Modified Woodward's procedure confers functional improvement in Sprengel's deformity.
Modified Woodward's procedure improves shoulder movement and cosmesis. There is a paucity of literature reporting objective assessment of functional outcomes. We report cosmetic and functional outcomes in Sprengel's deformity treated with modified Woodward's procedure. Children aged 12 years and under, who underwent Modified Woodward's procedure from January 2006 to December 2014 were included in the prospective study. Improvement in Cavendish grade, Rigault scale, and shoulder movements was noted. Pediatric outcomes data collection instrument (PODCI) and simple shoulder test (SST) scores were assigned at the final follow-up. Statistical analysis was conducted with paired T-test and Wilcoxon signed-rank tests. Fourteen patients (one bilateral) with a mean follow-up of 4.5 years (1-8 years) were analyzed. The mean age at surgery was 5.7 years (3-12 years). Ten (71%) patients had omovertebral bars. Six patients had Klippel-Feil syndrome including one with cervical hemivertebrae with anterior chest wall deficiency. Cavendish grade and Rigault scale improved significantly (P < 0.05). Mean shoulder abduction and forward flexion improved by 37.3° (P < 0.001) and 38.7° (P < 0.001), respectively. The mean normative PODCI score was 24.07 (reported normative score ranges from -146 to 53) and the SST score was 9.64 (reported score ranges from 0 to 12). SST scores demonstrated a moderate correlation with shoulder function. Patients without associated anomalies had better cosmetic (P = 0.057) and functional (P = 0.029) improvement. Modified Woodward's procedure improved cosmesis and provided near-normal functional outcomes in children irrespective of age and sex. Better improvement was noted in children without anomalies.


Attributes of microbial associations of meat growing as xenic batch cultures in a meat juice at 4 degrees C.
Strains of Gram-positive (Carnobacterium piscicola, Leuconostoc mesenteroides subsp. mesenteroides, Brochothrix thermosphacta) and Gram-negative (Pseudomonas fragi and Hafnia alvei) bacteria isolated from minced lamb packaged under a modified atmosphere were cultivated in a meat (lamb) juice at 4 degrees C. Carbohydrates were catabolised in the order glucose > glucose 6-phosphate during the development of the population. Under an atmosphere enriched with carbon dioxide the Gram-negative portion of the population was suppressed during the exponential phase but H. alvei became the dominant organism towards the end of a protracted stationary phase of growth. With the aerobic atmosphere P. fragi catabolised creatine and became the dominant species in the stationary phase. The inability of C. piscicola to catabolise glucose 6-phosphate was reflected in its population being smaller than those of the other Gram-positive organisms (C. piscicola < L. mesenteroides subsp. mesenteroides < B. thermosphacta). During the stationary phase of growth, indigenous L-lactic acid and the D-isomer produced by leuconostocs were oxidised to acetic acid by the Gram-positive flora under an atmosphere enriched with carbon dioxide. These oxidations, which occurred after depletion of glucose, were supported by the oxygen in the system. D-Lactic and acetic acid appeared to be possible parameters for the estimation of the microbiological quality of packaged meat.


Two Ways to Examine Differential Constitutive Equations: Initiated on Steady or Initiated on Unsteady (LAOS) Shear Characteristics.
The exponential Phan⁻Tien and Tanner (PTT), Giesekus, Leonov, and modified extended Pom⁻Pom (mXPP) differential constitutive models are evaluated in two ways: with regard to steady shear characteristics and with regard to large amplitude oscillatory shear characteristics of a solution of poly(ethylene oxide) in dimethyl sulfoxide. Efficiency of the models with nonlinear parameters optimized with respect to steady shear measurements is evaluated by their ability to describe large amplitude oscillatory shear (LAOS) characteristics. The reciprocal problem is also analyzed: The nonlinear parameters are optimized with respect to the LAOS measurements, and the models are confronted with the steady shear characteristics. In this case, optimization is based on the LAOS measurements and equal emphasis is placed on both real and imaginary parts of the stress amplitude. The results show that the chosen models are not adequately able to fit the LAOS characteristics if the optimization of nonlinear parameters is based on steady shear measurements. It follows that the optimization of nonlinear parameters is much more responsible if it is carried out with respect to the LAOS data. In this case, when the optimized parameters are used for a description of steady shear characteristics, efficiency of the individual models as documented differs.


Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling.
Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as Haemophilus influenzae and Moraxella catarrhalis. As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with H. influenzae and M. catarrhalis promotes the increased resistance of biofilms to antibiotics and host clearance. Using H. influenzae mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione [DPD]) promoted increased M. catarrhalis biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted M. catarrhalis persistence beyond the levels seen in animals infected with M. catarrhalis alone. Notably, no such enhancement of M. catarrhalis persistence was observed in animals infected with M. catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We thus conclude that H. influenzae promotes M. catarrhalis persistence within polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. Moreover, these results strongly imply that successful vaccination against the unencapsulated H. influenzae strains that cause airway infections may also significantly impact chronic M. catarrhalis disease by removing a reservoir of the AI-2 signal that promotes M. catarrhalis persistence within biofilm.


Ultrasound-targeted microbubble destruction enhances delayed BMC delivery and attenuates post-infarction cardiac remodelling by inducing engraftment signals.
Delayed administration of bone marrow cells (BMCs) at 2-4 weeks after successful reperfusion in patients with acute myocardial infarction (MI) does not improve cardiac function. The reduction in engraftment signals observed following this time interval might impair the effects of delayed BMC treatment. In the present study, we aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) treatment could increase engraftment signals, enhance the delivery of delayed BMCs and subsequently attenuate post-infarction cardiac remodelling. A myocardial ischaemia/reperfusion (I/R) model was induced in Wistar rats via left coronary ligation for 45 min followed by reperfusion. Western blotting revealed that engraftment signals peaked at 7 days post-I/R and were dramatically lower at 14 days post-I/R. The lower engraftment signals at 14 days post-I/R could be triggered by UTMD treatment at a mechanical index of 1.0-1.9. The troponin I levels in the 1.9 mechanical index group were higher than in the other groups. Simultaneous haematoxylin and eosin staining and fluorescence revealed that the number of engrafted BMCs in the ischaemic zone was greater in the group treated with both UTMD and delayed BMC transplantation than in the control groups (P<0.05). Both UTMD and delayed BMC transplantation improved cardiac function and decreased cardiac fibrosis at 4 weeks after treatment, as compared with control groups (both P<0.05). Histopathology demonstrated that UTMD combined with delayed BMC transplantation increased capillary density, myocardial cell proliferation and c-kit+ cell proliferation. These findings indicated that UTMD treatment could induce engraftment signals and enhance homing of delayed BMCs to ischaemic myocardium, attenuating post-infarction cardiac remodelling by promoting neovascularization, cardiomyogenesis and expansion of cardiac c-kit+ cells.


Enhanced central and conduit pulmonary arterial reservoir function offsets reduced ductal systolic outflow during constriction of the fetal ductus arteriosus.
Constriction of the fetal ductus arteriosus (DA) has disparate effects on mean and phasic hemodynamics, as mean DA blood flow is preserved until constriction is severe, but DA systolic and diastolic blood velocities change with only mild constriction. To determine the basis of this disparity and its physiological significance, seven anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), DA, and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and during mild, moderate, and severe DA constriction (defined as pulmonary-aortic mean pressure differences of 4, 8, and 14 mmHg, respectively), produced with an adjustable snare. With DA constriction, mean DA flow was initially maintained but decreased with severe constriction (P < 0.05) in conjunction with a reduction (P < 0.05) in PT flow (i.e., right ventricular output). By contrast, DA systolic flow fell progressively during DA constriction (P < 0.001), due to decreased transmission of both early and midsystolic proximal flow-enhancing forward-running compression waves into the DA. However, DA constriction was also accompanied by greater systolic storage of blood in the PT and main PA (P < 0.025), and increased retrograde diastolic flow from compliant major branch PA (P < 0.001). Transductal discharge of these central and conduit PA blood reservoirs in diastole offset systolic DA flow reductions. These data suggest that, during DA constriction in the fetus, enhanced central and conduit PA reservoir function constitutes an important compensatory mechanism that contributes to preservation of mean DA flow via a systolic-to-diastolic redistribution of phasic DA flow.


Analytical methods for the detection of undeclared synthetic drugs in traditional herbal medicines as adulterants.
Traditional herbal medicines (THMs) are gaining popularity worldwide as an alternative approach to prescription drugs for many reasons including a general perception that they are safe. But recently there have been number of reported studies that reveal adulteration of THMs with undeclared synthetic drugs, which may potentially cause serious toxic adverse effects. This paper reviews the various classes of synthetic drugs that were found to be adulterated in THMs worldwide. The main focus is to highlight newer analytical tools used to detect adulteration. Due to the advancement in hyphenated techniques like liquid chromatography tandem mass spectrometry (LC-MS/MS), gas chromatography-tandem mass spectrometry (GC-MS/MS) and other conventional tools, it has become possible to detect synthetic drugs and their structural analogues as adulterants even if they are present in small quantities. This review also gives an overview of health-related risks after consuming such spurious products and challenges for future perspectives to control such type of malpractices.


Global signatures of protein and mRNA expression levels.
Cellular states are determined by differential expression of the cell's proteins. The relationship between protein and mRNA expression levels informs about the combined outcomes of translation and protein degradation which are, in addition to transcription and mRNA stability, essential contributors to gene expression regulation. This review summarizes the state of knowledge about large-scale measurements of absolute protein and mRNA expression levels, and the degree of correlation between the two parameters. We summarize the information that can be derived from comparison of protein and mRNA expression levels and discuss how corresponding sequence characteristics suggest modes of regulation.


Symmetry breaking of A3M2X9-type perovskite derivatives induced by polar quaternary ammonium cations: achieving efficient nonlinear optical properties.
Low-dimensional organic-inorganic metal halides, especially lead-free perovskites, are attracting increasing attention because of their environmentally friendly processing, flexible structures, chemical stability, and promising nonlinear optical properties. Herein, we report a new stable polar 0D lead-free hybrid bismuth chloride to enable the second-harmonic generation (SHG) active material (BTA)3Bi2Cl9 (BTA = benzyltriethylammonium, C6H5CH2N(C2H5)3+) that was obtained by the antisolvent vapor diffusion method and crystallized in the polar Cc space group. Its structure features organic cations surrounded by face-sharing [Bi2Cl9]3- dimers. (BTA)3Bi2Cl9 exhibits a wide direct bandgap (3.21 eV) and a strong phase-matchable SHG conversion efficiency (1.39 × KDP). Theoretical calculation reveals that the SHG response is owing to the synergistic effect of distorted inorganic [Bi2Cl9]3- anions and polar organic BTA+ cations. This work not only enriches the family of organic-inorganic A3M2X9 (A = monovalent cations; M = trivalent metal ions; and X = halide ions) NLO crystals but also provides the possibilities for further designing novel lead-free semiconducting piezoelectric, pyroelectric and ferroelectric materials.


Monocytes-macrophages phagocytosis as a potential marker for disease resistance in generation 1 of dwarf chickens.
Monocytes-macrophages play an indispensable role in the immune system. The current study investigated the effect of selection for monocytes-macrophages phagocytosis on disease resistance in generation 1 (G1) of dwarf chickens. Five hundred dwarf chickens of generation 0 (G0) were divided into high and low phagocytic index (PI) groups (HPIG and LPIG, respectively) based on their PI of monocytes-macrophages at 290 d of age. Then, 2 x 2 mating combinations were conducted. Sixty G0 chickens from another dwarf chicken group were used to measure the levels of monocytes-macrophages phagocytosis at different developmental stages. Among a total of 2,500 randomly selected G1 chickens, 2,100 individuals were used for a surviving and growing test under adverse feeding circumstances, and the other 400 individuals were tested for Salmonella Pullorum challenge. The results showed that progenies of HPIG hens (female symbol) were more resistant to Salmonella Pullorum. After challenge, the death rate of progeny from HPIG female symbol (28.9%) was only 58% that of progeny from LPIG female symbol (49.4%, P < 0.001). In addition, the natural infection rate of Salmonella Pullorum before 207 d for offspring from HPIG female symbol (35.0%) was significantly lower than that for offspring from LPIG female symbol (48.3%, P < 0.001). The natural mortality before 56 d in progeny of HPIG female symbol (22.6%) was significantly lower than that in progeny of LPIG female symbol (29.1%) with a P-value of 0.001. The G1 chickens of HPIG G0 female symbol weighed more than those born to LPIG G0 female symbol at 28 and 42 d of age, whereas the difference was not statistically significant at 56 d of age. The heritability of monocytes-macrophages phagocytosis was 0.40, which was moderate. The PI values were at a low level before 126 d and increased dramatically until they declined significantly after 294 d. It could be concluded that phagocytosis of monocytes-macrophages is a marker for breeding excellent progeny with strong disease resistance.


A monoclonal antibody specific to zeatin o-glycosyltransferases of phaseolus.
Zeatin O-xylosyltransferase and zeatin O-glucosyltransferase occur in immature embryos of Phaseolus vulgaris and P. lunatus, respectively. Purified preparations of the xylosyltransferase were used as antigen to elicit the formation of antibodies in mice. Hybridoma clones were produced by fusion of mouse spleen cells with myeloma cell line Fox-NY. A clone secreting monoclonal antibody (MAb), XZT-1, capable of immunoprecipitating both enzymes was obtained. The MAb detected a unique protein band from crude embryo extracts of each species with the correct molecular mass (50 kilodaltons) and relative charge (R(F) = 0.5 and 0.3) of the respective enzymes. Competition experiments with substrates indicated that the glycosyl dinucleotide binding sites of the enzymes are probably not involved in MAb-enzyme recognition. Western blotting of samples from vegetative tissues of P. vulgaris detected a low level of O-glucosyltransferase but not O-xylosyltransferase, in leaves. These findings suggest the occurrence of two genes in P. vulgaris coding for O-glycosylation enzymes with tissue-specific expression. The MAb will be used to screen expression libraries and to obtain pure enzymes for amino acid sequencing and for the production of additional MAbs.


Increased low-density lipoprotein S-homocysteinylation in chronic kidney disease.
Since low-density lipoprotein (LDL) S-homocysteinylation has been recently reported to enhance atherogenicity of lipoprotein, we have investigated the levels of homocysteine (Hcy) linked to LDL in chronic proteinuric patients in which lipid abnormalities highly contribute to the excess of morbidity and mortality. We used capillary electrophoresis to measure LDL-bound thiol Hcy, cysteine (Cys), cysteinylglycine (Cys-Gly), glutathione (GSH), and glutamylcysteine (Glu-Cys) in 30 chronic kidney disease (CKD) individuals and 60 healthy volunteers. We found more elevated levels of total plasma Hcy, Cys, GSH and Glu-Cys in patients than in controls and also found that Hcy and Cys bound to LDL were significantly increased in nephropathic subjects. By multiple linear regression, we found that in healthy people, total Hcy was the most important determinant of LDL-bound Hcy and Cys-Gly was negatively associated with apoB-Hcy concentrations. In CKD the most important determinant of homocysteinylation was creatinine while total plasma Hcy is weakly associated with apoB-Hcy. The increased levels in Hcy-LDL observed in CKD patients might account, at least in part, for the excess of cardiovascular risk; thus LDL S-homocysteinylation can be considered a key marker of risk for cardiovascular disease in these individuals.


Differential modulation by vanadium pentoxide of the secretion of CXCL8 and CXCL11 chemokines in thyroid cells.
Recently it has been hypothesized that vanadium serves a carcinogenic role in the thyroid. However, to date, no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals following exposure to vanadium. The present study evaluated the effect of vanadium pentoxide (V2O5) on cell viability and proliferation, and chemokine (C‑X‑C motif) ligand (CXCL)8 and CXCL11 secretion in normal thyrocytes. The results demonstrated that V2O5 had no effect on thyroid follicular cell viability and proliferation. However, V2O5 was able to induce the secretion of CXCL8 and CXCL11 chemokines from thyrocytes. Notably, V2O5 synergistically increased the effect of the interferon (IFN)‑γ on CXCL11 secretion. In addition, V2O5 synergistically increased the effect of tumor necrosis factor‑α on CXCL8 secretion, and abolished the inhibitory effect of IFN‑γ. Overall this induction of CXCL8 and CXCL11 secretion may lead to the induction and perpetuation of an inflammatory reaction in the thyroid. Further studies are now required to evaluate thyroid function and nodule development in subjects who are occupationally exposed, or living in polluted areas.


Olanzapine induced tardive dystonia in case of adolescent bipolar disorder.
Atypical antipsychotics are increasingly being associated with neurological side effects. Risperidone, quetiapine, and aripiprazole have been associated with tardive dystonia among other side effects. Similarly, olanzapine has also been associated with this troublesome effect. However, these reports are from cases of nonaffective psychosis, specially schizophrenia. Moreover, the usual age of onset of this neurological side effect has been reported to be in the midthirties or later. We present here a case of tardive dystonia associated with the use of olanzapine in an adolescent girl suffering from bipolar affective disorder. The slight reduction in the severity of the symptoms with the stopping of olanzapine and the reemergence of the full-blown symptoms with the reintroduction of olanzapine, suggest the contributory role of olanzapine.


Assessment of Selected Baseline and Post-PCI Electrocardiographic Parameters as Predictors of Left Ventricular Systolic Dysfunction after a First ST-Segment Elevation Myocardial Infarction.
To assess the performance of ten electrocardiographic (ECG) parameters regarding the prediction of left ventricular systolic dysfunction (LVSD) after a first ST-segment-elevation myocardial infarction (STEMI). We analyzed 249 patients (74.7% males) treated with primary percutaneous coronary intervention (PCI) included into a single-center cohort study. We sought associations between baseline and post-PCI ECG parameters and the presence of LVSD (defined as left ventricular ejection fraction [LVEF] ≤ 40% on echocardiography) 6 months after STEMI. Patients presenting with LVSD (n = 52) had significantly higher values of heart rate, number of leads with ST-segment elevation and pathological Q-waves, as well as total and maximal ST-segment elevation at baseline and directly after PCI compared with patients without LVSD. They also showed a significantly higher prevalence of anterior STEMI and considerably wider QRS complex after PCI, while QRS duration measurement at baseline showed no significant difference. Additionally, patients presenting with LVSD after 6 months showed markedly more severe ischemia on admission, as assessed with the Sclarovsky-Birnbaum ischemia score, smaller reciprocal ST-segment depression at baseline and less profound ST-segment resolution post PCI. In multivariate regression analysis adjusted for demographic, clinical, biochemical and angiographic variables, anterior location of STEMI (OR 17.78; 95% CI 6.45-48.96; p < 0.001), post-PCI QRS duration (OR 1.56; 95% CI 1.22-2.00; p < 0.001) expressed per increments of 10 ms and impaired post-PCI flow in the infarct-related artery (IRA; TIMI 3 vs. <3; OR 0.14; 95% CI 0.04-0.46; p = 0.001) were identified as independent predictors of LVSD (Nagelkerke's pseudo R2 for the logistic regression model = 0.462). Similarly, in multiple regression analysis, anterior location of STEMI, wider post-PCI QRS, higher baseline number of pathological Q-waves and a higher baseline Sclarovsky-Birnbaum ischemia score, together with impaired post-PCI flow in the IRA, higher values of body mass index and glucose concentration on admission were independently associated with lower values of LVEF at 6 months (corrected R2 = 0.448; p < 0.00001). According to our study, baseline and post-PCI ECG parameters are of modest value for the prediction of LVSD occurrence 6 months after a first STEMI.


Radio receptor assay of serum neuroleptic levels in psychiatric patients.
The radioreceptor assay for the measurement of neuroleptic drugs in serum has been used to study the relationship between dose and serum level in schizophrenic patients receiving these drugs. The assay was found to be reproducible and capable of detecting neuroleptics in the sera of patients receiving a range of both oral and depot drugs, with the exception of trifluoperazine spansules. Linear correlations were obtained between daily dose and serum level for each drug both in individual patients on different doses and between patients on a stable dose. Extrapyramidal side effects were related to the serum neuroleptic level within, but not between, patients. The assay may be of use in clinical practice, including the assessment of compliance or poor response to neuroleptics.


Implicit solvent models for flexible protein-protein docking by molecular dynamics simulation.
The suitability of three implicit solvent models for flexible protein-protein docking by procedures using molecular dynamics simulation is investigated. The three models are (i) the generalized Born (GB) model implemented in the program AMBER6.0; (ii) a distance-dependent dielectric (DDD) model; and (iii) a surface area-dependent model that we have parameterized and call the NPSA model. This is a distance-dependent dielectric model modified by neutralizing the ionizable side-chains and adding a surface area-dependent solvation term. These solvent models were first tested in molecular dynamics simulations at 300 K of the native structures of barnase, barstar, segment B1 of protein G, and three WW domains. These protein structures display a range of secondary structure contents and stabilities. Then, to investigate the performance of the implicit solvent models in protein docking, molecular dynamics simulations of barnase/barstar complexation, as well as PIN1 WW domain/peptide complexation, were conducted, starting from separated unbound structures. The simulations show that the NPSA model has significant advantages over the DDD and GB models in maintaining the native structures of the proteins and providing more accurate docked complexes.


Role of prostaglandin E1 in reducing pulmonary vascular resistance in an experimental model of acute lung injury.
To determine the role and efficacy of prostaglandin E1 (PGE1) on the cardiopulmonary derangements induced by glass bead embolism, two studies were performed. In the first study, a dose response of PGE1 was tested in six animals that were first embolized with sufficient glass beads to double the pulmonary artery pressure (PAP). This study demonstrated that PGE1 reduced PAP and cardiac output by a preload-mediated mechanism, as evidenced by a reduction in the right ventricular (RV) end-diastolic segment length, at doses of 15 and 30 ng/kg.min. The second study was performed in two groups of animals, the control group (n = 6), and the treated group (n = 6), which were given PGE1 at 15 ng/kg.min after the PAP had been doubled by glass bead embolism. RV preload was kept constant. This study demonstrated that there was no difference in pulmonary vascular resistance between either the treated group or the control group. There were no other significant differences between the two groups. The results of both of these studies suggest that there is little afterload reducing effect of PGE1 in this model and at these dose ranges. Part of the mechanism of PGE1 that improves pulmonary edema and gas exchange may be the reduction of filtration surface area and hydrostatic pressures in the lungs.


[Immunological aging].
Immune responses decline with age, as assessed by the increasing role of infections in elderly subjects. This decline is, however, very progressive, and usually only clear-cut after 80 years of age. Major difficulties have been encountered to delineate the cellular basis of this immunodeficiency, which is subtle and inconsistent, at the origin of contradictory reports. This is, however, an important challenge in view of the possible therapeutic perspectives of immunotherapy of aged subjects.


[Observation of the invasion of retinoblastoma cells to ocular tissues in vitro].
To study the invasion of retinoblastoma cells to ocular tissues. The SO-Rb50 cells of retinoblastoma and various ocular tissue cells were co-cultured. The morphological change of the SO-Rb50 cells adherent to ocular tissue cells was observed. SO-Rb50 cells can adhere to the various ocular tissues. The adherent ability of SO-Rb50 cell to different ocular tissue cells was different. Tumor cells could be adhesive to keratocyte, scleral fibrocyte, the fibrocyte and the melanocyte of iris and choroid, the epithelial cells of lens, and the astrocyte of optic nerve and grow, but can not be adhesive to the corneal epithelial cell and retinal pigment epithelial cell. We consider that the interactions of tumor cells with host cells, as with extracellular matrix, also play an important role in the selective growth of organ and tissue of tumor cell metastasis. Retinoblastoma cells can not adhere to retinal pigment epithelial cell, which may serve as a barrier to obstruct the invasion of tumor cell to the choroid. Being adherent to the glial cells of optic nerve, tumor cells grow in flat and the shape of tumor cell changes, which may be the cause of tumor cell migrate rapidly and grow in the brain while the optic nerve was invaded by tumor cells.


A business to build.
Under Peter Carter's leadership the RCN has returned to financial stability and increased its credibility as a voice for nurses. Now he is set to grapple with the government's plans for public sector pensions and NHS job cuts.


The provision and use of medical services during the 1991 World Student Games in Sheffield.
This paper describes the provision and use of medical services organized by Sheffield during the World Student Games in 1991. A descriptive study of medical and physio-therapy records, together with minor incident logs and hospital referrals, was carried out. It was found that 571 medical records and 357 physiotherapy records were completed, of which 83 per cent were generated at the Games Village. The majority of patients were competitors, although team officials accounted for a disproportionate number. Most physiotherapy requests were for sports injuries, whereas this was not so for medical cases. Twenty-five per cent of medical records and 40 per cent of physiotherapy records were for recurrent conditions which had started before arrival. Athletics and football accounted for the greatest number of records per competitor. During the Games, 82 patients were referred to hospital, of whom only 12 were admitted. The largest group of hospital referrals was for dental treatment, and the next largest was for minor trauma. A total of 1089 minor incidents were recorded, mainly at the competition venues and in the Physiotherapy Room at the Games Village. In addition, the Red Cross and the St John Ambulance Association attended to 330 people during the Games. The smallest national teams tended to make most demands on services, probably because the larger teams were accompanied by their own medical and physiotherapy staff. It is concluded that the main demands for medical services at the World Student Games were for general practice and physiotherapy at the Games Village, and for first aid at competition venues.(ABSTRACT TRUNCATED AT 250 WORDS)


Granzyme B gene polymorphisms, colorectal cancer risk, and metastasis.
The human granzyme B protein (GrB), which is encoded by granzyme B gene (GZMB), plays a major role in eliminating cancer cells. Polymorphisms of GZMB gene such as Q55R, P94A, and Y247H have been shown to affect GrB activity and the subsequent cancer risk. In this study, we examined possible association between GZMB gene polymorphisms and susceptibility to colorectal cancer (CRC). In addition, the contribution of the examined polymorphisms to colorectal cancer metastasis to lymph node and distant organ was investigated. A total of 50 venous blood samples collected from CRC patients were analyzed to identify the Q55R, P94A, and Y247H polymorphisms. As a control group, 20 healthy subjects were enrolled in the study. The Q55R, P94A, and Y247H polymorphisms were genotyped by polymerase chain reaction and sequencing method. Data analysis was carried out using the statistical package SPSS version 17 to compute all descriptive statistics. Chi-square and Fisher exact tests (if the expected value in any cell is less than 5) were used to evaluate the genotype distribution and allele frequencies of the studied polymorphism. The results revealed that the distribution of Q55R, P94A, and Y247H are not significantly different in CRC patients compared to the controls. In addition, no association between Q55R, P94A, and Y247H polymorphisms and its metastasis to lymph node and distant organ was detected. These results suggest that GZMB Q55R, P94A, and Y247H polymorphisms are not significantly associated with colon cancer incidence, or metastasis to lymph node and distant organ. However, this study was limited by its relatively small sample size; thus, to confirm current findings, a bigger multicenter design study is warranted.


[Digital processing and evaluation of ultrasound images].
With the help of workstations and PCs, on-site image processing has become possible. If the images are not available in digital form the video signal has to be A/D converted. In the case of colour images the colour channels R (red), G (green) and B (blue) have to be digitized separately. "Truecolour" imaging calls for an 8 bit resolution per channel, leading to 24 bits per pixel. Out of a pool of 2(24) possible values only the relevant 128 gray values and 64 shades of red and blue respectively needed for a colour-coded ultrasound image have to be isolated. Digital images can be changed and evaluated with the help of readily available image evaluation programmes. It is mandatory that during image manipulation the gray scale and colour pixels and LUTs (Look-Up-Table) must be worked on separately. Using relatively simple LUT manipulations astonishing image improvements are possible. Application of simple mathematical operations can lead to completely new clinical results. For example, by subtracting two consecutive colour flow images in time and special LUT operations, local acceleration of blood flow can be visualized (Colour Acceleration Imaging).


Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses.
Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers. Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses. For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a strong predictor for primary stroke.


Prevalence, molecular detection, and virulence gene profiles of Campylobacter species in humans and foods of animal origin.
Campylobacteriosis is one of the most well-characterized bacterial foodborne infections worldwide that arise chiefly due to the consumption of foods of animal origin such as poultry, milk, and their products. The disease is caused by numerous species within the genus Campylobacter, but Campylobacter jejuni is the most commonly isolated species from established cases of human campylobacteriosis. This study was conducted to determine the prevalence and virulence of Campylobacter isolates from human, chicken, and milk and milk products in Egypt. A total of 1299 samples (547 chicken intestine and liver, 647 milk and milk products, and 105 human stool) were collected and microbiologically investigated, confirmed by multiplex polymerase chain reaction (PCR) targeting the 23S rRNA, hipO, and glyA genes specific for Campylobacter spp., C. jejuni, and Campylobacter Coli, respectively, followed by virulence genes (Campylobacter adhesion to fibronectin F [cadF] and cdtB) detection using PCR. About 38.09%, 37.84%, and 8.5% of human stool, chicken, and milk and milk product samples, respectively, were bacteriologically positive, with a total of 302 Campylobacter isolates. All isolates were molecularly confirmed as Campylobacter spp. (100%) where 285 isolates (94.37%) were identified as C. jejuni and 17 isolates (5.62%) as C. coli. Regarding the virulence pattern, all isolates (100%) carried cadF gene while cytolethal distending toxin B gene was definite in 284/302 isolates (94%), concisely, 282/285 (98.94%) C. jejuni isolates, and in 2/17 (11.76%) C. coli isolates. The widespread presence of these highly virulent Campylobacter, especially C. jejuni, proofs the urgent need for the implementation of stringent control, public health, and food protection strategies to protect consumers from this zoonotic pathogen. The availability of information about pathogen virulence will enable enhanced local policy drafting by food safety and public health officials.


Disease outcomes as a consequence of environmental influences on the development of the immune system.
To review recent studies on disease outcomes as a consequence of environmental influences on the developing immune system early in life. The increasing incidence of 'immunologically mediated disease of affluence', such as allergies, type I diabetes and inflammatory bowel disease (IBD), suggests that they are consequences of common environmental factors. No such factors have been identified, however, and prospective studies fail to support commonly given advice. Interest has, therefore, switched towards factors that could induce and maintain tolerance to allergens and autoantigens. A unifying link between Th1-dependent autoimmune disease and Th2-linked atopic allergy would be a disturbed immune regulation involving T regulatory cells. Microbial colonization of the gastrointestinal tract, linked with lifestyle, may be an important determinant. Several prospective, controlled studies, in which different strains of Lactobacillus were given to pregnant mothers and then to their newborn babies for 6-12 months, have shown a modest reduction of immunoglobulin E (IgE)-mediated eczema in infants. Currently, there is poor support for giving any particular allergy-preventive advice. Novel potential strategies to enhance immune regulation and tolerance induction include modulation of gut microbiota, for example, by probiotics and prebiotics. Although the results are somewhat encouraging, they are insufficient to base general recommendations on, however.


Uterine Torsion in an Elderly Woman Associated with Leiomyoma and Continuously Elevating Muscle Enzymes: A Case Study and Review of Literature.
Uterine torsion is extremely rare in postmenopausal women. Total ischemia of the uterus may cause life-threatening conditions; hence, accurate diagnosis and surgical intervention are crucial. However, preoperative diagnosis is often challenging due to nonspecific clinical features and laboratory findings. We report a case of uterine torsion in a 73-year-old woman who presented with mild but gradually worsening intermittent abdominal pain. During a 5-day observation, repeated blood exams showed elevating serum muscle enzyme levels, lactate dehydrogenase (LDH), and creatinine kinase (CPK), in addition to nonspecific signs of inflammation. Computed tomography (CT) scans were obtained before and after the worsening of symptoms, which revealed changes in size and position of the enlarged uterus with a large leiomyoma, even within a 5-day interval. Based on these findings, the preoperative diagnosis was uterine torsion. Emergency surgery revealed a 540-degree torsion of the uterus at the cervix and uterine body junction. Total hysterectomy and bilateral salpingo-oophorectomy were performed. Plasma muscle enzyme levels normalized after surgery, and the patient recovered without complications. In conclusion, uterine torsion should be considered during differential diagnosis in elderly women with large leiomyoma, even when symptoms are mild. Elevating plasma muscle enzymes may be an indication of uterine torsion; hence, repeated laboratory works and CT scanning should be performed when symptoms progress. Comparison of CT images, taken before and after the worsening of symptoms, may also be relevant for diagnosis. Since uterine torsion may cause rapid deterioration and become life-threatening, early diagnosis and surgical intervention are crucial to avoid serious complications.


Long-Term Clinical Outcomes of Unprotected Left Main Percutaneous Coronary Intervention: A Large Single-Centre Experience.
This study sought to report the 10-year clinical outcomes of patients who underwent unprotected left main (LM) percutaneous coronary intervention (PCI) in a large centre. A total of 913 consecutive patients who underwent unprotected LM PCI from January 2004 to December 2008 at Fu Wai Hospital were retrospectively analysed; the mean age was 60.0 ± 10.9 years, females accounted for 22% of patients, diabetes was present in 27.7% of patients, and an LM bifurcation lesion occurred in 82.9% of patients. During the median follow-up of 9.7 years, major adverse cardiac or cerebrovascular events (MACCEs) occurred in 25.6% (234) of patients, and the rates of all-cause death, myocardial infarction, and stroke were 14.9%, 11.0%, and 7.1%, respectively. Cardiac death occurred in only 7.9% of patients. The estimated event rate was 41.9% for death/myocardial infarction/any revascularization and 45.9% for death/MI/stroke/any revascularization. Definite/probable stent thrombosis occurred in 4.3% (39) of patients. According to the subgroup analysis, IVUS-guided PCI was associated with less long-term MACCEs. Further multivariate analysis identified that age and LVEF<40% were the only independent predictors for 10-year death. Age, LVEF<40%, creatinine clearance, and incomplete revascularization were independent predictors for death/MI, while a two-stent strategy, diabetes, a transradial approach, and the use of bare metal stents (BMSs) or first-generation drug-eluting stents (DESs) were not. Unprotected LM PCI in a large cohort of consecutive patients in a single large centre demonstrated favourable long-term outcomes up to 10 years even with the use of BMSs and first-generation of DESs.


[Bloodstream infections in cancer patients].
Bloodstream infections (BI) are an important cause of morbidity and mortality in cancer patients. A retrospective study was performed in two hospitals aimed to evaluate characteristics of BI episodes occurred in adult patients with hematologic (HN) and solid (SN) neoplasia other than non-melanoma skin cancers in the period 2009-2016. A total of 467 episodes of bacteremia and 16 of fungemia were identified. A total of 200 (41.4%) bacteremias occurred in patients with HN and 283 (58.6%) in patients with SN. The most frequent SN and HN were colon cancer (18.7%) and non-Hodgkin lymphoma (27%), respectively. The main risk factors for BI were a previous surgical procedure in SN and chemotherapy in the previous 30 days and use of central venous catheter in HN. Infections were mainly acquired in the hospital environment and the most frequent presentation was bacteremia without focus, mostly in HN (38% vs. 20.8%, p < 0.001). Gram negative bacilli (GNB) were isolated in 336 (69.5%) episodes and predominated over Gram positive cocci (GPC) in both groups. Escherichia coli was the most frequent GNB isolated in both SN (24.7%) and HN patients (20.5%). The most frequent GPC was Staphylococcus aureus. Multidrug-resistance was found in 15% of the isolates in SN and 18% in HN. The overall mortality was 40.5% in patients with HN and 37.5% in patients with SN, with the majority of deaths occurring in the first 30 days.


Relationship of fetal growth to duration of heat stress in an ovine model of placental insufficiency.
Intrauterine growth restriction in an ovine model occurs after exposure to environmental heat stress for 80 days beginning at 35 days' gestation. Our objective was to determine whether intrauterine growth restriction is reversible on removal of the heat stress after only 55 days of exposure; that is, does a brief exposure at a critical point of development suffice? Five pregnant ewes were exposed to heat stress beginning at 35 days' gestation and were removed after 55 days of exposure. Five ewes in a control group were studied as contemporaneous controls and added to data from 37 ewes in a control group previously studied. Serial fetal biometric ultrasonographic measurements (biparietal diameter, abdominal circumference, femur length, and tibia length) were obtained beginning at 50 days' gestation. Growth curves were calculated for each parameter, and comparisons were made between fetuses in the group exposed to heat stress for 55 days and 42 fetuses in the control group and 4 fetuses from a previous study that were exposed to heat for 80 days. Regression lines, 95% confidence intervals, and slopes were determined for each study group. Both the 55-day and the 80-day heat exposure groups showed a significant reduction in fetal and placental weights compared with the control group. Animals in the 80-day group had significantly lower fetal and placental weights than the animals in the 55-day group (P <.05). Indexes of somatic growth (abdominal circumference, femur length, and tibia length) for the control group were significantly greater than those of either the 55-day group or the 80-day group (P <.001). Asymmetric growth restriction was evident in both heat groups by a biparietal diameter/abdominal circumference ratio that was significantly higher than in the control group (P <.004 for the 55-day group and P <.001 for the 80-day group). The slopes for somatic parameters (abdominal circumference, femur length, and tibia length) versus time became significantly different between the control and 55-day groups at 77, 101, and 80 days' gestation, respectively. The 55-day group had abdominal circumference and femur length measurements that were significantly greater than those in the 80-day group. The fetuses in the 55-day and 80-day groups reflect a pattern of asymmetric intrauterine growth restriction. Our findings suggest that the initial insult affecting fetal and placental growth occurs early in gestation, but removal of fetuses after only 55 days of exposure significantly reduces the degree of fetal growth restriction compared with that found in those fetuses exposed for 80 days.


Quantitative assessment of right ventricular structural abnormalities by right ventricular polar mapping of single photon emission computed tomogram.
The identification of right ventricular (RV) abnormalities is clinically important in the evaluation of arrhythmogenic substrates in right ventricular-originated ventricular tachycardia (RVT). The purpose of this study was to determine the diagnostic benefit of quantitative analysis in RV single photon emission computed tomography (SPECT) imaging with (99m)Tc-tetrofosmin/sestamibi in patients with RVT. Thirty patients with RVT (15 with idiopathic RVT and 15 with arrhythmogenic right ventricular cardiomyopathy (ARVC)) were compared with 27 control subjects (including 11 with right bundle branch block) with regard to the semiquantitative RV uptake score in each of six segments and the quantitative RV extent score in polar coordinate map displays by SPECT imaging. The RV total score and RV extent score were compared with the RV global function. Perfusion abnormalities were more frequently detected (P = 0.0001) in the ARVC group (59/90, 65.6%) than in the idiopathic RVT group (4/90, 4.4%) or controls (1/162, 0.6%). The RV extent score in the ARVC group (53.0 +/- 24.8) was significantly higher than that in the idiopathic RVT group (8.4 +/- 10.1) or controls (1.2 +/- 4.9). The RV extent score correlated well with the regional RV perfusion score (P < 0.0001) and with the RV ejection fraction (P < 0.0001). Non-invasive RV perfusion mapping using a (99m)Tc-labelled tracer is useful for the quantitative evaluation of RV substrates in patients with ARVC.


Nuclear localization of mitogen-activated protein kinase kinase 1 (MKK1) is promoted by serum stimulation and G2-M progression. Requirement for phosphorylation at the activation lip and signaling downstream of MKK.
Stimulation of mammalian cells results in subcellular relocalization of Ras pathway enzymes, in which extracellular signal-regulated protein kinases rapidly translocate to nuclei. In this study, we define conditions for nuclear localization of mitogen-activated protein kinase kinase 1 (MKK1) by examining effects of perturbing the nuclear export signal (NES), the regulatory phosphorylation sites Ser218 and Ser222, and a regulatory domain at the N terminus. After disrupting the NES (Delta32-37), nuclear uptake of MKK was enhanced when quiescent cells were activated with serum-phorbol 12-myristate 13-acetate or BXB-Raf-1 cotransfection. Uptake was enhanced by mutation of Ser218 and Ser222 to Glu and Asp, respectively, and blocked by mutation of these residues to Ala, although mutation of Lys97 to Met, which renders MKK catalytically inactive, did not interfere with uptake. Therefore, nuclear uptake of MKK requires incorporation of phosphate or negatively charged residues at the activation lip but not enzyme activity. On the other hand, uptake of an active MKK mutant with disrupted NES (Delta32-51) was elevated in quiescent as well as stimulated cells, and pretreatment of cells with the MKK inhibitor 1,4-diamino-2, 3-dicyano-1,4-bis[2-aminophenylthio]butadiene blocked nuclear uptake. Thus, signaling downstream of MKK is also necessary for translocation. Finally, wild type MKK containing an intact NES translocates to nuclei during mitosis before envelope breakdown. Comparison of mutants with Ser to Glu and Asp or Ala substitutions indicates that Ser phosphorylation is also required for mitotic nuclear uptake of MKK.


The 2-stage hypospadias repair. Is it a misnomer?
The repair of penoscrotal or perineal hypospadias with severe chordee may require division of the urethral plate to facilitate repair. While a 2-stage approach to these difficult cases has been advocated, we have used a modified tubularized transverse preputial island flap (TPIF) repair as a 1-stage procedure. We compare our results with both procedures. Between 1997 and 2001, 1 surgeon (DAC) performed 22 penoscrotal or scrotal hypospadias repairs that required transection of the urethral plate. A TPIF or planned 2-stage repair was done in 12 and 10 boys, respectively. The TPIF was modified by suturing the medial edge of the island flap along the length of the corpora recreating a urethral plate and then tubularizing a neourethra. The 2-stage approach consisted first of mobilizing skin to the ventrum of the penis followed 6 to 12 months later by a urethroplasty. At followup cosmetic and functional results were assessed. The TPIF and staged repair groups have been followed for a mean 24.5 and 43.5 months following the first repair, respectively. Of the 12 boys undergoing a TPIF 2 (16.7%) required a fistula repair or meatoplasty while 7 of 10 (70%) required at least 1 additional operation after the stage 2 urethroplasty (p <0.05). A mean of 1.6 additional repairs following the stage 2 urethroplasty was required. At last followup physical examination demonstrated a straight penis with distal meatus in 19 of 22 boys. Persistent complications include a concealed penis and recurrent fistula in 2 boys following a staged repair and glanular separation in 1 boy following TPIF. In our experience the staged approach to the repair of severe hypospadias requires significantly more cumulative surgical attempts than the modified TPIF. Indeed, in the majority of our cases the so-called "2-stage hypospadias repair" was a misnomer. The TPIF offers a reliable 1-stage repair. We prefer this approach to staged repairs even for severe hypospadias.


Evidence supporting surgery as treatment of choice for acromegaly.
Within a period of fourteen years 531 operations for growth hormone (GH)-secreting adenomas were carried out. In this consecutive series 73% of the 396 patients who underwent primary transsphenoidal surgery achieved basal GH levels below 5 micrograms/l, and 58% also had an adequate suppression following an oral glucose tolerance test (OGTT). Slightly less favourable results were found in patients requiring surgery following an initial therapy. However, 41% of 121 such patients, who had either been operated upon previously or who had received external or internal irradiation, nevertheless achieved basal GH levels below 5 micrograms/l after the surgical reintervention. Normal suppression of serum GH during an OGTT was observed in 23% of these patients. The overall complication rate was low and tumour recurrences were very rare. To facilitate easier tumour removal, octreotide was preoperatively administered in 53 patients undergoing primary surgery of large adenomas. Recurrences were documented in a few exceptional cases. These data support our previous experience that once a normal suppression of growth hormone has been documented following surgery of pituitary adenomas, the long-term outcome is favourable.


Metabolic Strategies for Inhibiting Cancer Development.
The tumor microenvironment is a complex mix of cancerous and noncancerous cells (especially immune cells and fibroblasts) with distinct metabolisms. These cells interact with each other and are influenced by the metabolic disorders of the host. In this review, we discuss how metabolic pathways that sustain biosynthesis in cancer cells could be targeted to increase the effectiveness of cancer therapies by limiting the nutrient uptake of the cell, inactivating metabolic enzymes (key regulatory ones or those linked to cell cycle progression), and inhibiting ATP production to induce cell death. Furthermore, we describe how the microenvironment could be targeted to activate the immune response by redirecting nutrients toward cytotoxic immune cells or inhibiting the release of waste products by cancer cells that stimulate immunosuppressive cells. We also examine metabolic disorders in the host that could be targeted to inhibit cancer development. To create future personalized therapies for targeting each cancer tumor, novel techniques must be developed, such as new tracers for positron emission tomography/computed tomography scan and immunohistochemical markers to characterize the metabolic phenotype of cancer cells and their microenvironment. Pending personalized strategies that specifically target all metabolic components of cancer development in a patient, simple metabolic interventions could be tested in clinical trials in combination with standard cancer therapies, such as short cycles of fasting or the administration of sodium citrate or weakly toxic compounds (such as curcumin, metformin, lipoic acid) that target autophagy and biosynthetic or signaling pathways.


Defining Anastomotic Leak and the Clinical Relevance of Leaks.
Surgeons universally dread gastrointestinal anastomotic leaks, yet the precise definition is not widely agreed on despite international consensus guidelines. Likewise, leaks are not uniformly reported which makes comparisons across studies flawed. Leak rates range from 1 to 3% for ileocolonic, 0.5 to 18% for colorectal, and 5 to 19% for coloanal anastomoses. The sequelae of an anastomotic leak vary but generally correlate with the need for a change in clinical management, from minimal changes to the need for reoperation. Short- and long-term outcomes can be life-altering or life-threatening. Temporary or permanent stomas may be necessary and low pelvic anastomotic leaks may affect bowel function. For cancer patients, leaks can delay treatment and negatively affect oncologic outcomes. In Crohn's patients, leaks are associated with higher recurrence rates. In essence, the lack of agreement on the definition of an anastomotic leak inhibits meaningful understand of its epidemiology, prevention, and treatment.


Safety of bronchoscopy, biopsy, and BAL in research patients with COPD.
Bronchoscopy with biopsy and BAL is being performed increasingly in patients with COPD as a research tool. Previous reports have shown these procedures to be safe in asthmatic patients, but there is little safety data specific to COPD. We studied 57 patients with COPD (11 women and 46 men; median FEV(1), 1.2 L [range, 0.64 to 2.69 L]; percent predicted FEV(1), 44.5% [range, 25 to 74.8%]). Eleven patients had mild disease, 28 patients had moderate disease, and 18 patients had severe disease according to British Thoracic Society classification. Ninety-eight bronchoscopies were performed according to American Thoracic Society guidelines: 68 procedures with endobronchial biopsy and BAL and 30 procedures with biopsy alone. Controlled oxygen was administered via nasal cannula, and pulse oximetry and vital signs were monitored. Five adverse events occurred. One patient in the moderate-disease group had severe bronchospasm requiring 4 days of inpatient treatment. One patient in the severe-disease group had a pneumothorax requiring 7 days of inpatient treatment. There were three episodes of hemoptysis, two with pleuritic pain (in the BAL group) that settled without intervention. No deaths or prolonged morbidity were observed. We found a 2.0% incidence of adverse events requiring hospital treatment and a 3.1% incidence of minor hemoptysis requiring no intervention. Bronchoscopy, biopsy, and BAL can be performed safely in patients with COPD, including those with severe disease, provided careful assessment is performed and guidelines are adhered to.


Commentary: schizophrenic patients.
The results of the Boston Psychotherapy of Schizophrenia Study were reported with a mixture of hopes and fears (Gunderson et al. 1984; Stanton et al. 1984). The hope was that those therapists, hospitals, and training programs that promoted and promulgated the idea that an exploratory, insight-oriented (EIO) psychotherapy was an important, usual, and practical way of treating schizophrenia would step back from this claim and see this approach in a more restricted and selective perspective. The fear was that the results would be reduced to a broader indictment of this modality such that its proper role with schizophrenic patients would be buried. Behind both this wish and this fear were the types of vivid personal experience in working with schizophrenic patients that the papers by Sandin and by Levander and Cullberg illustrate.


Improved bioavailability of para-boronophenylalanine by cyclodextrin complexation.
This study was undertaken to develop an oral dosage form for para-boronophenylalanine (BPA) plus cyclodextrin (CD) for use in the thermal neutron capture therapy for malignant melanoma. Powders of the BPA and CD complexes were obtained in a molar ratio of 1:2. X-ray diffraction of the BPA-CD complexes showed halo patterns that indicated that each complex was in a new solid state as an amorphous compound. The enhancement of BPA solubility by glucosyl (G1)- and maltosyl (G2)-alpha-CD was greater than that with the other CDs. The isolation rate of BPA from its complex was different for each BPA-CD complex. The bioavailability of BPA in rats was improved with oral administration of the BPA-alpha-CD, G1-alpha-CD, and G2-alpha-CD complexes. In contrast, a complex of BPA and dimaltosyl (G2G2) or G2-beta-CD, which had low release rate and low solubility, did not improve the bioavailability of BPA. These results indicate that the solubility and release rate of BPA from a complex in solution are important for the bioavailability of BPA after oral administration of BPA-CD complexes.


Effects of Tnt1 tobacco retrotransposon insertion on target gene transcription.
The effects of Tnt1 retrotransposon insertion on nitrate reductase (NR) gene transcription have been analyzed in three NR-deficient insertional, mutants of Nicotiana tabacum. In the three mutants, named h9-Nia4, h9-Nia5 and h9-Nia6, Tnt1 was inserted into exon 3, exon 2 and exon 1 of the nia2 NR alloallelle, respectively. The mutants h9-Nia4 and h9-Nia6, which contained Tnt1 insertions that were oriented opposite to the direction of nia2 gene transcription, expressed chimaeric nia2-Tnt1 RNAs, respectively 12 kb and 10 kb long. The size observed in h9-Nia6 was close to the expected size for a full-length hybrid transcript starting and ending under the control of nia2 signals (about 9 kb). The larger transcript found in h9-Nia4 was shown to be due to a failure to splice the nia2 intron 2. The mutant h9-Nia5, which contained a Tnt1 insertion oriented in parallel with the direction of nia2 transcription expressed two truncated nia2-Tnt1 RNAs, 2 kb and 6.7 kb long. These transcripts arose from termination in the long terminal repeats (LTRs) of Tnt1. Since no full-length hybrid RNA was detected, we suggest that Tnt1 carries efficient termination signals, which are more efficiently recognized in the 3' LTR than in the 5' LTR.


Red cell survival: relevance and mechanism involved.
Red blood cells (RBCs) often have a short circulating half-life in hemodialysis patients, which increases the difficulty of achieving a stable hemoglobin level. Fluctuations in erythropoietin (EPO) levels contribute to this increased RBC turnover because a decline in the level of EPO triggers the preferential destruction of newly-formed RBC, a process termed neocytolysis. The RBCs that are released during the treatment of renal anemia are often hypochromic, with a low content of iron; these RBCs are vulnerable to rapid turnover because iron-deficiency affects RBCs in several ways, such as, increased exposure of the phagocytic signaling molecule phosphatidylserine, loss of deformability, and increased oxidative stress. Both EPO fluctuation and the release of iron-deficient RBCs are characteristic events occurring during the management of renal anemia, and the shorter RBC lifetime is a component of the large fluctuations in hemoglobin level seen in patients on hemodialysis.


A survey of home nursing services in Taiwan.
This study investigated the current situation of home nursing services in Taiwan. A total of 93 home nursing agencies (response rate of 75%) responded to a mail survey. The majority of the agencies (63%) had been established within the last 3 years before the survey, were hospital-based (90%), and had less than 60 (89.3%) average total number of visits per month per nurse. Most of the home care nurses had taken home care nursing training courses and had at least 2 years of clinical experience. Half of the agencies provided care for patients on a respirator, and 28% provided in-home hospice care. Almost a third of the agencies performed poorly in the areas of supply management, supervision of home visits, and quality monitoring and improvement mechanisms. Several suggestions for the development of home nursing services in Taiwan are made.


Evolution at two time frames: ancient structural variants involved in post-glacial divergence of the European plaice (Pleuronectes platessa).
Changing environmental conditions can lead to population diversification through differential selection on standing genetic variation. Structural variant (SV) polymorphisms provide examples of ancient alleles that in time become associated with novel environmental gradients. The European plaice (Pleuronectes platessa) is a marine flatfish showing large allele-frequency differences at two putative SVs associated with environmental variation. In this study, we explored the contribution of these SVs to population structure across the North East Atlantic. We compared genome-wide population structure using sets of RAD-sequencing SNPs with the spatial structure of the SVs. We found that in contrast to the rest of the genome, the SVs were only weakly associated with an isolation-by-distance pattern. Indeed, both SVs showed important variation in haplogroup frequencies, with the same haplogroup increasing both along the salinity gradient of the Baltic Sea, and found in high frequency in the northern-range margin of the Atlantic. Phylogenetic analyses suggested that the SV alleles are much older than the age of the Baltic Sea itself. These results suggest that the SVs are older than the age of the environmental gradients with which they currently co-vary. Altogether, our results suggest that the plaice SVs were shaped by evolutionary processes occurring at two time frames, firstly following their origin, ancient spread and maintenance in the ancestral populations, and secondly related to their current association with more recently formed environmental gradients such as those found in the North Sea-Baltic Sea transition zone.


The EC night-time repressor plays a crucial role in modulating circadian clock transcriptional circuitry by conservatively double-checking both warm-night and night-time-light signals in a synergistic manner in Arabidopsis thaliana.
During the last decade, significant research progress has been made in Arabidopsis thaliana in defining the molecular mechanisms behind the plant circadian clock. The circadian clock must have the ability to integrate both external light and ambient temperature signals into its transcriptional circuitry to regulate its function properly. We previously showed that transcription of a set of clock genes including LUX (LUX ARRHYTHMO), GI (GIGANTEA), LNK1 (NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED GENE 1), PRR9 (PSEUDO-RESPONSE REGULATOR 9) and PRR7 is commonly regulated through the evening complex (EC) night-time repressor in response to both moderate changes in temperature (Δ6°C) and differences in steady-state growth-compatible temperature (16-28°C). Here, we further show that a night-time-light signal also feeds into the circadian clock transcriptional circuitry through the EC night-time repressor, so that the same set of EC target genes is up-regulated in response to a night-time-light pulse. This light-induced event is dependent on phytochromes, but not cryptochromes. Interestingly, both the warm-night and night-time-light signals negatively modulate the activity of the EC night-time repressor in a synergistic manner. In other words, an exponential burst of transcription of the EC target genes is observed only when these signals are simultaneously fed into the repressor. Taken together, we propose that the EC night-time repressor plays a crucial role in modulating the clock transcriptional circuitry to keep track properly of seasonal changes in photo- and thermal cycles by conservatively double-checking the external light and ambient temperature signals.


Segmental body composition transitions in stroke patients: Trunks are different from extremities and strokes are as important as hemiparesis.
Loss of muscle and bone mass is prevalent in the stroke population. Few studies have investigated the difference between having a stroke and hemiplegia and their influence on segmental body composition. This study aimed to evaluate the changes of body composition in the extremities and trunk of stroke patients in comparison with those of the healthy controls. Stroke patients with an onset of longer than 6 months and healthy participants matched by age and gender were recruited. Body weight, height, grip strength, and gait speed were measured, and a dual-energy x-ray absorptiometry was used to evaluate body composition. The generalized estimation equation model was employed to explore factors influencing extremity body composition, whereas those influencing the trunk body composition were analyzed using the general linear model. The study included 37 stroke patients and 37 healthy controls. The stroke group had significantly slower gait speeds, weaker hand grip strength, and a lower skeletal muscle index than the controls. Using 7.0 kg/m2 for men and 5.14 kg/m2 for women as the cutoff value for the skeletal muscle index, the prevalence of sarcopenia in our stroke group was found to be 48.6% (18/37). Being a stroke patient was associated with a decrease in bone (β = -21.89 g, p = 0.001) and lean mass (β = -210.46 g, p = 0.031) of the upper extremity and bone mass (β = -39.28 g, p = 0.008) of the lower extremity, regardless of the presence of limb paralysis. The limbs on the hemiplegic side had a further decline of extremity bone and lean mass. The stroke patients had an increase in trunk fat mass (β = 1392.68 g, p = 0.004) but not that of the extremities. Having a stroke and hemiparesis are both associated with body composition changes of the extremities, especially for bone and lean mass. A stroke is likely to increase the fat mass of the trunk rather than that of the extremities. A future cohort study is needed to clarify the causal relationship between stroke and transition of body composition and to investigate whether these changes are related to the disease prognosis or can be reversed by exercise and nutritional support.


Effects of Er:YAG laser irradiation and manipulation treatments on dentin components, part 1: Fourier transform-Raman study.
The effects of laser etching, decontamination, and storage treatments on dentin components were studied using Fourier transform (FT)-Raman spectroscopy. Thirty bovine incisors were prepared to expose the dentin surface and then divided in two main groups based upon the decontamination process and storage procedure: autoclaved (group A, n=15) or stored in thymol aqueous solution (group B, n=15). The surfaces of the dentin slices were schematically divided into four areas, with each one corresponding to a treatment subgroup. The specimens were either etched with phosphoric acid (control subgroup) or irradiated with erbium-doped yttrium-aluminum-garnet (Er:YAG) laser (subgroups: I-80 mJ, II-120 mJ, and III-180 mJ, and total energy of 12 J). Samples were analyzed by FT-Raman spectroscopy; we collected three spectra for each area (before and after treatment). The integrated areas of five Raman peaks were calculated to yield average spectra. The areas of the peaks associated with phosphate content (P<0.001), type I collagen, and organic C-H bonds (P<0.05) were reduced significantly in group A (control). Analyses of samples irradiated with reduced laser energies did not show significant changes in the dentin components. These results suggest that thymol storage treatment is advised for in vitro study; furthermore, 12 J of Er:YAG laser energy does not affect dentin components.


Role of muscles in lumbar spine stability in maximum extension efforts.
Many problems of the lumbar spine that cause pain are attributed to instability. The ligamentous spine (without muscles) is unstable at very low compressive loads. This study examined the hypothesis that instability of the lumbar spine is prevented under normal circumstances by the stiffness of spinal musculature, without active responses from the neuromuscular control system. The effect of muscle activity (force and stiffness) on the stability of the lumbar spine was analyzed for maximum voluntary extension efforts with different spinal postures in the sagittal plane. The analysis included realistic three-dimensional representation of the muscular anatomy with muscles crossing several motion segments. The stiffness of motion segments was represented using in vitro measured properties. Under a range of conditions with maximum extension effort, active muscle stiffness was required to prevent the lumbar spine from buckling. The dimensionless value of the muscle stiffness parameter q as a function of activation and length had to be greater than a critical value in the range of 3.7-4.7 in order to stabilize the spine. Experimentally determined values of q ranged from 0.5 to 42. These analyses demonstrate how changes in motion segment stiffness, muscle activation strategy, or muscle stiffness (due to degenerative changes, injuries, fatigue, and so on) might lead to spinal instability and "self-injury."


Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil.
The aim of this study was to unravel the mechanisms responsible for the increased risk of gall stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride lowering therapy by bezafibrate and fish oil on determinants of cholelithiasis (biliary lipid composition and gall bladder motility) in HTG patients. Gall bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between nine HTG patients and 10 age, sex, and body mass index matched normolipidaemic controls. The effects of bezafibrate and fish oil in HTG patients were studied in a randomised cross over trial. HTG patients showed 14-fold higher serum triglyceride (TG) levels than controls. Biliary lipid composition, fasting gall bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p<0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68% and -51% v baseline, respectively; both p<0.01). Fasting CCK levels were not affected whereas CCK induced gall bladder emptying increased during bezafibrate (+29%; p<0.001) and tended to increase on fish oil therapy (+13%; p=0.07). Postprandial gall bladder motility improved on bezafibrate and fish oil (+47 and +25% v baseline, respectively; both p<0.02) at least partly due to increased gall bladder sensitivity to CCK (both p<0.05 v baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p</=0.05) but no effects on cholesterol saturation index were seen with either treatment. We suggest that impaired gall bladder motility occurs in HTG patients due to decreased sensitivity to CCK, which may add to the enhanced risk of gall stone disease in HTG patients. Triglyceride lowering therapy by both fish oil and bezafibrate improve gall bladder dysmotility without adversely affecting biliary cholesterol saturation.


Hyperplastic (metaplastic) polyps of the colon. A histologic and histochemical study.
One hundred seventy-three hyperplastic polyps removed from the colon of 146 patients were carefully examined by light microscopy in order to evaluate the histologic variants. Seventy polyps were also studied histochemically in order to assess the mucin distribution. Seven polyps measured greater than 1 cm. The frequency of hyperplastic foci has been assessed in a review of 1000 colonic adenomas, 50 juvenile, 30 inflammatory, and six Peutz-Jeghers polyps. The vast majority of the hyperplastic polyps showed features similar to those of inflammatory and ischemic bowel mucosa, leading to the suggestion of an inflammatory-ischemic origin of the polyps. The frequent finding of dysplastic features within hyperplastic polyps greater than 1 cm suggests that at least the large polyps are dysplasia-prone.


How Satisfied Are Patients With Their Radiologists? Assessment Using a National Patient Ratings Website.
The purpose of this study is to assess features of patient satisfaction scores for U.S. radiologists using a popular physician rating website. Patient reviews were retrieved from the website RateMDs for all listed radiologists in all 297 U.S. cities with population 100,000 or greater. Reviews included rating scores of 1-5 (5 = highest) in four categories (staff, punctuality, knowledge, and helpfulness). Additional physician information was obtained from Medicare files. Common words in patient free-text comments were assessed. Statistical analyses were performed. We identified 1891 patient reviews for 1259 radiologists. In all four categories, the most common score was 5 for excellent (62.7-74.3%), and the second most common score was 1 for terrible (13.5-20.4%); scores of 2-4 were far less frequent (1.9-11.6%). Scores for all four categories highly correlated with one another (r = 0.781-0.951). Radiologists in the Northeast scored significantly lower (p < 0.001) than those elsewhere for both staff and punctuality. Radiologists attending a designated top 50 medical school showed nonsignificant trends toward lower scores for helpfulness (p = 0.073) and knowledge (p = 0.062). The most common words in free-text comments for positive reviews were "caring," "knowledgeable," and "professional." For negative reviews, "rude," "pain," and "unprofessional" were most common. Overall, most radiologists rated online by their patients score well, but reviews tended to be either strongly positive or negative. Scores across various categories are highly correlated, suggesting that there is a halo effect. Radiologists should recognize the effect of both facility- and radiologist-related factors in influencing patients' overall perceptions.


Novel neogala-series glycosphingolipids with terminal mannose and glucose residues from Hirsutella rhossiliensis, an aureobasidin A-resistant ascomycete fungus.
Hirsutella rhossiliensis, a nematophagous fungus belonging to the Ascomycota, is resistant to aureobasidin A (AbA). In this fungus, the biosynthetic pathway leading to mannosylinositolphosphoceramides, which is inhibited by AbA, was not detected. Instead, this fungus contains neutral complex glycosphingolipids (GSLs) and monoglycosylceramides. Except for monoglycosylceramides, neutral GSLs share a neogala-series core structure, Galbeta1-6Galbeta1-Cer. Among the GSLs of H. rhossiliensis, three novel GSLs with terminal Man and Glc residues on the sugar chain were elucidated. We analyzed GSL structure using compositional sugar, fatty acid, and sphingoid analyses, methylation analysis, matrix-assisted laser desorption ionization time-of-flight/mass spectrometry (MALDI-TOF MS), and (1)H nuclear magnetic resonance spectroscopy (NMR). The following structures were determined: Manalpha1-3Galbeta1-6Galbeta1-6Galbeta1-Cer; Glcalpha1-2Galbeta1-6Galbeta1-6Galbeta1-Cer; and Manalpha1-3Galbeta1-6(Glcalpha1-4)Galbeta1-6Galbeta1-Cer. In the ceramides, the fatty acids were predominantly saturated h24:0-acids and the sphingoids were predominately t18:0- or t18:1-sphingoids. In contrast, the ceramides of Glcbeta1-Cer contained d18:2- and d19:2-sphingoids. These findings indicate the presence of a novel biosynthetic pathway of neogala-series GSLs in fungi.


Transvaginal ultrasonography compared with Bishop score for predicting cesarean section after induction of labor.
Reproductive health researchers are interested in finding better methods for predicting an unwanted type of delivery after induction of labor. The aim of this study was to compare the value of transvaginal ultrasonography findings and the Bishop score in predicting cesarean section after induction of labor. Two hundred women with singleton pregnancies undergoing induction of labor at 37-42 weeks were enrolled in this prospective study. Transvaginal investigation was done for all participants prior to induction. To compare the predictive value of the methods, receiver-operating characteristic (ROC) curves were plotted and equality of the area under curve (AUC) was tested. The mean age of the participants was 29.9 years, mean gestational age was 39.6 weeks, and mean gravid was 1.5. The AUC calculated for Bishop score was 0.39 (95% confidence interval [CI] 0.3-0.48). The AUC for cervical length measured by ultrasonography was 0.69 (95% CI 0.6-0.77). The AUC for the posterior cervical angle measured by ultrasonography was 0.38 (95% CI 0.29-0.47). Testing equality of the ROC curves for these three methods showed the ROC for cervical length to be statistically different from both Bishop score and posterior cervical angle (P < 0.001). However, the difference in ROC area compared between Bishop score and posterior cervical angle was not statistically significant. Based on our findings and available information in the literature, it seems that cervical length measured by transvaginal ultrasonography has the potential to replace the traditional Bishop score, provided that such a facility is available when needed.


Flow modulation algorithms for intra-aortic rotary blood pumps to minimize coronary steal.
Intra-aortic rotary blood pumps (IARBPs) have been used for partial cardiac support during cardiogenic shock, myocardial infarction, percutaneous coronary intervention, and potentially viable for long-term circulatory support. Intra-aortic rotary blood pump support continuously removes volume from the aortic root, which lowers left ventricular preload, external work (LVEW), and improves end-organ perfusion. However, IARBP support diminishes aortic root pressure and coronary artery. It may also create "coronary steal," which may produce a myocardial hypoxic state adversely affecting patient outcomes. Our objective was to develop IARBP flow modulation algorithms to eliminate coronary steal and improve the myocardial supply-demand ratio without compromising the clinical benefits of restored end-organ perfusion and reduced LVEW. The hemodynamic responses of the native ventricle, coronary, and systemic vasculature to timing and synchronization of IARBP flow modulation (cyclic variation of pump flow) were investigated using a clinical heart failure (HF) computer simulation model. A total of more than 150 combinations of varying pulse widths and time-shifts to modulate IARBP flow were tested at mean IARBP flow rates of 2, 3, and 4 L/min, and compared with HF baseline values (no IARBP support). Increasing IARBP support augmented cardiac output and diminished LVEW. Nonmodulated IARBP support significantly diminished mean diastolic coronary flow (-49%) and myocardial supply-demand ratio (-12%) compared with HF baseline. Intra-aortic rotary blood pump flow modulation increased mean diastolic coronary flow (+17%) and myocardial supply-demand ratio (+24%) compared with nonmodulated IARBP (constant flow). Modulation and synchronization of IARBP support augmented coronary artery perfusion and myocardial supply-demand ratio in simulated clinical HF while also restoring end-organ perfusion and reducing LVEW. Implementation of IARBP support with flow modulation may prevent myocardial hypoxia and improve patient outcomes. However, even with flow modulation, IARBP support provides a smaller improvement in myocardial supply demand ratio compared to ventricular assist devices and intra-aortic balloon pumps.


Hot carrier dynamics in MoS2/WS2heterostructure.
TMDs based heterostructure have drawn much attention for its potential application in photoelectric devices benefiting from the rapid and effective carrier separation and ultra-long interlayer exciton lifetime. Recent studies on carrier dynamics of TMDs based heterostructures are mainly focused on the transfer process of photo-generated carriers across the interface and lifetime of interlayer exciton but little attention is paid on the dynamics of hot carriers. Here, the carrier dynamics of hot carriers in MoS2/WS2heterostructure is investigated by transient absorption spectra. Rapid separation of electron and hole is observed. More importantly, hot carriers of C exciton, which contribute to the absorption of most of the visible light, could compensate for the carrier loss in the band edge exciton energy band through the intervalley transfer process. This re-injection process of hot carriers of C exciton could compensate for carrier depletion in photoelectric devices, thus may greatly improve the light utilization in optoelectronic devices.


Peptidoglycan deacetylation in Helicobacter pylori contributes to bacterial survival by mitigating host immune responses.
An oxidative stress-induced enzyme, peptidoglycan deacetylase (PgdA), in the human gastric pathogen Helicobacter pylori was previously identified and characterized. In this study, we constructed H. pylori pgdA mutants in two mouse-adapted strains, X47 and B128, to investigate the role of PgdA in vivo (to determine the mutants' abilities to colonize mice and to induce an immune response). H. pylori pgdA mutant cells showed increased sensitivity to lysozyme compared to the sensitivities of the parent strains. We demonstrated that the expression of PgdA was significantly induced (3.5-fold) when H. pylori cells were in contact with macrophages, similar to the effect observed with oxidative stress as the environmental inducer. Using a mouse infection model, we first examined the mouse colonization ability of an H. pylori pgdA mutant in X47, a strain deficient in the major pathway (cag pathogenicity island [PAI] encoded) for delivery of peptidoglycan into host cells. No animal colonization difference between the wild type and the mutant was observed 3 weeks after inoculation. However, the pgdA mutant showed a significantly attenuated ability to colonize mouse stomachs (9-fold-lower bacterial load) at 9 weeks postinoculation. With the cag PAI-positive strain B128, a significant colonization difference between the wild type and the pgdA mutant was observed at 3 weeks postinoculation (1.32 × 10(4) versus 1.85 × 10(3) CFU/gram of stomach). To monitor the immune responses elicited by H. pylori in the mouse infection model, we determined the concentrations of cytokines present in mouse sera. In the mice infected with the pgdA mutant strain, we observed a highly significant increase in the level of MIP-2. In addition, significant increases in interleukin-10 and tumor necrosis factor alpha in the pgdA mutant-infected mice compared to the levels in the wild-type H. pylori-infected mice were also observed. These results indicated that H. pylori peptidoglycan deacetylation is an important mechanism for mitigating host immune detection; this likely contributes to pathogen persistence.


Analysis of the role of the bel and bet open reading frames of human foamy virus by using a new quantitative assay.
We have constructed a BHK-21-derived indicator cell line containing a single integrated copy of the beta-galactosidase (beta-Gal) gene under control of the human foamy virus (HFV) long terminal repeat promoter (from -533 to +20). These foamy virus-activated beta-Gal expression (FAB) cells can be used in a quantitative assay to measure the infectious titer of HFV. Our results show that the FAB assay is 50 times more sensitive than determination of the virus titer by the end-point dilution method. Using the FAB assay, we have found that HFV can productively replicate in several erythroblastoid cell lines as well as in the Jurkat T-cell line. We have also examined the roles of bel2, bet, and bel3 in viral replication by constructing proviral HFV clones in which the reading frame of Bel2, Bet, or Bel3 is disrupted by placement of translation stop codons. Analysis of these mutants reveals that while the bel3 gene is not required for viral replication in vitro, mutations in the bel2 or bet gene decrease cell-free viral transmission approximately 10-fold.


Targeted disruption of a human interferon-inducible gene detected by secretion of human growth hormone.
A new method is described for the sib-selection of 'targeted' mammalian cells that have undergone homologous recombination (HR) with a transfected DNA construct. This method has been used to disrupt the 6-16 gene, an interferon (IFN)-inducible gene of unknown function, in two different human cell lines. Disruption was caused by integration of a targeting construct containing a promoterless gene for human growth hormone (hGH) which was expressed after HR with the 6-16 gene. Homologous recombinants were detected in pools of non-homologous recombinants by the appearance of hGH in the growth medium after the addition of IFN. Secondary and tertiary rounds of hGH assays were used to sib-select 9 homologous recombinants that were shown to have 1, 2 or 3 copies of the targeting construct integrated at the 6-16 locus. The method, which should be applicable to other transcribed targets, provides an alternative to selection methods, and offers advantages over other screening methods in being simple, rapid, sensitive and reliable.


Decoupling of conductivity relaxation from structural relaxation in protic ionic liquids and general properties.
The main focus of this work is the study of conductivity relaxation of amorphous lidocaine hemisuccinate near the glass transition at ambient pressure. Measurements have been made using broadband dielectric spectroscopy (BDS) and temperature-modulated differential scanning calorimetry. Our study shows that the ion conductivity relaxation becomes increasingly faster than the structural relaxation as the glass transition temperature Tg is approached. At Tg the structural relaxation time is longer than the conductivity relaxation times by three decades, i.e. the decoupling index Rτ is about 3. Decoupling is accompanied by the ion conductivity relaxation which narrows in its frequency dispersion with decreasing temperature. This abnormal behavior is identical to that found in two other protic ionic liquids (PILs), procaine HCl and procainamide HCl. Considering that the phenomenon has been found before in several inorganic ionic glass-formers and now in three protic ionic liquids, it could be a general property of ionically conducting glass-forming substances, although more cases have to be studied before a definitive conclusion can be made. We show that it can be rationalized within the framework of the Coupling Model.


Enzymatic assessment of cholesterol on electrophoresis gels for estimating HDL size distribution and plasma concentrations of HDL subclasses.
The aim of this study was to develop an enzymatic cholesterol staining method to determine HDL subclasses in a polyacrylamide gradient gel electrophoresis, which further allows staining by protein in the same electrophoresis lane. HDLs from 120 healthy individuals were separated through nondenaturing PAGE. HDLs were stained for cholesterol using an enzymatic semisolid mixture. Once the gels were unstained, they were stained again for proteins with Coomassie blue. The proportions of HDL subclasses were determined by densitometry. HDL subclasses were transformed to concentrations using as reference HDL-cholesterol plasma levels. This method is comparable in linearity and reproducibility to Coomassie blue staining, although it provides quantitative data. As expected, HDL size distribution shifted toward larger particles when determined by cholesterol as compared with protein. With this method, we observed different proportions of HDL subclasses between men and women as compared with Coomassie blue staining. We described a method to determine HDL size distribution by enzymatic cholesterol staining on polyacrylamide gels. The method allows the quantification of the cholesterol plasma concentration of each HDL subclass with the possibility to further stain the protein in the same sample. The combination of HDL staining by cholesterol and protein on electrophoresis gels provides information that may have clinical relevance.


Synthesis and characterization of new coordination polymers with tunable luminescent properties generated from bent 1,2,4-triazole-bridged N,N'-dioxides and Ln(III) salts.
A new bent 1,2,4-triazole-bridged N,N'-dioxide ligand, namely, 3,5-bis(3-pyridyl-N-oxide)-4-amino-1,2,4-triazole (L2), was designed and synthesized by the oxidation of 3,5-bis(3-pyridyl)-4-amino-1,2,4-triazole with H(2)O(2) in the presence of HOAc at ambient temperatures. Eleven Ln(III)-based coordination polymers have been successfully prepared by the solution reactions of L2 with various Ln(III)-perchlorates. The structures of these new Ln(III) polymers clearly reflect the effect of the lanthanide contraction. Compounds 1-6 feature a two-dimensional net, in which the Ln(III) atoms adopt a nine-coordinate {LnO(9)} sphere due to their larger ionic radii, whereas the Ln(III) centers in the one-dimensional double-stranded chains of 7-11 with smaller ionic radii lie in a {LnO(8)} coordination environment. In addition, the tunable emission intensity was realized on 7 by controlling the type of the involved counterion on the basis of a reversible solid-state anion exchange. Such reversible solid-state anion exchange might provide an alternative approach to tuning the luminescence.


Regulation of cellular RNA nano-particle assembly by splicing factor SRp20.
Cellular RNA nano-particles (RNA granules) such as stress granule (SG) and P-body (PB) are translationally silenced mRNA-protein complexes. Previously, a genome-wide loss-of-function screen using oligomeric siRNAs targeting potential drug target genes was performed to identify genes that are involved in SG and PB assembly. SRp20 (SRSF3), a splicing regulator, was identified as a potential regulator for the RNA granule assembly. Here, we show that SRp20 is a bona-fide RNA granule component using antibody against SRp20 as well as Flag-tagged SRp20 through immunofluorescence microscopy. More importantly, upon knockdown of SRp20 using siRNA, RNA granule formation was potently disrupted indicating that SRp20 is one of the major structural components of SGs and PBs. Interestingly, polysome profiling analyses displayed that SRp20 is distributed in all ribosomal fractions suggesting a potential role of SRp20 as a post-transcriptional mRNA regulator. These results broaden the functional role of SRp20 from the nuclear RNA processing events to the cytoplasmic post-transcriptional mRNA regulatory events through RNA granules that are critical for the regulation of gene expression.


Cascades in action: How the transition to walking shapes caregiver communication during everyday interactions.
New motor skills supply infants with new possibilities for action and have consequences for development in unexpected places. For example, the transition from crawling to walking is accompanied by gains in other abilities-better ways to move, see the world, and engage in social interactions (e.g., Adolph & Tamis-LeMonda, 2014). Do the developmental changes associated with walking extend to the communicative behaviors of caregivers? Thirty infants (14 boys, 16 girls; 93% White, not Hispanic or Latino) and their caregivers (84% held a college degree or higher) were observed during everyday activities at home during the two-month window surrounding the onset of walking (M infant age = 11.98 months, range = 8.74-14.86). Using a cross-domain coding system, we tracked change in the rates of co-occurrence between infants' locomotor actions and caregivers' concurrent language and gesture input. We examined these relations on two timescales-across developmental time, as infants transitioned from crawling to walking, and in real time based on moment-to-moment differences in infant posture. A consistent pattern of results emerged: compared to crawling, bouts of infant walking were more likely to co-occur with caregiver language and gestures that either requested or described movement or provided information about objects. An effect of infants' real-time behavior was also discovered, such that infants were more likely to hear language from their caregivers when they moved while upright compared to prone. Taken together, findings suggest that the emergence of walking reorganizes the infant-caregiver dyad and sets in motion a developmental cascade that shapes the communication caregivers provide. (PsycInfo Database Record (c) 2022 APA, all rights reserved).