilateral to MCA occlusion. We harvested the brains 24 hours after MCA occlusion and determined infarct size planimetrically as a percentage of hemisphere size. In the second experiment cerebral blood flow (CBF) was continuously measured for 120 minutes after MCA occlusion in the bFGF-treated group (n = 9) and in the control group (n = 8) with the use of laser-Doppler flowmetry. Infarct size in the bFGF-treated group decreased significantly in comparison with that in the control group (repeated-measures ANOVA, P < .0001). CBF in the transitional areas between the MCA and the anterior cerebral artery significantly increased in the bFGF-treated group in comparison with that in the control group (repeated-measures ANOVA, P < .005). An approximate 58% decrease in infarct size and a 40% increase in regional CBF were seen on bFGF treatment. The present study suggested that intracarotid administration of bFGF (100 ng) can reduce infarct size after MCA occlusion. It was speculated that the increased CBF in the penumbral areas of MCA may contribute to contraction of infarct size.


Involvement of p21waf1/cip1 expression in the cytotoxicity of the potent histone deacetylase inhibitor spiruchostatin B towards susceptible NALM-6 human B cell leukemia cells.
Spiruchostatin B (SP-B) is a potent histone deacetylase (HDAC) inhibitor that has potential for the chemotherapy of leukemia. The aim of this study was to study the susceptibility of human leukemia cell lines to SP-B. We found that NALM-6 human B cell leukemia cells are the most susceptible to SP-B. There was a low correlation between the expression of HDAC1 mRNA and HDI susceptibility of leukemia cells. NALM-6 has higher endogenous p21waf1/cip1 mRNA expression than other leukemia cells. SP-B-induced cytotoxicity was mediated by induction of histone acetylation via inhibition of HDACs, and this effect of SP-B was associated with apoptosis, which was mediated by caspase activation in NALM-6 cells. SP-B time-dependently increased the size of the sub-G1 (apoptotic) peak, and this effect correlated with SP-B induction of cellular apoptotic features such as changes in nuclear morphology. SP-B significantly increased p21waf1/cip1 expression prior to induction of apoptosis. In conclusion, NALM-6 cells, which have a higher expression of p21waf1/cip1 mRNA than other leukemia cell lines, were susceptible to SP-B-induced cytotoxicity that resulted in induction of apoptosis. Our findings may be useful when establishing a therapeutic strategy based on SP-B.


Phagocytosis of IgG-coated polystyrene beads by macrophages induces and requires high membrane order.
The biochemical composition and biophysical properties of cell membranes are hypothesized to affect cellular processes such as phagocytosis. Here, we examined the plasma membranes of murine macrophage cell lines during the early stages of uptake of immunoglobulin G (IgG)-coated polystyrene particles. We found that the plasma membrane undergoes rapid actin-independent condensation to form highly ordered phagosomal membranes, the biophysical hallmark of lipid rafts. Surprisingly, these membranes are depleted of cholesterol and enriched in sphingomyelin and ceramide. Inhibition of sphingomyelinase activity impairs membrane condensation, F-actin accumulation at phagocytic cups and particle uptake. Switching phagosomal membranes to a cholesterol-rich environment had no effect on membrane condensation and the rate of phagocytosis. In contrast, preventing membrane condensation with the oxysterol 7-ketocholesterol, even in the presence of ceramide, blocked F-actin dissociation from nascent phagosomes and particle uptake. In conclusion, our results suggest that ordered membranes function to co-ordinate F-actin remodelling and that the biophysical properties of phagosomal membranes are essential for phagocytosis.


DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients.
Aberrant DNA methylation of tumor suppressor genes has been reported in all major types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. However, most of the previous reports did not show the extent of concurrent methylation of multiple genes in the four leukemia types. Here, we analyzed six key genes (p14, p15, p16, p53, DAPK and TMS1) for DNA methylation using methylation specific PCR to analyze peripheral blood of 78 leukemia patients (24 CML, 25 CLL, 12 AML, and 17 ALL) and 24 healthy volunteers. In CML, methylation was detected for p15 (11%), p16 (9%), p53 (23%) and DAPK (23%), in CLL, p14 (25%), p15 (19%), p16 (12%), p53 (17%) and DAPK (36%), in AML, p14 (8%), p15 (45%), p53 (9%) and DAPK (17%) and in ALL, p15 (14%), p16 (8%), and p53 (8%). This study highlighted an essential role of DAPK methylation in chronic leukemia in contrast to p15 methylation in the acute cases, whereas TMS1 hypermethylation was absent in all cases. Furthermore, hypermethylation of multiple genes per patient was observed, with obvious selectiveness in the 9p21 chromosomal region genes (p14, p15 and p16). Interestingly, methylation of p15 increased the risk of methylation in p53, and vice versa, by five folds (p=0.03) indicating possible synergistic epigenetic disruption of different phases of the cell cycle or between the cell cycle and apoptosis. The investigation of multiple relationships between methylated genes might shed light on tumor specific inactivation of the cell cycle and apoptotic pathways.


Vascular permeability during the early and late phases of ocular anaphylaxis.
The role of enhanced vascular permeability in a model of ocular anaphylaxis was investigated during both early- and late-phase reactions (EPR and LPR). Vascular permeability was assessed by measuring the extravascular retention of 125I-bovine serum albumin (125I-BSA) in ocular tissues. Ten groups of guinea pigs (n = 5-12 per group) were injected with dinitrophenylated (DNP) bovine gamma globulin emulsified in Freund's adjuvants and challenged after a 4-week interval by topical application of di-DNP-lysine to one eye and phosphate-buffered saline to the other eye. Thereafter, the eyes were examined and the animals were killed at different intervals after topical challenge. They were injected intravenously with 125I-BSA 0.5 hr before death. Retained radioactivity was measured separately in four tissues. The EPR (period between 0.5-1.5 hr after challenge) was characterized by enhanced retention of radioactivity in lids, conjunctiva, and orbital content. There was no significant retention of extravascular radioactivity in the globe and lacrimal gland. Thereafter (period between 2-3.5 hr after challenge), retained radioactivity was significantly diminished. The subsequent period, between 4.5-6.5 hr (LPR), was characterized by a smaller, although significant, increment of radioactivity retained in lids and conjunctiva but not in the other tissues examined. These findings indicate that enhanced microvascular permeability occurs during two phases in actively immunized guinea pigs challenged topically with di-DNP-lysine and that these phases correspond to the clinical signs that constitute the EPR and LPR of ocular anaphylaxis.


An analysis of sequential physiologic changes in hypoxic cor pulmonale during long-term oxygen therapy.
Physiologic changes were studied retrospectively in 37 patients with hypoxic cor pulmonale who died during long-term oxygen therapy (LTOT). The subjects were assessed during periods of clinical stability for each year on LTOT. At the onset of treatment, their mean age (+/- SEM) was 60.0 +/- 1.3 years, and at the time of death, they were aged 65.0 +/- 1.3 years. The median duration of LTOT was five years. For each year leading up to death, mean values of FEV1, PaO2, and PaCO2 were obtained. A rate of decline of FEV1 of 73 +/- 10 ml/yr was observed, and this was accompanied by a decline in PaO2 of 0.47 +/- 0.01 kPa/yr. Patients died with a mean FEV1 of 0.55 +/- 0.04 L and a PaO2 of 5.1 +/- 0.2 kPa. A small rise in PaCO2 occurred, on average 0.25 +/- 0.09 kPa/yr, throughout the study, but accelerating in many cases during the three years before death. Hypoxic cor pulmonale appears to be associated with a rapid deterioration in airway function, a steady decline in PaO2, and a slow rise in PaCO2 during the years leading up to death. These physiologic changes measured in a stable clinical state while breathing air appear to occur in spite of LTOT. The LTOT may merely prevent death from episodes of severe hypoxemia while the pathophysiologic changes in the lung progress. Hence the benefit to be expected from LTOT is only temporary. Generally, those patients with lower levels of FEV1 will obtain diminishing clinical benefit, inversely related to the severity of airflow obstruction at the time of commencement of LTOT.


A mutant in the ADH1 gene of Chlamydomonas reinhardtii elicits metabolic restructuring during anaerobiosis.
The green alga Chlamydomonas reinhardtii has numerous genes encoding enzymes that function in fermentative pathways. Among these, the bifunctional alcohol/acetaldehyde dehydrogenase (ADH1), highly homologous to the Escherichia coli AdhE enzyme, is proposed to be a key component of fermentative metabolism. To investigate the physiological role of ADH1 in dark anoxic metabolism, a Chlamydomonas adh1 mutant was generated. We detected no ethanol synthesis in this mutant when it was placed under anoxia; the two other ADH homologs encoded on the Chlamydomonas genome do not appear to participate in ethanol production under our experimental conditions. Pyruvate formate lyase, acetate kinase, and hydrogenase protein levels were similar in wild-type cells and the adh1 mutant, while the mutant had significantly more pyruvate:ferredoxin oxidoreductase. Furthermore, a marked change in metabolite levels (in addition to ethanol) synthesized by the mutant under anoxic conditions was observed; formate levels were reduced, acetate levels were elevated, and the production of CO(2) was significantly reduced, but fermentative H(2) production was unchanged relative to wild-type cells. Of particular interest is the finding that the mutant accumulates high levels of extracellular glycerol, which requires NADH as a substrate for its synthesis. Lactate production is also increased slightly in the mutant relative to the control strain. These findings demonstrate a restructuring of fermentative metabolism in the adh1 mutant in a way that sustains the recycling (oxidation) of NADH and the survival of the mutant (similar to wild-type cell survival) during dark anoxic growth.


Rapid Identification and Assignation of the Active Ingredients in Fufang Banbianlian Injection Using HPLC-DAD-ESI-IT-TOF-MS.
Fufang Banbianlian Injection (FBI) is a well-known traditional Chinese medicine formula composed of three herbal medicines. However, the systematic investigation on its chemical components has not been reported yet. In this study, a high-performance liquid chromatography combined with diode-array detector, and coupled to an electrospray ionization with ion-trap time-of-flight mass spectrometry (HPLC-DAD-ESI-IT-TOF-MS) method, was established for the identification of chemical profile in FBI. Sixty-six major constituents (14 phenolic acids, 14 iridoids, 20 flavonoids, 2 benzylideneacetone compounds, 3 phenylethanoid glycosides, 1 coumarin, 1 lignan, 3 nucleosides, 1 amino acids, 1 monosaccharides, 2 oligosaccharides, 3 alduronic acids and citric acid) were identified or tentatively characterized by comparing their retention times and MS spectra with those of standards or literature data. Finally, all constituents were further assigned in the individual herbs (InHs), although some of them were from multiple InHs. As a result, 11 compounds were from Lobelia chinensis Lour, 33 compounds were from Scutellaria barbata D. Don and 38 compounds were from Hedyotis diffusa Willd. In conclusion, the developed HPLC-DAD-ESI-IT-TOF-MS method is a rapid and efficient technique for analysis of FBI sample, and could be a valuable method for the further study on the quality control of the FBI.


PDK2-enhanced glycolysis promotes fibroblast proliferation in thyroid-associated ophthalmopathy.
The study aimed to investigate the role of pyruvate dehydrogenase kinase (PDK) in regulating glycolysis and proliferation of perimysial orbital fibroblasts (pOFs) during the pathogenesis of thyroid-associated ophthalmopathy (TAO). EdU and BrdU incorporation assays were performed to examine cell proliferation. Lactate production and oxygen consumption assays were conducted to evaluate glycolysis. Real-time PCR was adapted to quantify PDK mRNA levels. Capillary Western immunoassay was adapted to quantify PDK2, Akt, pAkt308 and GAPDH in protein samples. The TAO pOFs exhibited stronger proliferation activity, higher intracellular lactate concentration, and lower oxygen consumption rate than the control pOFs. The PDK inhibitor dichloroacetic acid (DCA) dose-dependently suppressed the proliferation of both TAO and control pOFs. DCA reduced lactate production and promoted oxygen consumption in the TAO pOFs but showed no significant effects on glycolysis in the control pOFs. Among four PDK isotypes, PDK2 was overexpressed in the TAO pOFs. The potential PDK signaling mediator, cytoplasmic Akt, was more abundant in TAO pOFs than control pOFs. Knockdown of PDK2 resulted in lower lactate production, stronger oxygen consumption, weaker proliferation activity, and less cytoplasmic Akt in the TAO pOFs but showed no significant effects in the control pOFs. The Akt inhibitor MK2206 suppressed proliferation in both TAO and control pOFs, and lactate production was inhibited by MK2206 in the TAO OFs but not the control pOFs. To conclude, PDK2 overexpression enhances glycolysis and promotes proliferation via Akt signaling in the TAO pOFs. These findings yield insights that PDK2 is a potential therapeutic target for TAO treatment.


The Effect of Time Spent with a Dynamic Spacer on Clinical and Functional Outcomes in Two-Stage Revision Knee Arthroplasty.
The present study aimed to evaluate the effect of a longer interval between the first and second stages of infected total knee arthroplasty (TKA) revision on the clinical and functional outcome. This study included a total of 56 patients who underwent two-stage revision TKA with a dynamic spacer with a minimum of 2 years of follow-up. Patients were categorized into two groups according to time with the spacer: < 3 months (Group 1, 31 patients) or > 3 months (Group 2, 25 patients). Clinical outcome and quality of life were assessed by knee range of motion (ROM), Knee Society Score for Knee (KSS-K), Knee Society Score for Function (KSS-F) and Short Form 36 (SF-36). The mean follow-up period was 48 ± 19.1 months (range, 24-84 months). The KSS-K, KSS-F, and ROM values were significantly higher in Group 1 than in Group 2 (p < 0.05). The SF-36 scores for general health, physical function, and bodily pain were significantly higher in Group 1 (p < 0.05). Re-infection occurred in 10 patients (17.8%). Time with spacer was not associated with re-infection development (Group 1, n = 6, 19% vs. Group 2, n = 4, 16%; p > 0.05). Increased duration with a spacer is associated with poorer clinical and functional outcomes as well as higher treatment costs in two-stage revision knee arthroplasty. Surgeons can attempt to reduce the time patients spend in a spacer to obtain better postoperative functional outcomes, as well as a better quality of life. 3.


Bones as biofuel: a review of whale bone composition with implications for deep-sea biology and palaeoanthropology.
Whales are unique among vertebrates because of the enormous oil reserves held in their soft tissue and bone. These 'biofuel' stores have been used by humans from prehistoric times to more recent industrial-scale whaling. Deep-sea biologists have now discovered that the oily bones of dead whales on the seabed are also used by specialist and generalist scavenging communities, including many unique organisms recently described as new to science. In the context of both cetacean and deep-sea invertebrate biology, we review scientific knowledge on the oil content of bone from several of the great whale species: Balaenoptera musculus, Balaenoptera physalus, Balaenoptera borealis, Megaptera novaeangliae, Eschrichtius robustus, Physeter macrocephalus and the striped dolphin, Stenella coeruleoalba. We show that data collected by scientists over 50 years ago during the heyday of industrial whaling explain several interesting phenomena with regard to the decay of whale remains. Variations in the lipid content of bones from different parts of a whale correspond closely with recently observed differences in the taphonomy of deep-sea whale carcasses and observed biases in the frequency of whale bones at archaeological sites.


Diagnosis of hemochromatosis.
Hereditary hemochromatosis is an inherited disorder of iron metabolism affecting approximately 1 in 200 to 300 individuals of Northern European descent. Over time, the continued deposition of iron in parenchymal cells of many organs can eventually lead to diabetes mellitus, cardiomyopathy, and hepatic cirrhosis, the last of which is frequently followed by hepatocellular carcinoma. Although the complications of hereditary hemochromatosis can be devastating, its clinical management is simple and effective if the disease is identified early in its progression. In affected individuals, it is important to confirm or exclude the presence of cirrhosis and begin therapy as early as possible. The insidious onset and high prevalence of nonspecific symptoms in the early stages of the disease requires the clinician to have a high index of clinical suspicion for this disease. This is particularly important because treatment before there is permanent organ damage can reverse the iron toxicity and restore life expectancy to normal. Because of its familial occurrence all first-degree relatives of patients with hereditary hemochromatosis should be tested for the disease.


Toward an implicit measure of emotions: ratings of abstract images reveal distinct emotional states.
Although implicit tests of positive and negative affect exist, implicit measures of distinct emotional states are scarce. Three experiments examined whether a novel implicit emotion-assessment task, the rating of emotion expressed in abstract images, would reveal distinct emotional states. In Experiment 1, participants exposed to a sadness-inducing story inferred more sadness, and less happiness, in abstract images. In Experiment 2, an anger-provoking interaction increased anger ratings. In Experiment 3, compared to neutral images, spider images increased fear ratings in spider-fearful participants but not in controls. In each experiment, the implicit task indicated elevated levels of the target emotion and did not indicate elevated levels of non-target negative emotions; the task thus differentiated among emotional states of the same valence. Correlations also supported the convergent and discriminant validity of the implicit task. Supporting the possibility that heuristic processes underlie the ratings, group differences were stronger among those who responded relatively quickly.


Osteoprotegerin genetic polymorphisms and age of symptom onset in ankylosing spondylitis.
Osteoporosis is one of the recognized features of AS. It is known that RANK ligand (RANKL), which binds to RANK, can cause the activation of bone resorption. Osteoprotegerin (OPG) also competes with RANK by binding to RANKL and inhibiting bone absorption. Therefore, we designed a case-control study to evaluate the association between occurrence and clinical features of AS and RANK, RANKL and OPG genetic polymorphisms. A total of 330 AS patients and 330 age- and gender-matched controls were recruited. PCR-restriction fragment length polymorphism was applied to identify RANK C575T, RANKL C-290T and OPG G1181C genotypes. OPG GG genotype carriers had an elevated risk of AS compared with those with the GC and CC genotypes (matched odds ratio 1.74; 95% CI 1.26, 2.40). Age of symptom onset and frequency of peripheral arthritis significantly differed among AS patients by OPG G1181C genotypes. HLA-B27(+) patients with the OPG C allele had the earliest age of symptom onset [mean (s.d.) 26.6 (9.6) years], followed by HLA-B27(+) patients with the OPG G allele [32.6 (12.2) years], HLA-B27(-) patients with the OPG G allele [38.1 (13.6) years] and HLA-B27(-) patients with the OPG C allele [38.6 (9.8) years]. CONCLUSION. OPG G1181C polymorphism may be associated with AS development and clinical manifestations.


Ileus in the newborn: a study of decreasing mortality.
The authors' experience with operative therapy for ileus-duodenal, small intestinal, colon, and rectal-in newborns is presented with an analysis of the improvements in prognosis over the last 30 years. For the time period 1980-1989, the following survival rates were achieved: duodenum: 100%; small bowel: overall 96.8%, for uncomplicated cases 100%; congenital megacolon: overall 89%, for uncomplicated cases 100%; ileus of all intestinal portions together: 97.5%, for uncomplicated cases 100%.


[An analysis of combined desensitizing acupoints therapy in 419 cases of allergic rhinitis accompanying asthma].
To explore the effective therapy in treating allergic rhinitis accompanying asthma. A combined desensitizing therapy in treating 419 cases of allergic rhinitis accompanying asthma caused by allergens has been carried out using acupoint of the head and the upper back with the extract of positive allergen(s). After three treatment courses, the extract of allergens was taken again to make intradermal injection. Diameter of redness and swelling on the skin was significantly reduced in comparison with that before the treatment (P < 0.01). Lymphocyte transformation difference of 3H-TdR incorporation rate between a combined desensitizing acupoints group and A or B control groups was significant (P < 0.01). Difference of acidophil cell direct count, IgA, IgG, E-rosette formative rate of this group in comparison with A or B control groups was significant (P < 0.05). Four hundred and nineteen cases were followed up for 3 years, 68.73% of the patients were markedly curative effect; 29.12% turned better. Comparison of the difference of this group with the other two control groups was significant (P < 0.01). This article showed that the method is promising and worthwhile for popularizing in treatment of allergic rhinitis accompanying allergic asthma.


EmrR-Dependent Upregulation of the Efflux Pump EmrCAB Contributes to Antibiotic Resistance in Chromobacterium violaceum.
Chromobacterium violaceum is an environmental Gram-negative bacterium that causes infections in humans. Treatment of C. violaceum infections is difficult and little is known about the mechanisms of antibiotic resistance in this bacterium. In this work, we identified mutations in the MarR family transcription factor EmrR and in the protein GyrA as key determinants of quinolone resistance in C. violaceum, and we defined EmrR as a repressor of the MFS-type efflux pump EmrCAB. Null deletion of emrR caused increased resistance to nalidixic acid, but not to other quinolones or antibiotics of different classes. Moreover, the ΔemrR mutant showed decreased production of the purple pigment violacein. Importantly, we isolated C. violaceum spontaneous nalidixic acid-resistant mutants with a point mutation in the DNA-binding domain of EmrR (R92H), with antibiotic resistance profile similar to that of the ΔemrR mutant. Other spontaneous mutants with high MIC values for nalidixic acid and increased resistance to fluoroquinolones presented point mutations in the gene gyrA. Using DNA microarray, Northern blot and EMSA assays, we demonstrated that EmrR represses directly a few dozen genes, including the emrCAB operon and other genes related to transport, oxidative stress and virulence. This EmrR repression on emrCAB was relieved by salicylate. Although mutation of the C. violaceum emrCAB operon had no effect in antibiotic susceptibility or violacein production, deletion of emrCAB in an emrR mutant background restored antibiotic susceptibility and violacein production in the ΔemrR mutant. Using a biosensor reporter strain, we demonstrated that the lack of pigment production in ΔemrR correlates with the accumulation of quorum-sensing molecules in the cell supernatant of this mutant strain. Therefore, our data revealed that overexpression of the efflux pump EmrCAB via mutation and/or derepression of EmrR confers quinolone resistance and alters quorum-sensing signaling in C. violaceum, and that point mutation in emrR can contribute to emergence of antibiotic resistance in bacteria.


A workshop for receptionists in mental health settings.
This article addresses an area which has received little attention in the mental health field--the education and training needs of receptionists. Factors that can assist or impede the contribution of this important position are identified. The authors describe the process used to design and deliver a one-day workshop to enhance receptionists' interpersonal skills, and to increase their understanding of mental health issues. The benefits of this experience for the individual and for mental health organizations are described.


Circulating Dickkopf-1 and osteoprotegerin in patients with early and longstanding rheumatoid arthritis.
Rheumatoid arthritis (RA) is characterized by inflammation of the synovial membrane, leading to invasion of synovial tissue into the adjacent cartilage matrix with degradation of articular cartilage and bone as a consequence. Dickkopf-1 (DKK-1) and osteoprotegerin (OPG) have been demonstrated to be key molecules involved in bone erosion and bone remodeling. The aim of this study was to explore the potential role of DKK-1 and OPG in different stage of RA. The protein levels of DKK-1 and OPG were detected by ELISA. The serum samples were collected from 300 patients with RA and 60 healthy controls. Of which, 150 RA patients were defined as early RA (disease duration < or = 1 year), and other 150 RA patients were defined as longlasting RA (disease duration > or = 5 years). At the time of serum sampling, various clinical and laboratory parameters were assessed. The correlations of DKK-1 or OPG and clinical/laboratory parameters were analyzed. The serum level of DKK-1 was elevated in patients with longstanding RA compared with healthy controls, while no significant difference was observed between the two groups in the level of OPG. In contrast, in early RA patients, the circulating OPG was elevated, while there was no significant difference between the two groups in expression of DKK-1. The serum DKK-1 was correlated with Sharp score and DAS28 in longstanding RA patients. In early RA, age was the only parameter that was significantly related to serum OPG. There was a cross-talk between DKK-1 and OPG, which involved in bone destruction in RA. In different stage of RA, DKK-1 and OPG may play different roles in the pathogenesis of RA.


Construct validity of the Social Physique Anxiety Scale in a French adolescent sample.
We conducted a series of studies to investigate the psychometric properties of the Social Physique Anxiety Scale (SPAS; Hart, Leary, & Rejeski, 1989) among a total sample of 1,563 nonclinical French adolescents. The, first study provided support for the item content of the preliminary version of the French SPAS for adolescents. Then, the second study supported the convergent validity of the English and French version of the SPAS. Finally, Studies 3 to 6 provided support for the factor validity, measurement invariance (across genders, age groups and samples), latent mean structure invariance (across age category and samples), reliability, convergent validity, and criterion-related validity of a 7-item version of the SPAS.


Serum vitamin A distribution curve for children aged 2-6 y known to have adequate vitamin A status: a reference population.
Serum vitamin A was determined before and 30-45 d after the administration of 60.6 mg (212 mumol) vitamin A to 544 Brazilian children residing in slum areas of Recife. The frequency-distribution curves were compared in a subgroup of children whose vitamin A status was assessed initially by the relative-dose-response (RDR) test. The curves of children with negative (adequate status) and positive (inadequate status) RDR tests were different. The difference disappeared after supplementation. The shape of the distribution curve after supplementation was close to normal with a mean, median, and 95% confidence interval of 1.78 +/- 0.49, 1.68, and 1.02-2.90 mumol/L, respectively. The postsupplementation curve derived from this underprivileged child population may serve as a reference for diagnostic, surveillance, and program-evaluation purposes.


Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan.
Early biomarkers of tumour response are needed to discriminate between responders and non-responders to radiotherapy. We evaluated the ability of ceramide, a bioactive sphingolipid, to predict tumour sensitivity in patients treated by hypofractionated stereotactic body radiation therapy (SBRT) combined with irinotecan chemotherapy. Plasma levels of total ceramide and of its subspecies were measured before and during treatment in 35 patients with liver and lung oligometastases of colorectal cancer included in a phase II trial. Cer levels were quantified by LC-ESI-MS/MS and compared to tumour volume response evaluated one year later by CT-scan. Pretreatment plasma ceramide levels were not indicative of tumour response. Nevertheless, the levels of total ceramide and of its 4 main subspecies were significantly higher at days 3 and 10 of treatment in objective responders than in non-responders. According to Kaplan-Meier curves, almost complete tumour control was achieved at 1year in patients with increased total ceramide levels whereas 50% of patients with decreased levels experienced an increase in tumour volume. Total plasma ceramide is a promising biomarker of tumour response to SBRT combined with irinotecan that should enable to segregate patients with high risk of tumour escape.


Desulfurization of light gas oil in immobilized-cell systems of Gordona sp. CYKS1 and Nocardia sp. CYKS2.
Desulfurizations of a model oil (hexadecane containing dibenzothiophene (DBT)) and a diesel oil by immobilized DBT-desulfurizing bacterial strains, Gordona sp. CYKS1 and Nocardia sp. CYKS2, were carried out. Celite bead was used as a biosupport for cell immobilization. Seven-eight cycles of repeated-batch desulfurization were conducted for each strain. Each batch reaction was carried out for 24 h. In the case of model oil treatment with strain CYKS1, about 4.0 mM of DBT in hexadecane (0.13 g sulfur l(oil)(-1)) was desulfurized during the first batch, while 0.25 g sulfur l(oil)(-1) during the final eighth batch. The mean desulfurization rate increased from 0.24 for the first batch to 0.48 mg sulfur l(dispersion)(-1) h(-1) for the final batch. The sulfur content in the light gas oil was decreased from 3 to 2.1 g l(oil)(-1) by strain CYKS1 in the first batch. The mean desulfurization rate was 1.81 mg sulfur l(dispersion)(-1) h(-1), which decreased slightly when the batch reaction was repeated. No significant changes in desulfurization rate were observed with strain CYKS2 when the batch reaction was repeated. When the immobilized cells were stored at 4 degrees C in 0.1 M phosphate buffer (pH 7.0) for 10 days, the residual desulfurization activity was about 50 approximately 70% of the initial value.


Mobilization of respiratory metabolism in potato tubers by carbon dioxide.
Applying high concentrations of CO(2) to whole potato tubers stimulated a rapid and pronounced respiratory gas exchange, which persisted for a prolonged time. The upsurge in respiration was proportional to the applied CO(2) concentrations and was further augmented by high O(2) levels. Tests using whole potatoes, or potato tissue slices from tubers previously treated with CO(2), indicated that the rapid CO(2)-induced respiration is sensitive to cyanide during the first 24 hours of CO(2) application. The respiratory rise cannot be attributed to the emergence of a cyanide-resistant alternative electron transport pathway, although prolonged applications of CO(2), up to 72 hours, led to a gradual development of the pathway. CO(2)-stimulated respiration was accompanied by a pronounced decline in the content of starch and glucose 6-phosphate, suggesting an active utilization of respiratory substrates. The ATP content in the CO(2)-treated potatoes increased markedly, resembling similar increases in tissues undergoing respiratory upsurge.


Phosphoprotein Phosphatase 1 but Not 2A Activity Modulates Coupled-Clock Mechanisms to Impact on Intrinsic Automaticity of Sinoatrial Nodal Pacemaker Cells.
Spontaneous AP (action potential) firing of sinoatrial nodal cells (SANC) is critically dependent on protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent protein phosphorylation, which are required for the generation of spontaneous, diastolic local Ca2+ releases (LCRs). Although phosphoprotein phosphatases (PP) regulate protein phosphorylation, the expression level of PPs and phosphatase inhibitors in SANC and the impact of phosphatase inhibition on the spontaneous LCRs and other players of the oscillatory coupled-clock system is unknown. Here, we show that rabbit SANC express both PP1, PP2A, and endogenous PP inhibitors I-1 (PPI-1), dopamine and cyclic adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (DARPP-32), kinase C-enhanced PP1 inhibitor (KEPI). Application of Calyculin A, (CyA), a PPs inhibitor, to intact, freshly isolated single SANC: (1) significantly increased phospholamban (PLB) phosphorylation (by 2-3-fold) at both CaMKII-dependent Thr17 and PKA-dependent Ser16 sites, in a time and concentration dependent manner; (2) increased ryanodine receptor (RyR) phosphorylation at the Ser2809 site; (3) substantially increased sarcoplasmic reticulum (SR) Ca2+ load; (4) augmented L-type Ca2+ current amplitude; (5) augmented LCR's characteristics and decreased LCR period in intact and permeabilized SANC, and (6) increased the spontaneous basal AP firing rate. In contrast, the selective PP2A inhibitor okadaic acid (100 nmol/L) had no significant effect on spontaneous AP firing, LCR parameters, or PLB phosphorylation. Application of purified PP1 to permeabilized SANC suppressed LCR, whereas purified PP2A had no effect on LCR characteristics. Our numerical model simulations demonstrated that PP inhibition increases AP firing rate via a coupled-clock mechanism, including respective increases in the SR Ca2+ pumping rate, L-type Ca2+ current, and Na+/Ca2+-exchanger current. Thus, PP1 and its endogenous inhibitors modulate the basal spontaneous firing rate of cardiac pacemaker cells by suppressing SR Ca2+ cycling protein phosphorylation, the SR Ca2+ load and LCRs, and L-type Ca2+ current.


Heparin and PGE2 inhibit DNA synthesis in human airway smooth muscle cells in culture.
An increase in the bulk of the airway smooth muscle is a characteristic of asthma. Much of the research investigating the mechanisms of this increase in muscle has focused on mediators that are mitogenic for smooth muscle, while relatively few studies have focused on mediators inhibiting mitogenesis. In this study we have examined the effects of two mediators proposed as regulators of smooth muscle proliferation, namely heparin and prostaglandin (PG) E2, on human airway smooth muscle cells in culture stimulated with 1, 2.5, 5, and 10% fetal bovine serum (FBS) and platelet-derived growth factor AB (PDGF), 50 ng/ml. PGE2 had a biphasic effect on DNA synthesis in the presence of 1% FBS, with 10(-6) M causing inhibition and 10(-7) M causing an increase in DNA synthesis. PGE2 caused inhibition of DNA synthesis in the presence of 2.5, 5, and 10% FBS. Heparin (10 and 100 U/ml) caused an inhibition of DNA synthesis induced by 1% FBS, while 100 U/ml inhibited DNA synthesis induced by 5 and 10% FBS. PGE2 (10(-8), 10(-7), and 10(-6) M) inhibited the DNA synthesis induced by PDGF, while heparin (1, 10, and 100 U/ml) had no effect. These results indicate that both PGE2 and heparin may have a role in the control of human airway smooth muscle cell growth.


Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer.
The tumor suppressor gene (TSG) p53 and the proto-oncogene bcl-2 have been shown to be involved in the regulation of cell growth and apoptosis and have been implicated in hormone refractory prostate cancer (PC) and poor prognosis. The goal of this study was to determine the clinical utility of the presence of p53 and bcl-2 immunohistochemical (IHC) protein in the primary tumor as predictors of disease progression following radical prostatectomy (RP). The expression of p53 and bcl-2 was evaluated in archival paraffin-embedded RP specimens from 175 patients followed from 1 to 9 years (mean = 4.6 years) and correlated with stage, grade, race and serologic (PSA) recurrence following surgery. Overexpression of bcl-2 was noted in 47 of 175 (26.9%) patients; these patients had a significantly higher 5-year failure rate than those who did not overexpress bcl-2 (67.0% versus 30.7%). Expression of p53 was noted in 114 of 175 (65.1%) patients with a 5-year failure rate of 51.1% compared with a 5-year failure rate of only 22% in p53 negative patients. When expression rates for p53 and bcl-2 were combined, the 5-year failure rate was 75.3%. Conversely, when both p53 and bcl-2 IHC staining were negative, the 5-year failure rate was 20.4%. Univariate Kaplan-Meier analysis showed a statistically significant difference between p53 and bcl-2 positive and negative patients (p < 0.001). Multivariate Cox Regression Analysis with backward elimination controlling for age, race, stage and grade showed both p53 (p = .0185) and bcl-2 (p = .004) to be independent predictors of disease-free survival. p53 and bcl-2 appear to be important biomarkers that predict recurrence in clinically localized PC after RP.


Bisphosphonates in the treatment of skeletal metastases.
Metastatic bone disease puts an enormous burden on patients and health care resources. Disruption of normal bone homeostasis by bone metastases leads to troublesome skeletal complications, such as bone pain, pathologic fractures, hypercalcemia of malignancy, and spinal cord compression. Bisphosphonates are an effective treatment for skeletal complications. These agents act primarily by initiating biochemical processes that ultimately result in apoptosis of osteoclasts, but they also have a number of other antitumor functions (eg, inhibition of angiogenesis). At present, the most widely used bisphosphonates are oral clodronate and intravenous pamidronate and zoledronic acid. Although these agents are effective in reducing skeletal complications, they are associated with varying safety and convenience issues. More recently, the availability of ibandronate as intravenous and oral formulations represents a new alternative for the treatment of metastatic bone disease. Further studies are necessary to establish the comparative benefits of bisphosphonates in metastatic bone disease.


Randomized, open label, multicenter trial of cefixime compared with amoxicillin for treatment of acute otitis media with effusion.
Cefixime, a new third generation cephalosporin antibiotic for oral use, was evaluated for safety and efficacy in the treatment of children with acute otitis media with effusion. Fifteen United States clinical investigators participated in the multicenter clinical trial. One hundred twenty children were randomly assigned to a 10-day course of either cefixime, 8 mg/kg, given daily (qd) (60 patients) or amoxicillin, 40 mg/kg/day, administered in three divided doses (60 patients). Tympanocentesis was performed on each patient before therapy was initiated. Pathogens were isolated from a middle ear aspirate in 88% of the cases. Of the specimens from which pathogens were cultured, 33% yielded Haemophilus sp., 41% Streptococcus pneumoniae and 6% Branhamella catarrhalis. Of the 120 patients, 64 (30 cefixime and 34 amoxicillin) were evaluable for assessment of efficacy. Favorable clinical responses (cure or improvement) were obtained in 93% of cefixime-treated patients and in 94% of amoxicillin-treated patients. Overall, bacteriologic eradication rates (as determined by clinical criteria) were 94 and 95%, respectively. Clinical failure or relapse was documented in 2 of 30 (7%) patients treated with cefixime and in 2 of 34 (6%) patients treated with amoxicillin. Gastrointestinal disturbance and rash were significantly more common in children treated with cefixime (22 and 15%, respectively) than in those taking amoxicillin (8 and 2%, respectively), but in only one case was it necessary to discontinue medication because of these adverse effects (rash). Results of this study demonstrate that cefixime given once daily is as safe and effective as amoxicillin in the treatment of acute otitis media with effusion in children and has the possible advantage of less frequent dosing.


Evidence for laser-induced formation of solvated electrons in room temperature ionic liquids.
The photolytic generation of solvated electrons was observed for the first time in two room temperature ionic liquids (RTILs), trihexyltetradecylphosphonium bis(trifluoromethylsulfonyl)imide (IL) and 1-butyl-1-methyl-pyrrolidinium bis(trifluoromethylsulfonyl)imide (IL). A 70 fs UV-pulse was used to excite the RTILs, while the transient response was monitored in the visible and near-infrared spectral regions. Immediately after excitation, a pulse duration limited rise of the induced absorption indicated the formation of solvated electrons suggesting the existence of pre-formed traps in RTILs. A broad transient absorption spectrum with a full width at half maximum of about 0.9 eV, typical for solvated electrons, was reconstructed from the transient profiles. Wavelength-independent relaxation dynamics at longer delay times suggest a lifetime of solvated electrons in the ns regime in agreement with results from pulse radiolysis studies. Adding 1,1-dimethylpyrrolidinium iodide to IL led to an increase of the UV absorbance and consequently, to an increase of the yield of solvated electrons. Furthermore, this solute is an efficient electron scavenger causing the transients to decay within about 40 ps.


Coordinate regulation of membrane cAMP by Ca2+-inhibited adenylyl cyclase and phosphodiesterase activities.
Activation of store-operated Ca(2+) entry inhibits type 6 adenylyl cyclase (EC; AC(6); Yoshimura M and Cooper DM. Proc Natl Acad Sci USA 89: 6712-6720, 1992) activity in pulmonary artery endothelial cells. However, in lung microvascular endothelial cells (PMVEC), which express AC(6) and turn over cAMP at a rapid rate, inhibition of global (whole cell) cAMP is not resolved after direct activation of store-operated Ca(2+) entry using thapsigargin. Present studies sought to determine whether the high constitutive phosphodiesterase activity in PMVECs rapidly hydrolyzes cAMP so that Ca(2+) inhibition of AC(6) is difficult to resolve. Direct stimulation of adenylyl cyclase using forskolin and inhibition of type 4 phosphodiesterases using rolipram increased cAMP and revealed Ca(2+) inhibition of AC(6). Enzyme activity was assessed using PMVEC membranes, where Ca(2+) and cAMP concentrations were independently controlled. Endogenous AC(6) activity exhibited high- and low-affinity Ca(2+) inhibition, similar to that observed in C6-2B cells, which predominantly express AC(6). Ca(2+) inhibition of AC(6) in PMVEC membranes was observed after enzyme activation and inhibition of phosphodiesterase activity and was independent of the free cAMP concentration. Thus, under basal conditions, the constitutive type 4 phosphodiesterase activity rapidly hydrolyzes cAMP so that Ca(2+) inhibition of AC(6) is difficult to resolve, indicating that high phosphodiesterase activity works coordinately with AC(6) to regulate membrane-delimited cAMP concentrations, which is important for control of cell-cell apposition.


Association between the ACTN3 R577X polymorphism and artistic gymnastic performance in Italy.
The ACTN3 (R577X) gene encodes for a structural protein that is exclusively expressed in the Z-disc of type II muscle fibers. Homozygosis (577XX) for the stop codon in the ACTN3 polymorphism results in alpha-actinin-3 complete deficiency. Previous studies have shown low frequencies of the ACTN3 XX genotype in elite sprinters compared to the general population. This study tests 35 Italian elite gymnasts and 53 controls. ACTN3 XX genotype (2.8% vs. 18.8%; p < 0.04) and X allele (27.1% vs. 43.3%; p < 0.04) frequencies were significantly lower in gymnasts compared to controls. The ACTN3 XX genotype was underrepresented in female and male gymnasts compared to controls, but was only significant for males (male: 0% vs. 16.1%, p < 0.04; female: 5.5% vs. 22.7%, p = 0.39). These results suggest that alpha-actinin-3 is beneficial to skeletal muscle function in generating forceful contractions at high velocity. In conclusion, our results associated the ACTN3 R577X polymorphism with male and possibly female elite gymnastic performance.


Direct enzyme-linked aptamer assay (DELAA) for diagnosis of toxoplasmosis by detection of SAG1 protein in mice and humans.
Toxoplasma gondii is a single-celled parasite commonly found in mammals and birds. Diagnosis of toxoplasmosis largely depends on measurements of the antibody and/or antigen and Toxoplasma DNAs due to the presence of tissue dwelling duplicating tachyzoites, or quiescent cysts in latent infection of the parasite. As a major surface antigen of T.gondii tachyzoites, SAG1 is a key molecule for laboratory diagnosis. However, there are no methods available yet for SAG1 detection using aptamer-based technology. Recombinant SAG1 (r-SAG1) of Toxoplasma WH3 strain (type Chinese 1) was expressed in E.coli and subjected to the synthetic oligonucleotide library for selection of nucleic acid aptamers which target the r-SAG1 antigen, with systematic evolution of ligands by exponential enrichment (SELEX) strategy. The specific aptamers were screened out and used in direct enzyme-linked aptamer assay (DELAA) for detection of native SAG1 (n-SAG1) obtained from tachyzoite lysates, mouse sera of acute infection, and human sera that had been verified for Toxoplasma DNAs by PCR amplification. As results, the soluble r-SAG1 protein was obtained from E.coli lysates by purification and identification with immunoblotting, followed by biotinylation. The selected aptamers were amplified by PCR and DNA sequencing. The results showed that the aptamer-2, with the highest affinity to n-SAG1 in the sera of animals with minimal difference in the four aptamer candidates, has a high specificity and sensitivity when used in detection of n-SAG1 in the sera of humans when compared with the commercial kit of ELISA for T.gondii circulating antigen test. We concluded that a new direct enzyme-linked aptamer assay (DELAA) was developed for the detection of the n-SAG1 protein of T. gondii. With increased sensitivity and specificity, stability, easy and cheap preparation, the aptamer-based technology is considered an efficient method for the diagnosis of active as well as reactivated toxoplasmosis.


Radio frequency electromagnetic exposure: tutorial review on experimental dosimetry.
Radio frequency (RF) dosimetry is the quantification of the magnitude and distribution of absorbed electromagnetic energy within biological objects that are exposed to RF fields. At RF, the dosimetric quantity, which is called the specific absorption rate (SAR), is defined as the rate at which energy is absorbed per unit mass. The SAR is determined not only by the incident electromagnetic waves but also by the electrical and geometric characteristics of the irradiated subject and nearby objects. It is related to the internal electric field strength (E) as well as to the electric conductivity and the density of tissues; therefore, it is a suitable dosimetric parameter, even when a mechanism is determined to be "athermal." SAR distributions are usually determined from measurements in human models, in animal tissues, or from calculations. This tutorial describes experimental techniques that are used commonly to determine SAR distributions along with the SAR limitations and unresolved problems. The methods discussed to obtain point, planar, or whole-body averaged SARs include the use of small E-field probes or measurement of initial rate of temperature rise in an irradiated object.


[Study on infrared spectrum change of Ganoderma lucidum and its extracts].
From the determination of the infrared spectra of four substances (original ganoderma lucidum and ganoderma lucidum water extract, 95% ethanol extract and petroleum ether extract), it was found that the infrared spectrum can carry systematic chemical information and basically reflects the distribution of each component of the analyte. Ganoderma lucidum and its extracts can be distinguished according to the absorption peak area ratio of 3 416-3 279, 1 541 and 723 cm(-1) to 2 935-2 852 cm(-1). A method of calculating the information entropy of the sample set with Euclidean distance was proposed, the relationship between the information entropy and the amount of chemical information carried by the sample set was discussed, and the authors come to a conclusion that sample set of original ganoderma lucidum carry the most abundant chemical information. The infrared spectrum set of original ganoderma lucidum has better clustering effect on ganoderma atrum, Cyan ganoderma, ganoderma multiplicatum and ganoderma lucidum when making hierarchical cluster analysis of 4 sample set. The results show that infrared spectrum carries the chemical information of the material structure and closely relates to the chemical composition of the system. The higher the value of information entropy, the much richer the chemical information and the more the benefit for pattern recognition. This study has a guidance function to the construction of the sample set in pattern recognition.


RNA editing in maize chloroplasts is a processing step independent of splicing and cleavage to monocistronic mRNAs.
The psbB operon contained in the plastomes of higher plants consists of the genes psbB, psbH, petB and petD. The primary transcript of this operon is subject to a series of processing steps which include cleavages resulting in four monocistronic mRNAs and splicing of the petB and petD transcripts. A search for editing sites within the two latter transcripts from maize led us to the detection of one editing site within the petB coding region which is conserved at the DNA level in other graminean species and in tobacco. This shows that editing must be considered as an additional processing step of the psbB operon encoded primary transcript. As is evident from cDNA sequences derived from the dicistronic and/or unspliced petB/D transcripts which are completely edited, editing is an early step of mRNA processing which precedes both splicing and cleavage to the monocistronic mRNAs and which must, therefore, be independent of the latter two steps. This conclusion is confirmed by a similar observation with the editing site of the rpl2 transcript which is contained in the polycistronic transcript of the rpoA operon, although here only partial editing is observed for the unspliced dicistronic rpl23/rpl2 transcript.


Gingipains in the culture supernatant of Porphyromonas gingivalis cleave CD4 and CD8 on human T cells.
Porphyromonas gingivalis has been shown to attack host defense systems through proteolytic cleavage of a wide variety of members of the systems. In this study, we examined the ability of P. gingivalis culture supernatant to alter the expression of human T cell surface proteins. As judged by flow cytometric analysis, detection of CD4 expression was completely eliminated by the supernatant, but CD8 was less sensitive. When the culture supernatant was added with reducing agents, proteolytic activity was enhanced, resulting in the cleavage of CD8. Mitogenic response of T cells to phytohemagglutinin or concanavalin A was decreased by the treatment of the cells with the culture supernatant of P. gingivalis. The three forms of gingipains (high molecular mass arginine-specific gingipain, arginine-specific gingipain 2 and lysine-specific gingipain) purified from the culture supernatant of P. gingivalis actively cleaved CD4 and CD8 on human T cells, indicating that proteolytic activity of the culture supernatant was due to gingipains. These results suggest that cysteine proteinases like gingipains released from P. gingivalis cleave T cell surface proteins and impede T cell function.


Hepatitis C Virus (HCV) Vertical Transmission in 12-Month-Old Infants Born to HCV-Infected Women and Assessment of Maternal Risk Factors.
Background. Hepatitis C virus (HCV) is an underappreciated cause of pediatric liver disease, most frequently acquired by vertical transmission (VT). Current guidelines that include the option of screening infants for HCV RNA at 1-2 months are based on data prior to current real-time polymerase chain reaction (PCR)-based testing. Previous studies have demonstrated VT rates of 4%-15% and an association with high maternal viral load. We evaluated HCV RNA in infants with HCV VT and assessed maternal risk factors in a prospective cohort in Cairo, Egypt. Methods. Pregnant women were screened for HCV from December 2012 to March 2014. For those with HCV viremia, their infants were tested at 12 months for HCV RNA using real-time PCR. Maternal risk factors assessed for HCV VT association included HCV RNA levels, mode of delivery, and maternal IL28B genotype. Results. Of 2514 women screened, a total of 54 women were viremic (2.1%) and delivered 56 infants. Of those, 51 infants of 49 women were tested at 12 months of age. Only 7 infants were viremic, with an HCV VT rate of 14.3% (7 of 49). Median HCV RNA in the infants was 2100 IU/mL. None of the maternal risk factors analyzed were associated with transmission. Conclusions. In Egypt where HCV is highly endemic, we observed an overall 12-month HCV VT rate of 14.3%. Further studies should focus on better identification of pregnant women more likely to vertically transmit HCV and earlier testing of infants to identify those likely to develop chronicity.


The effective management of atopic dermatitis in school-age children.
The terms atopic eczema and atopic dermatitis (AD) are synonymous. In this article, the latter term is used. AD can affect all age groups but is most commonly associated with children. It is a dry-skin condition, the severity of which can vary from person to person. It is not contagious. In mild forms of the condition the skin is dry, hot and itchy, while in more severe cases the skin can be broken, raw and bleeding, or produce vesicles and papules that may become eroded.


Superoxide does not inhibit glyceryl trinitrate-rabbit aortic strip-mediated relaxation of rabbit Taenia coli. Evidence against a role for nitric oxide itself as the smooth muscle active drug metabolite?
This study was designed to test the hypothesis that nitric oxide (NO) is the relaxant metabolite produced by metabolic activation of glyceryl trinitrate (GTN) in rabbit aortic strip (RAS). Superoxide anion, an inactivator of NO, was included in a two-tissue bioassay in which rabbit Taenia coli strip (RTCS) relaxed to GTN in the presence of RAS. Superoxide as generated by xanthine (10 microM)/ xanthine oxidase (20 mU/ml) failed to attenuate relaxations of RTCS to GTN (0.1 nM-10 microM) and RAS, compared with the untreated control. In contrast, superoxide attenuated the relaxation of RTCS to both authentic NO gas and to SIN-1 (0.1 nM-10 microM), a known spontaneous releaser of NO; the attenuation of RTCS relaxation to NO gas was reversed by superoxide dismutase (100 units/ml). In addition, another drug that has been reported to scavenge NO, hydroquinone, did not attenuate the RTCS relaxation to GTN. These results suggest that biotransformation of GTN in vascular smooth muscle that leads to relaxation is caused by a NO-containing species (i.e. a S-nitrosothiol). Such a molecule would be less susceptible to inactivation by superoxide anion and hydroquinone.


Time-resolved tryptophan fluorescence anisotropy investigation of bacteriophage M13 coat protein in micelles and mixed bilayers.
Coat protein of bacteriophage M13 is examined in micelles and vesicles by time-resolved tryptophan fluorescence and anisotropy decay measurements and circular dichroism experiments. Circular dichroism indicates that the coat protein has alpha-helix (60%) and beta-structure (28%) in 700 mM sodium dodecyl sulfate micelles and predominantly beta-structure (94%) in mixed dimyristoylphosphatidylcholine/dimyristoylphosphatidic acid (80/20 w/w) small unilamellar vesicles. The fluorescence decay at 344 nm of the single tryptophan in the coat protein after excitation at 295 or 300 nm is a triple exponential. In the micelles the anisotropy decay is a double exponential. A short, temperature-independent correlation time of 0.5 +/- 0.2 ns reflects a rapid depolarization process within the coat protein. The overall rotation of the coat protein-detergent complex is observed in the decay as a longer correlation time of 9.8 +/- 0.5 ns (at 20 degrees C) and has a temperature dependence that satisfies the Stokes-Einstein relation. In vesicles at all lipid to protein molar ratios in the range from 20 to 410, the calculated order parameter is constant with a value of 0.7 +/- 0.1 from 10 to 40 degrees C, although the lipids undergo the gel to liquid-crystalline phase transition. The longer correlation time decreases gradually on increasing temperature. This effect probably arises from an increasing segmental mobility within the coat protein. The results are consistent with a model in which the coat protein has a beta-structure and the tryptophan indole rings do not experience the motion of the lipids in the bilayer because of protein-protein aggregation.


Turn-Number-Dependent Motion Behavior of Catalytic Helical Carbon Micro/Nanomotors.
Helical micro/nanomotors (MNMs) can be propelled by external fields to swim through highly viscous fluids like complex biological environments, which promises miniaturized robotic tools to perform assigned tasks at small scales. However, the catalytic propulsion method, most widely adopted to drive MNMs, is seldom studied to actuate helical MNMs. Herein, we report catalytic helical carbon MNMs (CHCM) by sputtering Pt onto helical carbon nano-coils (HCNC) that are in bulk prepared by a thermal chemical vapor deposition method. The Pt-triggered H2 O2 decomposition can drive the MNMs by an electrokinetic mechanism. The MNMs demonstrate versatile motion behaviors including both directional propulsion and rotation depending on the turn number of the carbon helix. Besides, due to the ease of surface functionalization on carbon and other properties such as biocompatibility and photothermal effect, the helical carbon MNMs promise multifunctional applications for biomedical or environmental applications.


[Advances in the effects of pH value of micro-environment on wound healing].
Wound healing is a complex regeneration process, which is affected by lots of endogenous and exogenous factors. Researches have confirmed that acid environment could prevent wound infection and accelerate wound healing by inhibiting bacteria proliferation, promoting oxygen release, affecting keratinocyte proliferation and migration, etc. In this article, we review the literature to identify the potential relationship between the pH value of wound micro-environment and the progress of wound healing, and summarize the clinical application of variation of pH value of micro-environment in wound healing, thereby to provide new treatment strategy for wound healing.


Composition of hyaluronan affects wound healing in the rabbit maxillary sinus.
Hyaluronan (HA) is a ubiquitous component of the extracellular matrix. HA and its derivatives have been used in the sinuses to reduce scarring and possibly promote wound healing. However, in recent animal studies, HA esters exhibited inflammatory effects. Mitomycin C (MMC) is another potential antiscarring treatment. This study prospectively evaluated the effects of three different HA constructs on wound healing in the rabbit maxillary sinus: (i) a novel cross-linked HA hydrogel, (ii) the cross-linked HA gel containing covalently bound MMC, and (iii) a commercially available woven HA ester (Merogel). Ostia were created with a 4-mm otologic drill in the maxillary sinuses of 15 New Zealand white rabbits with one side randomly chosen for treatment. After 14 or 21 days the size of the maxillary ostia were recorded and the tissue was examined under light microscopy. Sinuses treated with the novel HA and HA-MMC hydrogels showed an increased ostial diameter compared with untreated controls. Woven HA ester-treated sinuses showed no improvement, with a trend toward a smaller ostium than controls. Histological examination showed that woven HA ester tended to cause increased fibrosis and granulomatous inflammation, and heterophilia was slightly increased in the HA hydrogel-treated sinuses. Blinded observation noted foamy macrophages surrounding the residual woven HA ester in each specimen while no similar reaction was noted near the residual HA or HA-MMC hydrogels. This study suggests that the degree of ostial narrowing, inflammation, and fibrosis depends on the formulation of the HA used. Minimal, if any, additional benefit is seen with addition of MMC to the HA hydrogel in this pilot study.


Effects of Climate and Rodent Factors on Hemorrhagic Fever with Renal Syndrome in Chongqing, China, 1997-2008.
China has the highest global incidence of hemorrhagic fever with renal syndrome (HFRS), constituting 90% of the cases in the world. Chongqing, located in the Three Gorges Reservoir Region, has been experiencing differences in the occurrence of HFRS from 1997 to 2008. The current study was designed to explore the effects of climate and rodent factors on the transmission of HFRS in Chongqing. Data on monthly HFRS cases, rodent strains, and climatic factors were collected from 1997 to 2008. Spatio-temporal analysis indicated that most HFRS cases were clustered in central Chongqing and that the incidence of HFRS decreased from 1997 to 2008. Poisson regression models showed that temperature (with lagged months of 0 and 5) and rainfall (with 2 lagged months) were key climatic factors contributing to the transmission of HFRS. A zero-inflated negative binomial model revealed that rodent density was also significantly associated with the occurrence of HFRS in the Changshou district. The monthly trend in HFRS incidence was positively associated with rodent density and rainfall and negatively associated with temperature. Possible mechanisms are proposed through which construction of the dam influenced the incidence of HFRS in Chongqing. The findings of this study may contribute to the development of early warning systems for the control and prevention of HFRS in the Three Gorges Reservoir Region.


Management of chronic middle ear effusion.
Management of chronic middle ear effusion must center around the reestablishment of normal eustachian tube function. If fluid does not clear with medical management, aspiration becomes necessary. A prosthetic eustachian tube is placed in the tympanic membrane in order to artificially ventilate the middle ear space while primary etiologic factors are being corrected. Unless recurrent or chronic ear disease of this nature is diligently treated, progressive damage may bring about irreversible hearing loss and the potentially dangerous disease, cholesteatoma of the ear.


Residential PTSD treatment for female veterans with military sexual trauma: does a history of childhood sexual abuse influence outcome?
This study examined whether a history of childhood sexual abuse (CSA) influenced treatment outcome among female veterans with an index trauma of military sexual trauma (MST) receiving residential treatment for posttraumatic stress disorder (PTSD). One hundred and ten female veterans, 61 with a history of CSA and 49 without, were compared on pre-treatment demographic and symptom measures, as well as treatment outcome, which were assessed with the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist-Stressor Specific Version (PCL-S), and Depression Inventory-Second edition (BDI-II). Veterans received cognitive processing therapy (CPT) as the primary trauma-focused treatment. Study findings showed that these two groups did not significantly differ on pre-treatment variables or treatment outcome. Results suggest that CPT delivered in a residential treatment program was effective for female veterans with PTSD related to MST, with and without a history of CSA.


Selenium-catalyzed oxidations with aqueous hydrogen peroxide. 2. Baeyer-Villiger reactions in homogeneous solution.
Several diselenides were tested for catalytic activity in Baeyer-Villiger reactions with 60% aqueous hydrogen peroxide. Bis[3,5-bis(trifluoromethyl)phenyl] diselenide forms the corresponding 3,5-bis(trifluoromethyl)benzene seleninic acid in situ, which is a highly reactive and selective catalyst for the oxidation of carbonyl compounds in 1,1,1,3,3,3-hexafluoro-2-propanol, 2,2,2-trifluoroethanol, or dichloromethane.


Parental Knowledge, Attitudes and Practices Towards Paediatric Ear Infections in Riyadh, Saudi Arabia: A quantitative study.
This study aimed to assess the knowledge, attitude and care-seeking practices of parents towards childhood ear infections in Riyadh, Saudi Arabia. This quantitative cross-sectional study was conducted in Riyadh, Saudi Arabia, between April and June 2018. An online survey was sent to a random selection of parents who were ≥18 years old with children of ≤10 years old. Associations between parental knowledge, attitude, care-seeking practices, socioeconomic status, level of education and age were assessed using the chi square test and logistic regression analysis. A total of 782 subjects participated in this study (response rate: 78.2%). Most respondents were knowledgeable (76.2%), had a positive attitude (78.9%) and had positive care-seeking practices (89.5%). There was a statistically significant difference on both bivariate and multivariate analyses (P <0.05) between parental care seeking practice and knowledge. Parents who sought modern approaches to treatment were found to be almost nine times more likely to have a good attitude towards ear infections than those who did not seek treatment (odds ratio = 8.907, 95% confidence interval = 2.655-34.928; P <0.001). A statistically significant relationship was found between good care-seeking practice and age, as well as socioeconomic status (P <0.05 each). This study showed that knowledge, attitude and practice regarding paediatric ear infections were positive in the majority of parents in Riyadh, Saudi Arabia. Future studies should assess other factors that enhance the knowledge, attitude and practices regarding ear infections.


Preventing microalbuminuria in type 2 diabetes.
The multicenter double-blind, randomized Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) was designed to assess whether angiotensin-converting-enzyme inhibitors and non-dihydropyridine calcium-channel blockers, alone or in combination, prevent microalbuminuria in subjects with hypertension, type 2 diabetes mellitus, and normal urinary albumin excretion. We studied 1204 subjects, who were randomly assigned to receive at least three years of treatment with trandolapril (at a dose of 2 mg per day) plus verapamil (sustained-release formulation, 180 mg per day), trandolapril alone (2 mg per day), verapamil alone (sustained-release formulation, 240 mg per day), or placebo. The target blood pressure was 120/80 mm Hg. The primary end point was the development of persistent microalbuminuria (overnight albumin excretion, > or =20 microg per minute at two consecutive visits). The primary outcome was reached in 5.7 percent of the subjects receiving trandolapril plus verapamil, 6.0 percent of the subjects receiving trandolapril, 11.9 percent of the subjects receiving verapamil, and 10.0 percent of control subjects receiving placebo. The estimated acceleration factor (which quantifies the effect of one treatment relative to another in accelerating or slowing disease progression) adjusted for predefined baseline characteristics was 0.39 for the comparison between verapamil plus trandolapril and placebo (P=0.01), 0.47 for the comparison between trandolapril and placebo (P=0.01), and 0.83 for the comparison between verapamil and placebo (P=0.54). Trandolapril plus verapamil and trandolapril alone delayed the onset of microalbuminuria by factors of 2.6 and 2.1, respectively. Serious adverse events were similar in all treatment groups. In subjects with type 2 diabetes and hypertension but with normoalbuminuria, the use of trandolapril plus verapamil and trandolapril alone decreased the incidence of microalbuminuria to a similar extent. The effect of verapamil alone was similar to that of placebo.


The carbohydrate maintenance properties of an experimental sports drink.
The effects of an experimental sports drink (Q) were compared with a commercial sports drink (D) of proven ergogenic efficacy. Seven highly trained subjects performed two hours of cycle ergometry exercise at approximately 65% maximal aerobic power (VO2 max) while receiving levels of Q and D in quantities designed to supply approximately 28% of the total energy requirement of the exercise task. Both Q and D formulations were supplied at 15 minute intervals at 16 degrees C, in volumes required to provide equivalent carbohydrate loads from two products of differing concentrations and compositions. Q was equally as effective as D in terms of the maintenance of plasma glucose concentrations during exercise, while selected physiological indices of work performance favoured Q. However, the time course of plasma glucose concentration changes during and after exercise indicated a trend towards more rapid uptake and assimilation of carbohydrate in the case of Q. The findings suggest that Q may provide a more readily available carbohydrate source during exercise and may enhance work performance through its ergogenic properties.


Tolerability and efficacy of colestipol hydrochloride for accelerated elimination of teriflunomide.
Teriflunomide is an oral disease modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. Teriflunomide' s pharmacokinetics (PK) contribute to its slow elimination, on average taking 6-8 months, though it can take up to 2 years in some instances. This slow elimination can become problematic in certain clinical situations - such as during pregnancy, when teriflunomide has potential teratogenic effects. In such scenarios, an accelerated elimination procedure (AEP) is recommended. Currently, AEPs with oral cholestyramine or activated charcoal are available but are restricted by adverse effects, limited administration routes, and dosing frequencies. A single-center, PK interaction study was performed in a total of 14 healthy volunteers, to investigate colestipol hydrochloride (HCl) as an alternative to cholestyramine for the elimination of teriflunomide. Participants received teriflunomide for 14 days, followed by an AEP with colestipol HCl for 15 days. The administration of colestipol HCl for 15 days was sufficient to reduce plasma teriflunomide concentrations by greater than 96%. Although colestipol HCl did not completely eliminate teriflunomide with the same effectiveness as cholestyramine, it may offer an alternative method for accelerated elimination of teriflunomide with potentially improved tolerability and more favorable dosing and administration options.


Psychological resilience correlates with EEG source-space brain network flexibility.
We aimed at identifying the potential relationship between the dynamical properties of the human functional network at rest and one of the most prominent traits of personality, namely resilience. To tackle this issue, we used resting-state EEG data recorded from 45 healthy subjects. Resilience was quantified using the 10-item Connor-Davidson Resilience Scale (CD-RISC). By using a sliding windows approach, brain networks in each EEG frequency band (delta, theta, alpha, and beta) were constructed using the EEG source-space connectivity method. Brain networks dynamics were evaluated using the network flexibility, linked with the tendency of a given node to change its modular affiliation over time. The results revealed a negative correlation between the psychological resilience and the brain network flexibility for a limited number of brain regions within the delta, alpha, and beta bands. This study provides evidence that network flexibility, a metric of dynamic functional networks, is strongly correlated with psychological resilience as assessed from personality testing. Beyond this proof-of-principle that reliable EEG-based quantities representative of personality traits can be identified, this motivates further investigation regarding the full spectrum of personality aspects and their relationship with functional networks.


Relationship between infection with hepatitis C virus and hepatocellular carcinoma in Japan.
The number of deaths due to HCC is increasing in Japan. Males in particular have seen a marked increase in the past 20 years, and HCV infection accounts for this increase. In patients treated with IFN and followed up for more than 12 months, HCV clearance was achieved in 29.8% and sustained normalization of ALT levels was achieved in 41.4% following IFN therapy. The incidence of HCC following IFN treatment is dependent on the effect of IFN on ALT levels. The incidence of HCC was low in patients with sustained normalization of ALT levels following IFN therapy, regardless of whether or not HCV had been eradicated. In the future, in addition to the development of therapies to eradicate HCV, treatments to lower ALT levels will also be important.


The big five personality traits: psychological entities or statistical constructs?
The present study employed multivariate genetic item-level analyses to examine the ontology and the genetic and environmental etiology of the Big Five personality dimensions, as measured by the NEO Five Factor Inventory (NEO-FFI) [Costa and McCrae, Revised NEO personality inventory (NEO PI-R) and NEO five-factor inventory (NEO-FFI) professional manual, 1992; Hoekstra et al., NEO personality questionnaires NEO-PI-R, NEO-FFI: manual, 1996]. Common and independent pathway model comparison was used to test whether the five personality dimensions fully mediate the genetic and environmental effects on the items, as would be expected under the realist interpretation of the Big Five. In addition, the dimensionalities of the latent genetic and environmental structures were examined. Item scores of a population-based sample of 7,900 adult twins (including 2,805 complete twin pairs; 1,528 MZ and 1,277 DZ) on the Dutch version of the NEO-FFI were analyzed. Although both the genetic and the environmental covariance components display a 5-factor structure, applications of common and independent pathway modeling showed that they do not comply with the collinearity constraints entailed in the common pathway model. Implications for the substantive interpretation of the Big Five are discussed.


Contributions of muscles, ligaments, and the ground-reaction force to tibiofemoral joint loading during normal gait.
The aim of this study was twofold: first, to determine which muscles and ligaments resist the adduction moment at the knee during normal walking; and second, to describe and explain the contributions of muscles, ligaments, and the ground reaction force to medial and lateral compartment loading. Muscle forces, ground reaction forces, and joint motions obtained from a dynamic optimization solution for normal walking were used as input to a three-dimensional model of the lower limb. A static equilibrium problem was solved at each instant of the gait cycle to determine tibiofemoral joint loading at the knee. Medial compartment loading was determined mainly by the orientation of the ground reaction force. Because this force vector passed medial to the knee, it applied an adduction moment about the joint during stance. In contrast, all of the force transmitted by the lateral compartment was due to muscle and ligament action. The muscles that contributed most to support and forward propulsion during normal walking (quadriceps and gastrocnemius) also contributed most to knee stability in the frontal plane. The knee ligaments, particularly those of the posterior lateral corner, provided stability to the knee at certain periods of the stance phase, when activity of the important stabilizing muscles was low.


Anti-inflammatory treatment of muscular injuries in sport. An update of recent studies.
Stretch-induced muscle injuries or strains, muscle contusions and delayed-onset muscle soreness (DOMS) are common muscle problems in athletes. Anti-inflammatory treatment is often used for the pain and disability associated with these injuries. The most recent studies on nonsteroidal anti-inflammatory drugs (NSAIDs) in strains and contusions suggest that the use of NSAIDs can result in a modest inhibition of the initial inflammatory response and its symptoms. However, this may be associated with some small negative effects later in the healing phase. Corticosteroids have generally been shown to adversely affect the healing of these acute injuries. Animal studies have suggested that anabolic steroids may actually aid in the healing process, but clinical studies are not yet available and the exact role of these drugs has yet to be determined. Studies on anti-inflammatory treatment of DOMS have yielded conflicting results. However, the effect of NSAIDs on DOMS appears small at best. Future research may have to focus on different aspects of these injuries as the emphasis on anti-inflammatory treatment has yielded somewhat disappointing results.


The Impact of High Dose Glucocorticoids on Bone Health and Fracture Risk in Systemic Vasculitides.
Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field.


Polycyclic N-heterocyclic compounds. part 59: rearrangement reactions of fused tricyclic 3-(2-bromoethyl)pyrimidin-4(3h)-ones with primary amines via a dimroth-type rearrangement.
Reaction of some fused tricyclic 3-(2-bromoethyl)pyrimidin-4(3H)-ones with primary alkyl amines gave abnormal fused 3-alkyl-4-alkyliminopyrimidines via a Dimroth-type rearrangement, as well as normal substituted 3-(2-alkylaminoethyl) derivatives in methanol. This abnormal rearrangement reaction depended on reaction solvent.


A novel one-dimensional coordination polymer, catena-poly[[diaquacobalt(II)]-mu-(2,2'-bipyridyl-3,3'-dicarboxylato-kappa4N,N':O,O')].
The title compound, [Co(C(12)H(6)N(2)O(4))(H(2)O)(2)](n), has been hydrothermally synthesized and structurally characterized. It consists of polymeric chains of [Co(mu-(2,2'-bipyridyl-3,3'-dicarboxylato-kappa(4)N,N':O,O'))(H(2)O)(2)] units, in which each Co(II) cation is octahedrally coordinated by two chelating pyridyl N atoms, two chelating carboxyl O atoms from different carboxylate groups of another bipyridyl ligand, and two water molecules as terminal ligands. A crystallographic twofold axis parallel to the chain axis, passes through the Co atom.