Concurrent Validity Between Live and Home Video Observations Using the Alberta Infant Motor Scale.
Serial assessment of gross motor development of infants at risk is an established procedure in neonatal follow-up clinics. Assessments based on home video recordings could be a relevant addition. In 48 infants (1.5-19 months), the concurrent validity of 2 applications was examined using the Alberta Infant Motor Scale: (1) a home video made by parents and (2) simultaneous observation on-site by a pediatric physical therapist. Parents' experiences were explored using a questionnaire. The intraclass correlation coefficient agreement between live and home video assessment was 0.99, with a standard error of measurement of 1.41 items. Intra- and interrater reliability: intraclass correlation coefficients were more than 0.99. According to 94% of the parents, recording their infant's movement repertoire was easy to perform. Assessing the Alberta Infant Motor Scale based on home video recordings is comparable to assessment by live observation. The video method is a promising application that can be used with low burden for parents and infants.


A systematic review of the psychometric properties of self-reported scales assessing burn contractures reveals the need for a new tool to measure contracture outcomes.
Approximately 40% of burn patients develop scar contractures. It is unknown which scar contracture therapy best optimizes activities of daily living (ADL).The appropriateness of self-reported outcome tools in measuring anti-scar contracture therapies has not been assessed. We conducted a systematic review to determine the quality of existing self-reported scales in measuring ADL among burn patients by analyzing and comparing psychometric properties-factor analysis, validity, reliability, and responsiveness. EMBASE, LILACS, American Psychological Association PsycNET databases were searched for relevant articles. Forty-one articles discussing 10 burn and non-burn-specific scales met eligibility criteria of ADL assessment, and available psychometric analyses. A common strength in most scales was good overall reliability. Common weaknesses were insufficient data on factor analyses, content validity specific to ADL assessment, and responsiveness. The psychometric analyses studies on these scales had poor sample variability. There is insufficient data on the dimensionality and responsiveness of existing scales to support their use for measuring ADL in burn patients. Existing scales do not comprehensively measure ADLs as an isolated parameter. A psychometrically valid, comprehensive self-reported burn contracture scale that measures ADLs among a diverse group of burn patients needs to be developed to optimize burn contracture treatments and develop new therapies.


[Do mobile telephones have adverse effects on the functions of implantable cardioverter defibrillators?].
The aim of this study was to investigate the effects of widely used mobile telephones on the functions of implantable cardioverter-defibrillators (ICD). The study included 9 patients (2 women, 7 men, mean age 65.5 +/- 6) with coronary artery disease who had underwent transvenous ICD implantation due to sustained ventricular tachycardia and/or fibrillation. First the test was performed on the basal conditions of ICD. Then, spontaneous heart rate of the patient was programmed to 10 beats/minute on VVI mode and the test was repeated. Two mobile telephones were located symmetrically 50 cm, 30 cm, 20 cm and 10 cm away from the ICD pocket in the pectoralis muscle and finally the mobile telephones antennas were touched to the pockets. On these different distances, the test was repeated during opening, standby, calling, talking and closing of the telephones. Possible ICD dysfunctions such as improper antitachycardic shock, inhibition of pacemaker functions, conversion to ventricular asynchronous mode (VOO) and development of ventricular trigger in devices with two chamber pacemaker functions were tested. The changes were observed on intracardiac and surface ECG's. There were no changes in the basal and pacemaker functions of ICD's and no symptoms in any patients. We have concluded that mobile telephones have no adverse effects on the functions of types of ICD assessed in the study.


Regulation of the synthesis of the major surfactant apoprotein in fetal rabbit lung tissue.
Antibodies directed against the major apoprotein of rabbit lung surfactant, a 29-36-kDa glycoprotein, were used to study changes in the levels of translatable surfactant apoprotein mRNA in rabbit lung tissue during development, as well as the effects of cortisol and cyclic AMP analogues on the levels of surfactant apoprotein and its mRNA in fetal rabbit lung tissue in organ culture. The major surfactant apoprotein and its mRNA were undetectable in lung tissues of 21-day gestational age fetal rabbits. Translatable mRNA specific for the major surfactant apoprotein was first detectable in lung tissues of 26-day fetuses, increased 25-fold on day 28, reached peak levels at day 31, and declined after birth. Incubation of 21-day fetal rabbit lung explants with cortisol in serum-free medium resulted in an increase in the specific content of the 29-36-kDa apoprotein. Cyclic AMP analogues and forskolin, an activator of adenylate cyclase, also caused a marked increase in the accumulation of surfactant apoprotein. When fetal lung explants were incubated with cortisol and dibutyryl cyclic AMP in combination, the specific content of the surfactant apoprotein was increased to levels greater than that of explants treated with either cortisol or dibutyryl cyclic AMP alone. These effects of dibutyryl cyclic AMP and cortisol on surfactant apoprotein accumulation were associated with comparable changes in the levels of translatable surfactant apoprotein mRNA. Thus, we have shown for the first time that the induction of pulmonary surfactant apoprotein synthesis during differentiation in vitro and in vivo is associated with an increase in the level of translatable mRNA and that cortisol and cyclic AMP increase both the accumulation of the major surfactant apoprotein and the corresponding mRNA in fetal rabbit lung tissue in vitro.


Gene Therapy Rescues Retinal Degeneration in Receptor Expression-Enhancing Protein 6 Mutant Mice.
Hereditary retinal dystrophy is clinically defined as a broad group of chronic and progressive disorders that affect visual function by causing photoreceptor degeneration. Previously, we identified mutations in the gene encoding receptor expression-enhancing protein 6 (REEP6), in individuals with autosomal recessive retinitis pigmentosa (RP), the most common form of inherited retinal dystrophy. One individual was molecularly diagnosed with biallelic REEP6 mutations, a missense mutation over a frameshift mutation. In this study, we generated Reep6 compound heterozygous mice, Reep6L135P/-, which mimic the patient genotype and recapitulate the early-onset retinal degeneration phenotypes observed in the individual with RP. To determine the feasibility of rescuing the Reep6 mutant phenotype via gene replacement therapy, we delivered Reep6.1, the mouse retina-specific isoform of REEP6, to photoreceptors of Reep6 mutant mice on postnatal day 20. Evaluation of the therapeutic effects 2 months posttreatment showed improvements in the photoresponse as well as preservation of photoreceptor cells. Importantly, guanylyl cyclase 1 (GC1) expression was also restored to the outer segment after treatment. Furthermore, rAAV8-Reep6.1 single treatment in Reep6 mutant mice 1 year postinjection showed significant improvements in retinal function and morphology, suggesting that the treatment is effective even after a prolonged period. Findings from this study show that gene replacement therapy in the retina with rAAV overexpressing Reep6 is effective, preserving photoreceptor function in Reep6 mutant mice. These findings provide evidence that rAAV8-based gene therapy can prolong survival of photoreceptors in vivo and can be potentially used as a therapeutic modality for treatment of patients with RP.


Ethnic Variance in Prevalence of COPD among Smokers in a Real World Setting.
Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent and progressive airflow limitation generally caused by prolonged cigarette smoking. Ethnic differences have been reported regarding COPD risk from smoking. The purpose of this study was to compare COPD prevalence in Hispanic and Caucasian smokers in a real-world setting. We studied consecutive patients referred to the community-based pulmonary practice. Hispanic and Caucasian smokers were included in the study. The clinical diagnosis of COPD was recorded from the chart. COPD was defined by PFT using GOLD criteria. Exclusion criteria were other ethnicities, non-smokers, and patients with a history of asthma /other pulmonary conditions. We reviewed a total of 1,313 consecutive PFTs of which 797 patients met our inclusion criteria. The prevalence of COPD among Hispanics was found to be lower by both clinical diagnosis as well as by spirometry compared to Caucasians (41.6% vs 54.2%). In Hispanics, clinical diagnosis was 91% higher by PFT, whereas for Caucasians, it was 6% lower. The odds of developing COPD (diagnosed based on FEV1/FVC ratio <70%) in the Caucasians are 4.1 times higher than Hispanics (Odds Ratio: 4.1; 95%CI: 2.8-5.9). Hispanic smokers have a lower prevalence of COPD both by the clinical diagnosis as well as by PFT. There is a significant disconnection between clinical and PFT diagnosis of COPD in Hispanic patients. The genetic basis of lower COPD risk and prevalence in Hispanics needs to be better understood. Spirometry threshold criteria for confirming a diagnosis of COPD may need to be modified based on ethnicity in clinical practice.


Lexical variation and change in british sign language.
This paper presents results from a corpus-based study investigating lexical variation in BSL. An earlier study investigating variation in BSL numeral signs found that younger signers were using a decreasing variety of regionally distinct variants, suggesting that levelling may be taking place. Here, we report findings from a larger investigation looking at regional lexical variants for colours, countries, numbers and UK placenames elicited as part of the BSL Corpus Project. Age, school location and language background were significant predictors of lexical variation, with younger signers using a more levelled variety. This change appears to be happening faster in particular sub-groups of the deaf community (e.g., signers from hearing families). Also, we find that for the names of some UK cities, signers from outside the region use a different sign than those who live in the region.


Synergistic interaction of hyperthermia and Gemcitabine in lung cancer.
Hyperthermia increases cytotoxicity of various antineoplastic agents. We investigated the cytotoxic effects of Gemcitabine and/or hyperthermia on BZR-T33 (human non-small-cell lung cancer cells) in vitro and in immune-suppressed athymic nude mice. Isobologram analysis of monolayer cell cultures for cytotoxicity demonstrates a synergistic interaction between hyperthermia and Gemcitabine. Clonogenic results show significant reductions in surviving fractions and colony size for both therapies; greatest reduction was for the combined therapy group. Using cell cycle analysis, hyperthermia enhanced Gemcitabine-induced G2-M arrest resulting in destruction of 3.5 log cells. Apoptotic studies (Annexin-V FITC staining) showed that hyperthermia augmented Gemcitabine-induced apoptosis. Transmission electron microscopy demonstrated pathology observed in cultures exposed to either therapy present in cultures exposed to both therapies. Studies in nude mice show that the combination therapy group had both an initial decrease in tumor size, and a significantly delayed rate of growth. Additionally, using tumor material harvested from nude mice two days after end to treatment reveals a significantly greater apoptotic index and significantly smaller mitotic index for the combined therapy group. Western blots of the same tumor material, showed that heat shock protein 70 was not significantly increased, however, caspase-3 activity of was significantly increased because of the combined therapy. In conclusion, the combined therapy is synergistic in effect because of hyperthermia enhancing Gemcitabine-induced apoptosis.


Self-control and alcohol restraint: an initial application of the self-control strength model.
Individuals whose self-control strength is depleted through the prior exertion of self-control may consume more alcohol in situations that demand restraint. Male social drinkers either exerted self-control by suppressing their thoughts or did not exert self-control while doing arithmetic. They then sampled beer. Participants expected a driving test after drinking and therefore were motivated to limit their intake. Individuals who suppressed their thoughts consumed more and achieved a higher blood alcohol content than those who did arithmetic. The groups did not differ in mood, arousal, or frustration. Individuals higher in trait temptation to drink consumed more after suppressing their thoughts relative to those lower in trait temptation. Alcohol intake may be a function of temptation to drink and self-control strength.


Characterization of nucleoside transport systems in cultured rat epididymal epithelium.
The nucleoside transport systems in cultured epididymal epithelium were characterized and found to be similar between the proximal (caput and corpus) and distal (cauda) regions of the epididymis. Functional studies revealed that 70% of the total nucleoside uptake was Na(+) dependent, while 30% was Na(+) independent. The Na(+)-independent nucleoside transport was mediated by both the equilibrative nitrobenzylthioinosine (NBMPR)-sensitive system (40%) and the NBMPR-insensitive system (60%), which was supported by a biphasic dose response to NBMPR inhibition. The Na(+)-dependent [(3)H]uridine uptake was selectively inhibited 80% by purine nucleosides, indicating that the purine nucleoside-selective N1 system is predominant. Since Na(+)-dependent [(3)H]guanosine uptake was inhibited by thymidine by 20% and Na(+)-dependent [(3)H]thymidine uptake was broadly inhibited by purine and pyrimidine nucleosides, this suggested the presence of the broadly selective N3 system accounting for 20% of Na(+)-dependent nucleoside uptake. Results of RT-PCR confirmed the presence of mRNA for equilibrative nucleoside transporter (ENT) 1, ENT2, and concentrative nucleoside transporter (CNT) 2 and the absence of CNT1. It is suggested that the nucleoside transporters in epididymis may be important for sperm maturation by regulating the extracellular concentration of adenosine in epididymal plasma.


Probable L-forms of Nocardia asteroides induced in cultured mouse peritoneal macrophages.
Mouse peritoneal macrophages were infected with varying numbers of Nocardia asteroides 10905, and the fate of the ingested organisms was determined by viable plate count (VPC), light microscopy (LM), immunofluorescent microscopy (IM), and electron microscopy (EM). The results obtained with these methods differed. VPC indicated that intracellular Nocardia decreased in numbers during the first 12 days, followed by significant increases after 16 days. LM suggested that N. asteroides 10905 was slowly degraded by macrophages with no subsequent increases observed. In contrast, IM demonstrated large numbers of intracellular Nocardia throughout the experiment. EM studies of infected macrophages failed to demonstrate intact bacteria after 8 days; however, wall-less and spheroplast-like organisms were seen. These results suggested that N. asteroides 10905 was present within the macrophages in an altered form. By using hypertonic culture medium, we were able to isolate, from infected macrophages, organisms which exhibited many of the properties of bacterial L-forms. IM demonstrated these variants to be of nocardial origin. These altered forms also reverted to typical nocardial cells either spontaneously or upon transfer into broth. These findings indicate that N. asteroides 10905 is capable of existing within macrophages in an altered state. Further investigation is in progress to determine whether these altered forms represent L-forms or transitional-phase variants.


Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program.
We assessed the prognostic value of minimal residual disease (MRD) within the ML17638 phase 3 trial from the Fondazione Italiana Linfomi, investigating the role of rituximab maintenance in elderly follicular lymphoma (FL) patients after a brief first-line chemoimmunotherapy. MRD for the bcl-2/IgH translocation was determined on bone marrow cells in a centralized laboratory belonging to the Euro-MRD consortium, using qualitative and quantitative polymerase chain reactions (PCRs). Of 234 enrolled patients, 227 (97%) were screened at diagnosis. A molecular marker (MM) was found in 51%. Patients with an MM were monitored at 8 subsequent times. Of the 675 expected follow-up samples, 83% were analyzed. Conversion to PCR negativity predicted better progression-free survival (PFS) at all post-treatment times (eg, end of therapy: 3-year PFS, 72% vs 39%; P < .007). MRD was predictive in both maintenance (83% vs 60%; P < .007) and observation (71% vs 50%; P < .001) groups. PCR positivity at the end of induction was an independent adverse predictor (hazard ratio, 3.1; 95% confidence interval, 1.36-7.07). MRD is a powerful independent outcome predictor in FL patients who receive rituximab-intensive programs, suggesting a need to investigate its value for decision-making. This trial was registered at www.clinicaltrial.gov as #NCT01144364.


The Leipzig experience with robotic valve surgery.
The study describes the single-center experience using robot-assisted videoscopic mitral valve surgery and the early results with a remote telemanipulator-assisted approach for mitral valve repair. Out of a series of 230 patients who underwent minimally invasive mitral valve surgery, in 167 patients surgery was performed with the use of robotic assistance. A voice-controlled robotic arm was used for videoscopic guidance in 152 cases. Most recently, a computer-enhanced telemanipulator was used in 15 patients to perform the operation remotely. The mitral valve was repaired in 117 and replaced in all other patients. The voice-controlled robotic arm (AESOP 3000) facilitated videoscopic-assisted mitral valve surgery. The procedure was completed without the need for an additional assistant as "solo surgery." Additional procedures like radiofrequency ablation and tricuspid valve repair were performed in 21 and 4 patients, respectively. Duration of bypass and clamp time was comparable to conventional procedures (107 A 34 and 50 A 16 min, respectively). Hospital mortality was 1.2%. Using the da Vinci telemanipulation system, remote mitral valve repair was successfully performed in 13 of 15 patients. Robotic-assisted less invasive mitral valve surgery has evolved to a reliable technique with reproducible results for primary operations and for reoperations. Robotic assistance has enabled a solo surgery approach. The combination with radiofrequency ablation (Mini Maze) in patients with chronic atrial fibrillation has proven to be beneficial. The use of telemanipulation systems for remote mitral valve surgery is promising, but a number of problems have to be solved before the introduction of a closed chest mitral valve procedure.


Implantable cardioverter defibrillator therapy in young individuals: comparison of conventional and subcostal approaches-a single-centre experience.
The aim of our study is to compare two approaches of implantable cardiac defibrillator (ICD) implantation, conventional (supra/subpectoral) and subcostal in young adults in terms of procedural complications and adverse events encountered during follow-up. From January 2007 to December 2013, all patients under the age of 50 years who received an ICD in our centre were included in this study. Patient's hospital records were analysed for procedural complications and adverse events during follow-up until December 2014. Data from device on first interrogation after implantation and on follow-up were also noted. A total of 106 patients of which 40.6% had Brugada's syndrome (65.1% male, age 33.6 ± 10.97 years) were included in analysis; 71 (61%) had ICD placed in (sub/supra) pectoral and 35 (33%) in subcostal position. Only seven patients received an epicardial lead system. During the follow-up period of 2.1 ± 1.8 years, 84.90% of the patients had no adverse events. Most of the complications, procedural and during follow-up, occur in conventionally placed, pectoral ICD. Lead follow-up data in both groups, conventional and subcostal, showed no difference in right ventricular (RV) shock impedance and R wave sensing, P-value = 0.56 and 0.77, respectively. Lead survival was 95 and 97%, respectively, in conventional and subcostal groups over a mean follow-up of 2.1 ± 1.8 years. Log-rank test for lead survival was not significant in terms of site of implantation. To the best our knowledge, this is the first study demonstrating subcostal ICD placement in young adults and resulting in equivalent to better outcomes when compared with conventionally placed pectoral ICD. Subcostal ICD placement might be considered an alternative option in young adults as it results in better procedural outcomes and also comparable rate of adverse events during follow-up, but bigger studies with a larger number of patients are needed for a definitive conclusion.


A new learning environment: combining clinical research with quality improvement.
The emphasis provided by quality improvement strategies on performance measurement and evaluation often results in our understanding of processes of care and, perhaps, better outcomes. There are different references for process evaluation: external peers, regional profiles of performance or a trending of one's own performance patterns. This paper proposes a methodology that enables learning from the daily practice of medicine by comparing alternative care processes and outcomes. Since it is estimated that 15-20% of medical practices are based on rigorous scientific data establishing their effectiveness, we have much to learn. We propose to learn from our daily practice by combining clinical research methods with quality improvement tools. The products comprise modified clinical trial and case-control studies. In a modified clinical trial, we would use a practice guideline as a control group and modify the guideline to create an experimental group. This method would maintain the internal validity of efficacy research while maintaining the external validity of effectiveness research. In the case-control method, it is possible to quantitate risk for a given outcome and focus improvement effort on factors associated with that outcome. We believe physicians will accept this learning approach because it is a more valid learning method than traditional quality improvement and, unlike randomized clinical trials, learning will occur in the daily practice of medicine.


Proton-detected solid-state NMR spectroscopy of spin-1/2 nuclei with large chemical shift anisotropy.
Constant-time (CT) dipolar heteronuclear multiple quantum coherence (D-HMQC) has previously been demonstrated as a method for proton detection of high-resolution wideline NMR spectra of spin-1/2 nuclei with large chemical shift anisotropy (CSA). However, 1H transverse relaxation and t1-noise often reduce the sensitivity of D-HMQC experiments, preventing the theoretical gains in sensitivity provided by 1H detection from being realized. Here we demonstrate a series of improved pulse sequences for 1H detection of spin-1/2 nuclei under fast MAS, with 195Pt SSNMR experiments on cisplatin as an example. First, a t1-incrementation protocol for D-HMQC dubbed Arbitrary Indirect Dwell (AID) is demonstrated. AID allows the use of arbitrary, rotor asynchronous t1-increments, but removes the constant time period from CT D-HMQC, resulting in improved sensitivity by reducing transverse relaxation losses. Next, we show that short high-power adiabatic pulses (SHAPs), which efficiently invert broad MAS sideband manifolds, can be effectively incorporated into 1H detected symmetry-based resonance echo double resonance (S-REDOR) and t1-noise eliminated (TONE) D-HMQC experiments. The S-REDOR experiments with SHAPs provide approximately double the dipolar dephasing, as compared to experiments with rectangular inversion pulses. We lastly show that sensitivity and resolution can be further enhanced with the use of swept excitation pulses as well as adiabatic magic angle turning (aMAT).


Decreased arteriolar tetrahydrobiopterin is linked to superoxide generation from nitric oxide synthase in mice fed high salt.
Impaired endothelium-dependent arteriolar dilation in mice fed high salt (HS) is due to local oxidation of nitric oxide (NO) by superoxide anion (O(2) (-)). We explored the possibility that "uncoupled" endothelial nitric oxide synthase (eNOS) is the source of this O(2) (-). Levels of L-arginine (L-Arg), tetrahydrobiopterin (BH(4)), and O(2) (-) (hydroethidine oxidation) were measured in spinotrapezius muscle arterioles of mice fed normal salt (0.45%, NS) or (4%, HS) diets for 4 weeks, with or without dietary L-Arg supplementation. The contribution of NO to endothelium-dependent dilation was determined from the effect of N(omega)-nitro-L-arginine methyl ester (L-NAME) on responses to acetylcholine (ACh). Arterioles in HS mice had lower [BH(4)] and higher O(2) (-) levels than those in NS mice. ACh further increased arteriolar O(2) (-) in HS mice only. L-Arg supplementation prevented the reduction in [BH(4)] in arterioles of HS mice, and O(2) (-) was not elevated in these vessels. Compared to NS mice, arteriolar ACh responses were diminished and insensitive to L-NAME in HS mice, but not in HS mice supplemented with L-Arg. These findings suggest that eNOS uncoupling due to low [BH(4)] is responsible for O(2) (-) generation and reduced NO-dependent dilation in arterioles of mice fed a HS diet.


Asymmetric structural motions of the homomeric alpha7 nicotinic receptor ligand binding domain revealed by molecular dynamics simulation.
A homology model of the ligand binding domain of the alpha7 nicotinic receptor is constructed based on the acetylcholine-binding protein crystal structure. This structure is refined in a 10 ns molecular dynamics simulation. The modeled structure proves fairly resilient, with no significant changes at the secondary or tertiary structural levels. The hypothesis that the acetylcholine-binding protein template is in the activated or desensitized state, and the absence of a bound agonist in the simulation suggests that the structure may also be relaxing from this state to the activatable state. Candidate motions that take place involve not only the side chains of residues lining the binding sites, but also the subunit positions that determine the overall shape of the receptor. In particular, two nonadjacent subunits move outward, whereas their partners counterclockwise to them move inward, leading to a marginally wider interface between themselves and an overall asymmetric structure. This in turn affects the binding sites, producing two that are more open and characterized by distinct side-chain conformations of W54 and L118, although motions of the side chains of all residues in every binding site still contribute to a reduction in binding site size, especially the outward motion of W148, which hinders acetylcholine binding. The Cys loop at the membrane interface also displays some flexibility. Although the short simulation timescale is unlikely to sample adequately all the conformational states, the pattern of observed motions suggests how ligand binding may correlate with larger-scale subunit motions that would connect with the transmembrane region that controls the passage of ions. Furthermore, the shape of the asymmetry with binding sites of differing affinity for acetylcholine, characteristic of other nicotinic receptors, may be a natural property of the relaxed, activatable state of alpha7.


Arrestin-independent constitutive endocytosis of GPR125/ADGRA3.
The orphan receptor GPR125 (ADGRA3) belongs to subgroup III of the adhesion G protein-coupled receptor (aGPCR) family. aGPCRs, also known as class B2 GPCRs, share basic structural and functional properties with other GPCRs. Many of them couple to G proteins and activate G protein-dependent and -independent signaling pathways, but little is known about aGPCR internalization and β-arrestin recruitment. GPR125 was originally described as a spermatogonial stem cell marker and studied for its role in Wnt signaling and cell polarity. Here, using cell-based assays and confocal microscopy, we show that GPR125 is expressed on the cell surface and undergoes constitutive endocytosis in a β-arrestin-independent, but clathrin-dependent manner, as indicated by colocalization with transferrin receptor 1, an early endosome marker. These data support that the constitutive internalization of GPR125 contributes to its biological functions by controlling receptor surface expression and accessibility for ligands. Our study sheds light on a new property of aGPCRs, namely internalization; a property described to be important for signal propagation, signal termination, and desensitization of class A (rhodopsin-like) and B1 (VIP/secretin) GPCRs.


Mesenteric blood flow response to dopamine infusion during myocardial infarction in the awake dog.
This study was designed to determine the effects of dopamine on the superior mesenteric arterial circulation of conscious dogs subjected to experimental myocardial infarction. Electromagnetic blood flow transducers were implanted on the superior mesenteric artery in 10 dogs. Direct infusion into the superior mesenteric artery of dopamine (2.5 micrograms/kg/min) after induction of acute myocardial infarction (AMI) revealed a steadily decreasing ability of dopamine to produce mesenteric vasodilation; 4 hr after AMI, infusion of dopamine decreased mesenteric resistance only 14 +/- 0.05%, which was significantly less (P less than 0.001) than during the control period when it decreased resistance 41 +/- 1.0%. Isoproterenol (N = 3) produced substantial increases in flow, despite the reduction in effectiveness of dopamine. Treatment of the 10 dogs with phenoxybenzamine, 5 mg directly into the superior mesenteric artery, restored the ability of dopamine to dilate the mesenteric bed. Beta-adrenergic blockage did not affect the dopaminergic vasodilation after alpha-blockade. The results of this study question the efficacy of dopamine to produce mesenteric vasodilation in the face of increased resistance in the splanchnic circulation during the acute myocardial infarction complicated by hypotension.


Assessment of riverine load of contaminants to European seas under policy implementation scenarios: an example with 3 pilot substances.
An evaluation of conventional emission scenarios is carried out targeting a possible impact of European Union (EU) policies on riverine loads to the European seas for 3 pilot pollutants: lindane, trifluralin, and perfluorooctane sulfonate (PFOS). The policy scenarios are investigated to the time horizon of year 2020 starting from chemical-specific reference conditions and considering different types of regulatory measures including business as usual (BAU), current trend (CT), partial implementation (PI), or complete ban (PI ban) of emissions. The scenario analyses show that the model-estimated lindane load of 745 t to European seas in 1995, based on the official emission data, would be reduced by 98.3% to approximately 12.5 t in 2005 (BAU scenario), 10 years after the start of the EU regulation of this chemical. The CT and PI ban scenarios indicate a reduction of sea loads of lindane in 2020 by 74% and 95%, respectively, when compared to the BAU estimate. For trifluralin, an annual load of approximately 61.7 t is estimated for the baseline year 2003 (BAU scenario), although the applied conservative assumptions related to pesticide use data availability in Europe. Under the PI (ban) scenario, assuming only small residual emissions of trifluralin, we estimate a sea loading of approximately 0.07 t/y. For PFOS, the total sea load from all European countries is estimated at approximately 5.8 t/y referred to 2007 (BAU scenario). Reducing the total load of PFOS below 1 t/y requires emissions to be reduced by 84%. The analysis of conventional scenarios or scenario typologies for emissions of contaminants using simple spatially explicit GIS-based models is suggested as a viable, affordable exercise that may support the assessment of implementation of policies and the identification or negotiation of emission reduction targets.


[Statistical characteristics of inhomogeneities of protein and chromation networks].
Natural textures (networks) are observed in many cases: the inter-cellular contact sites, endoplasmic reticulum membranes etc. The vast amount of experimental data was analyzed to produce the distribution histograms for the length of the segments in the protein and chromatin networks of different origin. The networks both from the eukaryotic cells and nucleis, as well as from E. coli and viruses are presented. Statistical analysis demonstrated that all experimentally observed histograms fit to the following formula: F(x) = (5(5)[4]) x x(4)x exp(-5x) where x =l/<l>, l- length of the network segment, and </> is the average length of the segment. In contrast to the Gaussian distribution, the distribution of the segments' lengths is markedly assymetrical. The shape of the distribution does not dependent on the origin of the analyzed network.


Alcohol and liver injury: dose-related or permissive effect?
The studies addressing the risk of development of cirrhosis of the liver in relation to alcohol consumption have been based on comparisons at the aggregate population level and at the individual level, on case-control studies and cohort studies, and on retrospective and prospective assessment of alcohol consumption. The ideal, but unfeasible, study design for estimation of the risk function is a prospective monitoring of alcohol consumption and recording of rate of development of cirrhosis per unit of time. Two recent studies, approaching this design, suggested that above a rather low, but not precisely determined, level of alcohol consumption, the risk of development of cirrhosis is not further influenced by the amount of alcohol consumed. A critical analysis of previous studies suggests that this risk function actually is compatible with their findings. The contention that alcohol abuse has a permissive rather than a dose-dependent role in the development of alcoholic liver injury encourages research into the additional factors that must act before the liver injury occurs.


Maximal polar growth potential depends on the polarisome component AgSpa2 in the filamentous fungus Ashbya gossypii.
We used actin staining and videomicroscopy to analyze the development from a spore to a young mycelium in the filamentous ascomycete Ashbya gossypii. The development starts with an initial isotropic growth phase followed by the emergence of germ tubes. The initial tip growth speed of 6-10 microm/h increases during early stages of development. This increase is transiently interrupted in response to the establishment of lateral branches or septa. The hyphal tip growth speed finally reaches a maximum of up to 200 micro/h, and the tips of these mature hyphae have the ability to split into two equally fast-growing hyphae. A search for A. gossypii homologs of polarisome components of the yeast Saccharomyces cerevisiae revealed a remarkable size difference between Spa2p of both organisms, with AgSpa2p being double as long as ScSpa2p due to an extended internal domain. AgSpa2 colocalizes with sites of polarized actin. Using time-lapse videomicroscopy, we show that AgSpa2p-GFP polarization is established at sites of branch initiation and then permanently maintained at hyphal tips. Polarization at sites of septation is transient. During apical branching the existing AgSpa2p-GFP polarization is symmetrically divided. To investigate the function of AgSpa2p, we generated two AgSPA2 mutants, a partial deletion of the internal domain alone, and a complete deletion. The mutations had an impact on the maximal hyphal tip growth speed, on the hyphal diameter, and on the branching pattern. We suggest that AgSpa2p is required for the determination of the area of growth at the hyphal tip and that the extended internal domain plays an important role in this process.


The effect of ruby laser light on cellular proliferation of epidermal cells.
In ruby laser-assisted hair removal, microscopic damage is often seen in the basal epidermal cells, where melanosomes are concentrated. It is not known whether this treatment leads to cellular hyperproliferation. It was the aim of this study to investigate this. Ten white patients were treated with the Chromos 694-nm Depilation Ruby Laser, and biopsies taken before and after treatments to assess the presence of cell hyperproliferation, which normally accompanies epidermal damage, with immunohistochemical staining of keratin 16 and Ki67. No evidence of cell hyperproliferation was seen in all specimens examined after ruby laser irradiation. The authors conclude that despite the possible microscopic damages seen in the basal epidermis after laser hair removal, there is no evidence of cellular hyperproliferation. This is in contrast to ultraviolet-irradiated cell damage, in which increased basal cell turnover is seen.


Velopharyngeal morphology of patients with persistent velopharyngeal incompetence following repushback surgery for cleft palate.
To characterize the velopharyngeal morphology of patients with persistent velopharyngeal incompetence (VPI) following repushback surgery for cleft palate. Seven patients with moderate to severe VPI following repushback surgery for secondary correction of cleft palate, and 14 patients who had already obtained complete velopharyngeal closure function (VPF) were enrolled. Control data were obtained from the longitudinal files of 20 normal children in Kyushu University Dental Hospital. Skeletal landmarks and measurements were derived from tracing of lateral roentgenographic cephalograms. The measurements included velar length, pharyngeal depth, and pharyngeal height and the ratio of velar length to pharyngeal depth. Additionally, the configuration of the upper pharynx (pharyngeal triangle) involving the cranial base, cervical vertebrae, and the posterior maxilla and also the position of posterior pharyngeal wall (PPW) in the pharyngeal triangle were analyzed. The VPI group had a significantly shorter velar length and greater pharyngeal depth, resulting in a smaller length/depth ratio than the controls. The points of PPW and cervical vertebrae of the VPI group were located more posteriorly and inferiorly than those in the group with complete VPF after the primary operation and the controls. The positions of cranial base and maxilla were not significantly different. Additionally, the position of PPW in the pharyngeal triangle was located significantly posteriorly and superiorly in the VPI group, compared with the controls. The craniopharyngeal morphology of patients with persistent VPI was characterized by a short palate, wide-based and counterclockwise-rotated pharyngeal triangle, and posteriorly and superiorly positioned PPW. These might be contributory factors for the prediction of VPF before repushback surgery for cleft palate.


A fuzzy Petri net-based expert system and its application to damage assessment of bridges.
In this paper, a fuzzy Petri net approach to modeling fuzzy rule-based reasoning is proposed to bring together the possibilistic entailment and the fuzzy reasoning to handle uncertain and imprecise information. The three key components in our fuzzy rule-based reasoning-fuzzy propositions, truth-qualified fuzzy rules, and truth-qualified fuzzy facts-can be formulated as fuzzy places, uncertain transitions, and uncertain fuzzy tokens, respectively. Four types of uncertain transitions-inference, aggregation, duplication, and aggregation-duplication transitions-are introduced to fulfil the mechanism of fuzzy rule-based reasoning. A framework of integrated expert systems based on our fuzzy Petri net, called fuzzy Petri net-based expert system (FPNES), is implemented in Java. Major features of FPNES include knowledge representation through the use of hierarchical fuzzy Petri nets, a reasoning mechanism based on fuzzy Petri nets, and transformation of modularized fuzzy rule bases into hierarchical fuzzy Petri nets. An application to the damage assessment of the Da-Shi bridge in Taiwan is used as an illustrative example of FPNES.


Induction of beta-lactamase enzymes: clinical applications for the obstetric-gynecologic patient.
The emergence of bacteria resistant to antibiotics has resulted in intensive research for new and improved beta-lactam antibiotics. Many improvements in antimicrobial agents are based on a knowledge of the mechanism responsible for resistance. This has led to the development of new extended-spectrum antibiotic compounds. However, several features have been noted since the development of extended-spectrum antibiotics, such as the rapid development of bacterial resistance, the induction of beta-lactamase enzyme activity by these stable antibiotics, failure to detect induced enzyme activity and resistance in the laboratory, and beta-lactam antagonism. The resistance of bacteria to antimicrobial agents has obvious impact on the selection of appropriate therapy against infections caused by these pathogens. Gram-negative anaerobic bacteria, such as Bacteroides fragilis and Bacteroides bivius, are organisms frequently recovered from women whose initial therapy for pelvic infection failed. The transfer of antimicrobial resistance in bacteria indicates that these organisms have a system for the spread of such resistance. Therefore determination of antimicrobial susceptibilities and prompt eradication of isolates from infected patients are necessary to delay the emergence of resistant organisms.


Microtubule-associated protein 2 (MAP2) is present in astrocytes of the optic nerve but absent from astrocytes of the optic tract.
Using the peroxidase-antiperoxidase staining technique at the light- and electron-microscope levels and two monoclonal antibodies against microtubule-associated protein 2 (MAP2), we found that astrocytes located at the periphery of the rat optic nerve were strongly stained, while those in the central region were very weakly stained. MAP2 immunoreactivity was present in astrocytes of the optic chiasm, but was absent from astrocytes in the optic tract. Inside astrocytes, MAP2 immunoreactivity was excluded from bundles of glial filaments. Treatment of animals with beta,beta'-iminodipropionitrile (IDPN), which caused axonal atrophy, enhanced the staining intensity of all optic nerve astrocytes. Axons and oligodendrocytes remained unstained. Using PAGE and Western immunoblots, we found that extracts from bovine optic nerve contained MAP2. Astrocytes in any other region of the nervous system were negative for MAP2 immunoreactivity, except of the pituicytes and the astrocytes of the fimbria of hippocampus. The optic nerve, neurohypophysis, and hippocampal fimbria are white matter tracts that travel unsupported and free of surrounding nervous tissue. These findings suggest that MAP2 is expressed in astrocytes that are under excessive mechanical stress and further indicate that MAP2 may function as a cytoskeletal rigidifying agent in certain cells.


Cancer trends in Taiwan.
Cancer is becoming a more important health problem in Taiwan with aging of populations and changes in lifestyles. This indicates that a population-based cancer registration database is essential to providing informative data on cancer prevention and policy setting. The Taiwan Cancer Registry was launched in 1979 and all reporting hospitals were mandated to submit cancer data to the central cancer registry following the enactment of the Cancer Control Act in 2003. The National Health Insurance program in Taiwan has successfully provided quality health care, comprehensive benefits and convenient access to treatment. Most cancers had a rapidly increasing incidence after the initiation of the NHI program. However, cancer incidence rates of nasopharynx of both genders slightly decreased throughout the entire period and incidence of stomach cancer of both genders and cervical cancer of females declined beginning in 1995. For childhood cancers, the major types of leukemia, lymphomas, central nervous system neoplasms and other epithelial neoplasms for males and females accounted for nearly 55% of all types. This study presents for the first time the secular changes and age patterns in the incidence of childhood cancer using national cancer data.


Fossil Canis from the tar pits of La Brea, Peru.
New fossil material has been obtained from La Brea, Peru. Included in this material are remains of a large wolflike canid which could not be referred to any living or fossil South American canine genus. Comparison with fossil canids from Rancho La Brea, Calif., shows that it closely resembles Canis (Aenocyon) dirus Leidy.


Human immunodeficiency-virus-related pulmonary infections in children.
Increasing numbers of children with human immunodeficiency virus (HIV) infection continue to be seen in the United States. Pulmonary infections constitute a major cause of morbidity and mortality in these children Pneumoncystis carinii pneumonia, pulmonary lymphoid hyperplasia/lymphoid interstitial pneumonitis, and bacterial pneumonias, all described in high frequency in the earliest cases of pediatric acquired immunodeficiency syndrome, remain the pulmonary diseases confronted most often. Other pathogens, such as Mycobacterium tuberculosis and respiratory virus infections are now being identified in increasing numbers in HIV-infected children. Advances in our understanding of these disease processes and their clinical manifestations have allowed development of a systematic approaches to the common problem of the HIV-infected child with fever, tachypnea, and hypoxemia and an abnormal chest radiograph. These approaches, coupled with improvements in available treatment options, have led to earlier diagnosis and improved survival. Prophylaxis strategies have been developed for the most serious pulmonary infections, especially P carinii pneumonia. However, lack of identification of infants and children at risk of HIV infection has limited their effectiveness. Pulmonary infections in HIV-infected children continue to take a high toll with regard to morbidity and mortality. Only with continued advances in primary therapy to slow progression of the underlying immunodeficiency and widespread use of available prophylactic guidelines will these be reduced.


Fibronectin-calcium phosphate composite layer on hydroxyapatite to enhance adhesion, cell spread and osteogenic differentiation of human mesenchymal stem cells in vitro.
Fibronectin (Fn) and type I collagen (Col) were immobilized on a surface of a hydroxyapatite (HAP) ceramic by coprecipitation with calcium phosphate in a supersaturated calcium phosphate solution prepared by mixing clinically approved infusion fluids. These proteins and the calcium phosphate precipitate formed a composite surface layer. As a result, the proteins were immobilized firmly as not to be released completely for 3 d in a physiological salt solution. When human mesenchymal stem cells (hMSCs) were cultured on a HAP ceramic in a differentiation medium supplemented with dexamethasone, beta-glycerophosphate and ascorbic acid, hMSCs spread well within 1 h. The alkaline phosphatase (ALP) activity of hMSCs cultured on the Fn-calcium phosphate composite layer significantly increased compared with that of hMSCs cultured on the untreated HAP ceramic. On the other hand, Col did not increase the ALP activity of hMSCs and no synergy between Fn and Col was observed. Therefore, the Fn-calcium phosphate composite layer formed on the HAP is useful for the enhancement of the spreading and osteogenic differentiation of hMSCs in vitro.


Power estimation of tests in log-linear non-uniform association models for ordinal agreement.
Log-linear association models have been extensively used to investigate the pattern of agreement between ordinal ratings. In 2007, log-linear non-uniform association models were introduced to estimate, from a cross-classification of two independent raters using an ordinal scale, varying degrees of distinguishability between distant and adjacent categories of the scale. In this paper, a simple method based on simulations was proposed to estimate the power of non-uniform association models to detect heterogeneities across distinguishabilities between adjacent categories of an ordinal scale, illustrating some possible scale defects. Different scenarios of distinguishability patterns were investigated, as well as different scenarios of marginal heterogeneity within rater. For sample size of N = 50, the probabilities of detecting heterogeneities within the tables are lower than .80, whatever the number of categories. In additition, even for large samples, marginal heterogeneities within raters led to a decrease in power estimates. This paper provided some issues about how many objects had to be classified by two independent observers (or by the same observer at two different times) to be able to detect a given scale structure defect. Our results also highlighted the importance of marginal homogeneity within raters, to ensure optimal power when using non-uniform association models.


Formulation, Optimization, and Evaluation of Allopurinol-Loaded Bovine Serum Albumin Nanoparticles for Targeting Kidney in Management of Hyperuricemic Nephrolithiasis : Formulation, optimization, and evaluation of ABNPs for kidney targeting.
The aim of present research work was to design, fabricate, optimize, and evaluate allopurinol (ALLO)-loaded bovine serum albumin nanoparticles (ABNPs) for kidney targeting of the drug and exploring the potential of fabricated ABNPs for management of hyperuricemia-related nephrolithiasis. ABNP formulation was prepared by employing desolvation technique, and its optimization was conducted by 2-factor-3-level central composite design (CCD) in order to achieve minimum particle size (PSA) and polydispersity index (PDI), maximum entrapment efficiency (EE), and zeta potential (ZP). Further, the optimized formulation (ABNPsopt) was also assessed for in vitro drug release study, TEM, DSC, XRD analysis, FTIR spectroscopy, and in vivo animal study. The in vivo study revealed that after 2 h of ABNPsopt administration, a significant concentration of ALLO was present in kidney (21.26-fold) as compared with serum while in case of standard pure drug group; no drug was seen in mice kidney and serum post 2 h administration, which indicates successful targeting of ALLO by formulating its albumin nanoparticles. Also, uric acid and pH levels were measured in serum and urine samples of mice which showed significant (P < 0.01) efficacy of ABNPsopt formulation in management of hyperuricemia-related nephrolithiasis. Histological studies on kidney samples also confirmed these outcomes. Findings of present study indicate higher kidney uptake of allopurinol from formulated ABNPsopt, which could be due to the specificity of albumin polymer for cubilin and megalin receptors, and it also serves as effective strategy in management of hyperuricemic-related nephrolithiasis.


Silencing of CPNE1-TRAF2 Axis Restrains the Development of Pancreatic Cancer.
Copine 1 (CPNE1) acts as a promoter in the progression of many kinds of cancers with the exception of pancreatic cancer (PC). This research is designed to probe the function of the CPNE1-tumor necrosis factor receptor-associated factor 2 (TRAF2) axis in PC. In vivo and in vitro models of PC were constructed, and a series of biological function tests, including MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], colony formation, flow cytometry, and immunohistochemistry, were performed. The level of CPNE1 elevated dramatically in PC cells. Downregulation of CPNE1in PC cells resulted in the inhibition of colony formation and proliferation. In addition, the silencing of CPNE1 induced the G1/S arrest and apoptosis in PC cells. Additionally, TRAF2 positively interacted with CPNE1 in PANC cells. CPNE1 silencing also inhibited the growth of tumors in in vivo mouse models. Functional experiments revealed that the anti-tumor effect of CPNE1 silencing was counteracted by TRAF2 overexpression, and the tumor-promoting effect of TRAF2 overexpression was reversed by CPNE1 silencing. In summary, our findings indicate that the silencing of the CPNE1-TRAF2 axis restrains PC development.


Influence of wastewater composition on biological nutrient removal in UniFed SBR process.
The effects of influent C/N ratio and C/P ratio on biological nutrient removal performance were investigated in a lab-scale UniFed SBR apparatus treating real domestic wastewater. The results showed that TN removal efficiency increased as C/N ratio increased from 43.6% at 2.8 to 80.8% at 5.7. But when C/N ratio increased further, TN removal efficiency increased very slowly. This was because when C/N ratio was higher than 5.7, complete denitrification in the sludge blanket during feed/decant period had been achieved, TN removal efficiency during this period always kept the maximum value and only TN removal efficiency during aeration period rose as C/N ratio increased. PO(4) (3-) removal efficiency increased as C/N ratio increased from 27.3% at 2.8 to 88.1% at 5.7. When C/N ratio was 6.5 and above, PO(4) (3-) concentration couldn't be detected in the effluent. When influent C/N ratio and volumetric exchange ratio were fixed at 6 and 33% respectively, as C/P ratio was higher than 33, PO(4) (3-) concentration of effluent always remained below the detection level and phosphorus removal efficiency kept stable at 100%, but as the C/P ratio was lower than 33, phosphorus removal efficiency increased as C/P ratio increased linearly. C/P ratio hardly affected TN removal efficiency, which always kept at 82.2%-85.8% in this study.


Intracerebral Hodgkin's lymphoma in a patient with human immunodeficiency virus.
Central nervous system (CNS) involvement by Hodgkin Lymphoma (HL) is rarely reported. Retrospective and prospective cohort studies suggest an incidence of 0.2-0.5%, mostly in relapsed disease. In spite of a 3 to 18-fold increased risk of HL in patients with human immunodeficiency virus (HIV), only two cases have been reported so far. In this paper, we now report a third case of HIV patient with HL who progressed with isolated CNS infiltration after a standard chemotherapy induced clinical remission. In 1991, when the first case of intracerebral involvement in HIV+ HL was reported an increase of this type of cases would have been expected, but only one more case has been reported since then.


[Herpes simplex virus type 2 encephalitis in a healthy adult patient: an unusual case].
Neurological infection by herpes simplex virus type 2 (HSV-2) is the cause of significant morbidity and mortality; and should be diagnosed and treated as soon as possible. Typically, it is characterized by fever, headache and behavioral changes. Symptoms association, laboratory tests results and diagnostic imaging are essential for early diagnosis and treatment of this disease, in order to prevent its fatal progression. We present the case of a 45-year-old male patient diagnosed with HSV-2 encephalitis due to chronic steroid use. In previously healthy adult patients, neurological HSV-2 infection due to chronic steroid use is extremely rare; and the association has not been previously described.


Calcitriol upregulates expression and activity of the 1b isoform of the plasma membrane calcium pump in immortalized distal kidney tubular cells.
The plasma membrane calcium pump (PMCA) is ubiquitously expressed in calcium transporting epithelia. PMCA is encoded by four distinct genes (PMCA1-4) which can be further posttranscriptionally modified. PMCA1b is the only isoform of PMCA1 expressed in kidney and intestine. Calcitriol upregulates PMCA protein expression and activity and PMCA1 mRNA expression in the intestine. Calcitriol has a similar effect on kidney distal tubule PMCA activity in vivo but the cellular basis for this effect has not been studied. PMCA expression in Madin-Darby bovine kidney (MDBK) cells, a distal kidney tubule cell line, was compared with a proximal tubule (LLC-PK1) and embryonic (HEK 293) kidney cell line. Only MDBK cells express PMCA1b mRNA and PMCA protein. In MDBK cells, calcitriol increased steady state expression of PMCA1b mRNA and protein and upregulated the functional activity of PMCA on calcium transport to a similar degree. Furthermore, calcitriol enhanced PMCA1b mRNA stability. These data are consistent with in vivo localization studies demonstrating the distal kidney tubule localization of PMCA protein. Furthermore, they indicate that calcitriol is an important regulator of PMCA activity in the kidney distal tubule by a pathway that includes translation and posttranscriptional modification of PMCA1b.


Contact-allergic reactions to cosmetics.
Contact-allergic reactions to cosmetics may be delayed-type reactions such as allergic and photo-allergic contact dermatitis, and more exceptionally also immediate-type reactions, that is, contact urticaria. Fragrances and preservative agents are the most important contact allergens, but reactions also occur to category-specific products such as hair dyes and other hair-care products, nail cosmetics, sunscreens, as well as to antioxidants, vehicles, emulsifiers, and, in fact, any possible cosmetic ingredient. Patch and prick testing to detect the respective culprits remains the golden standard for diagnosis, although additional tests might be useful as well. Once the specific allergens are identified, the patients should be informed of which products can be safely used in the future.


Use of trophic magnification factors and related measures to characterize bioaccumulation potential of chemicals.
Recent technical workgroups have concluded that trophic magnification factors (TMFs) are useful in characterizing the bioaccumulation potential of a chemical, because TMFs provide a holistic measure of biomagnification in food webs. The objectives of this article are to provide a critical analysis of the application of TMFs for regulatory screening for bioaccumulation potential, and to discuss alternative methods for supplementing TMFs and assessing biomagnification in cases where insufficient data are available to determine TMFs. The general scientific consensus is that chemicals are considered bioaccumulative if they exhibit a TMF > 1. However, comparison of study-derived TMF estimates to this threshold value should be based on statistical analyses such that variability is quantified and false positive and false negative errors in classification of bioaccumulation potential are minimized. An example regulatory decision-making framework is presented to illustrate the use of statistical power analyses to minimize assessment errors. Suggestions for considering TMF study designs and TMFs obtained from multiple studies are also provided. Alternative bioaccumulation metrics are reviewed for augmenting TMFs and for substituting in situations in which field data for deriving TMFs are unavailable. Field-derived, trophic level-normalized biomagnification factors (BMF(TL) s), biota-sediment accumulation factors (BSAF(TL) s), and bioaccumulation factors (BAF(TL) s) are recommended if data are available, because these measures are most closely related to the biomagnification processes characterized by TMFs. Field- and laboratory-derived BAFs and bioconcentration factors are generally less accurate in predicting biomagnification. However, bioconcentration factors and BAFs remain useful for characterizing bioaccumulation as a result of the transfer of chemicals from abiotic environmental compartments to lower trophic levels. Modeling that incorporates available laboratory and field data should also be considered for augmenting assessments of bioaccumulation potential. Modeling can provide a TMF-focused assessment for new or unreleased chemicals in the absence of field data by estimating TMF values and theoretical relationships between physical-chemical properties and TMF values (quantitative structure-activity relationships). An illustration of the use of physicochemical properties for estimating TMFs is provided. Overall, TMFs provide valuable information regarding bioaccumulation potential and should be incorporated into regulatory decision making following the suggestions outlined in this article.


Occupational relevance of subclavian vein thrombosis in association with thoracic outlet syndrome.
Primary subclavian vein thrombosis ("effort thrombosis") is not generally recognized as a work-related disorder, and more knowledge is required on the particular biomechanical risks. An extensive biomechanical risk analysis was performed for a possible work-related case. A hard-working 43-year-old race-course farrier received successful surgical treatment for subclavian vein thrombosis. No congenital abnormalities were apparent. At work, the farrier spent 75% of his time with his back bent (generally at > 70 degrees) with his right shoulder flexed and abducted, a position that thereby increased the pressure on the subclavian vein. High average (and peak) stress ratings for the neck and shoulder postures are accompanied by high levels of force and considerable repetitiveness. Taken together, these forms of biomechanical overload suggest that the leading cause of the subclavian thrombosis suffered by this farrier could have been occupational. Case-control studies on this neglected topic are needed to investigate possible associations between subclavian vein thrombosis and specific occupational activities.


Placental, maternal serum and amniotic fluid molecular weight forms of inhibin A and pro-alphaC.
Previous studies have identified the presence of unidentified small molecular weight (mol wt) forms of inhibin and the pro-alphaC region of the inhibin alpha subunit in serum from women during late pregnancy. The aim of this study was to investigate if these gestational-related changes in mol wt forms arose from changing placental production. Pooled placental extracts, derived from normal healthy singleton pregnancies in the 1st, 2nd and 3rd trimesters of pregnancy, were fractionated by a combined immunoaffinity chromatography, preparative PAGE and electroelution procedure. Inhibin A, inhibin B and the pro-alphaC region of the inhibin alpha subunit were determined in the eluted fractions by specific ELISAs, with the profiles of immunoactivity characterized in terms of molecular size and percentage recovery. Inhibin B was undetectable in all samples. Mol wt peaks of 36k, 75K and 97K for inhibin A and 29k, 55K and 97K for pro-alphaC were detected in placental extracts across all three trimesters. The relative abundancy of small mol wt inhibin A forms (<30K) present in the placenta increased significantly in the third trimester placenta, increasing from 0.3 per cent in the first trimesters to 6 per cent in the third trimester (P=0.01, chi-squared test). The relative abundances of various mol wt forms of pro-alphaC was similar at all three gestations (P=0.67). In serum, small mol wt inhibin A and pro-alphaC forms accounted for 23.4 per cent and 37.4 per cent of inhibins, respectively, in the third trimester. These data suggest that the presence of small mol wt forms of both inhibin A and pro-alphaC in maternal serum is only partially attributed to placental production and/or secretion. We conclude that inhibin A and pro-alphaC inhibins in maternal serum are processed in late pregnancy by more than one mechanism to form low mol wt circulating forms of, as yet, undetermined structure.


Re-launch of the South African Society of Medical Managers (previously known as the Medical Administrators Group).
Medical management is a recognised specialty in many developing and developed countries, including Australia, India, New Zealand, Pakistan and Sri Lanka. In South Africa it was recognised as a sub-specialty in the 1990s, but this is no longer the case. The South African Society of Medical Managers, in close collaboration with the Division of Medical Management of the College of Public Health Medicine of South Africa, has been working to re-establish the specialty of medical management in South Africa. Well-trained specialist medical managers would play a significant role in the effective and efficient implementation of National Health Insurance and primary healthcare re-engineering through the practice of evidence-based health care, clinical economics and administrative medicine.


Improvements of atherosclerosis and hepatic oxidative stress are independent of exercise intensity in LDLr(-/-) mice.
Cardiovascular diseases are the main causes of death in the Western world and are manifested by atherosclerosis. Depending on its intensity, regular aerobic exercise may be either beneficial or harmful to the atherosclerosis process. The aim of this study was to verify the effects of aerobic exercise training of different intensities on the profile of atherosclerotic lesions and serum lipid, and in the hepatic oxidative balance of low-density lipoprotein receptor-deficient (LDLr(-/-)) mice previously developed with atherosclerosis. All animals were submitted to a three-month high-fat and high-cholesterol diet regime. The animals were then randomly divided into no exercise (G1, n=9), low-intensity aerobic exercise (G2, n=10, 8 weeks of treadmill running, 30 min/day(-1) at 8-10 m/min(-1)) and moderate-intensity aerobic exercise (G3, n=10, 8 weeks of treadmill running, 30 min/day(-1) at 10-16 m/min(-1)) groups. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), and oxidative damage (protein carbonyls and lipid hydroperoxides) were measured. The activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the liver tissue was assessed. G2 (0.015 ± 0.005cm(2)) and G3 (0.014 ± 0.001cm(2)) presented lower aortic fat deposition than G1 (0.039 ± 0.005cm(2)). G2 and G3 exhibited higher HDL-C, TG and CAT activity, but lower lipid peroxidation and carbonyl protein than G1. SOD values were higher in G3 than G2 and G1, and GPx was higher in G2 than in G3 and G1. Our protocols of low- and moderate-intensity aerobic exercise training (30 min daily for 8 weeks) induced similar benefits in LDLr(-/-) mice with atherosclerosis.


Endoscopic assistance in the epidural subtemporal approach and Kawase approach: anatomic study.
Few reports exist in the literature about the use of endoscope assistance in the identification of structures in the posterior fossa. To asses the advantage of endoscopic assistance in the epidural subtemporal and Kawase approaches by studying anatomic exposure and surgical freedom in the posterior cranial fossa. Twelve epidural subtemporal approaches were performed on 6 adult cadaveric heads. On the same specimens, 6 endoscope-assisted subtemporal approaches and 6 Kawase approaches were then performed. At the end of each Kawase approach, endoscope assistance was used. The microsurgical observations were performed with a surgical microscope with magnification ranging from 4 x to 40 x. Endoscopic observations were made with a 0 degrees , 4-mm rod-lens endoscope. Anatomic exposure and surgical freedom were analyzed. Endoscopic assistance during the epidural subtemporal approach increased the anatomic exposure 3 mm superiorly, 20 mm inferiorly, and 10 mm medially from the trigeminal nerve. Surgical freedom was limited in the temporal lobe, the petrous apex, and the trigeminal nerve. The amount of increased anatomic exposure obtained with endoscopic assistance during the Kawase approach was 26 mm inferiorly and medially from the trigeminal nerve. Surgical freedom was limited by the brainstem and the depth of the posterior cranial fossa. The endoscope-assisted subtemporal approach can be useful in visualizing tumor in the posterior fossa. It can help the surgeon in planning further surgical steps through consideration of the size, extension, and adherence of the tumor to surrounding structures. The endoscope-assisted Kawase approach permits maximum anatomic exposure of the posterior cranial fossa, although the deepest neurovascular structures could be better addressed with more direct approaches.


The gene for albicidin detoxification from Pantoea dispersa encodes an esterase and attenuates pathogenicity of Xanthomonas albilineans to sugarcane.
Albicidin phytotoxins are pathogenicity factors in a devastating disease of sugarcane known as leaf scald, caused by Xanthomonas albilineans. A gene (albD) from Pantoea dispersa has been cloned and sequenced and been shown to code for a peptide of 235 amino acids that detoxifies albicidin. The gene shows no significant homology at the DNA or protein level to any known sequence, but the gene product contains a GxSxG motif that is conserved in serine hydrolases. The AlbD protein, purified to homogeneity by means of a glutathione S-transferase gene fusion system, showed strong esterase activity on p-nitrophenyl butyrate and released hydrophilic products during detoxification of albicidins. AlbD hydrolysis of p-nitrophenyl butyrate and detoxification of albicidins required no complex cofactors. Both processes were strongly inhibited by phenylmethylsulfonyl fluoride, a serine enzyme inhibitor. These data strongly suggest that AlbD is an albicidin hydrolase. The enzyme detoxifies albicidins efficiently over a pH range from 5.8 to 8.0, with a broad temperature optimum from 15 to 35 degrees C. Expression of albD in transformed X. albilineans strains abolished the capacity to release albicidin toxins and to incite disease symptoms in sugarcane. The gene is a promising candidate for transfer into sugarcane to confer a form of disease resistance.


Measuring effectiveness of cultural safety education in First Peoples health in university and health service settings.
Background: Cultural Safety is a mandatory training requirement for the 16 regulated health practitioners in Australia. Tools measuring outcomes need to be appropriate for different education and training contexts.Aim: To test refinements to the 25 item Cultural Capability Measurement Tool (CCMT).Methods: Framed by decolonising and relational ways of knowing, being, and doing in the tool development process. New items of the CCMT were generated through engagement with key knowledge holders. New items were piloted with expert reviewers and modified accordingly to produce a 41-item scale. Two online surveys conducted with 875 students and then 276 health professionals were collected for analysis. Exploratory factor analysis and a parallel analysis were conducted.Results: The newly named Ganngaleh nga Yagaleh (GY) tool contained 28 items loaded on 3 factors accounting for 47.95% of variance. Factor 1 (Commitment to Culturally Safe Practice; α = .89) comprised 12 items, Factor 2 (Understanding of History and Power; α = .86) contained 9 items, and Factor 3 (Attitudes, Values, and Beliefs; α = .52) contained 7. Total scale reliability was good (α = .87).Impact statement and conclusion: The GY Scale can be used in education and practice settings. Challenges remain about how educational providers and health services approach cultural safety as a life-long learning journey, and how education and clinical practice embed cultural safety standards. Future directions for use of the GY tool include expanding it for use in other contexts and more explicit separation of what is emerging as a separate scale the 'Keeping Culture Strong' scale which evaluates the unique learning experiences of First Peoples.


Carbon monoxide and biliverdin suppress bovine viral diarrhoea virus replication.
Bovine viral diarrhoea virus (BVDV) causes significant economic losses to the cattle industry worldwide. Previously, we demonstrated that heme oxygenase-1 (HO-1) can inhibit BVDV replication via an unknown molecular mechanism. To elucidate the mechanism involved, we assess whether the HO-1 downstream metabolites carbon monoxide (CO), biliverdin (BV) and iron affect BVDV replication. We treated Madin-Darby bovine kidney (MDBK) cells with an exogenous CO donor, CORM-2. We found that CORM-2 but not its inactive form (iCORM-2) inhibited BVDV replication in a dose-dependent and time duration-dependent manner, suggesting a CO-specific mediation of the CORM-2 antiviral effect. Direct incubation of BVDV with high-dose CORM-2 reduced virus titres, suggesting that CORM-2 attenuates BVDV growth by both physically inactivating virus particles in the extracellular environment and affecting intracellular BVDV replication, but mainly via an intracellular mechanism. Exogenous BV treatment, both post-infection and co-incubation with BVDV, inhibited BVDV replication in a dose-dependent manner, indicating that BV has potent antiviral activity against BVDV. Direct incubation of BVDV with BV had no significant effect on virus titres, indicating that BV is not virucidal and attenuates BVDV growth by affecting intracellular BVDV replication. Furthermore, BV was found to affect BVDV penetration but not attachment. However, increased iron via addition of FeCl3 did not interfere with BVDV replication. Collectively, the results of the present study demonstrate that the HO-1 metabolites BV and CO, but not iron, inhibit BVDV replication. These findings not only provide new insights into the molecular mechanism of HO-1 inhibition of BVDV replication but also suggest potential new control measures for future BVDV infection.


Anisotropic Interlayer Exciton in GeSe/SnS van der Waals Heterostructure.
Stacking two or more two-dimensional materials to form a heterostructure is becoming the most effective way to generate new functionalities for specific applications. Herein, using GW and Bethe-Salpeter equation simulations, we demonstrate the generation of linearly polarized, anisotropic intra- and interlayer excitonic bound states in the transition metal monochalcogenide (TMC) GeSe/SnS van der Waals heterostructure. The puckered structure of TMC results in the directional anisotropy in band structure and in the excitonic bound state. Upon the application of compressive/tensile biaxial strain dramatic variation (∓3%) in excitonic energies, the indirect-to-direct semiconductor transition and the red/blue shift of the optical absorption spectrum are observed. The variations in excitonic energies and optical band gap have been attributed to the change in effective dielectric constant and band dispersion upon the application of biaxial strain. The generation and control over the interlayer excitonic energies can find applications in optoelectronics and optical quantum computers and as a gain medium in lasers.


Dkk1 KO Mice Treated with Sclerostin Antibody Have Additional Increases in Bone Volume.
Dickkopf-1 (DKK1) and sclerostin are antagonists of the Wnt/β-catenin pathway and decreased expression of either results in increased bone formation and mass. As both affect the same signaling pathway, we aimed to elucidate the redundancy and/or compensation of sclerostin and DKK1. Weekly sclerostin antibody (Scl-Ab) was used to treat 9-week-old female Dkk1 KO (Dkk1-/-:Wnt3+/-) mice and compared to Scl-Ab-treated wild-type mice as well as vehicle-treated Dkk1 KO and wild-type animals. While Wnt3 heterozygote (Wnt3+/-) mice show no bone phenotype, Scl-Ab and vehicle-treated control groups of this genotype were included. Specimens were harvested after 3 weeks for microCT, bone histomorphometry, anti-sclerostin immunohistochemistry, and biomechanical testing. Scl-Ab enhanced bone anabolism in all treatment groups, but with synergistic enhancement seen in the cancellous compartment of Dkk1 KO mice (bone volume + 55% Dkk1 KO p < 0.01; + 22% wild type p < 0.05). Scl-Ab treatment produced less marked increases in cortical bone of the tibiae, with anabolic effects similar across genotypes. Mechanical testing confirmed that Scl-Ab improved strength across all genotypes; however, no enhancement was seen within Dkk1 KO mice. Dynamic bone labeling showed that Scl-Ab treatment was associated with increased bone formation, regardless of genotype. Immunohistochemical staining for sclerostin protein indicated no differences in the Dkk1 KO mice, indicating that the increased Wnt signaling associated with DKK1 deficiency was not compensated by upregulation of sclerostin protein. These data suggest complex interactions between Wnt signaling factors in bone, but critically illustrate synergy between DKK1 deficiency and Scl-Ab treatment. These data support the application of dual-targeted therapeutics in the modulation of bone anabolism.


Parkin-dependent and -independent degradation of synaptotagmin-11 in neurons and astrocytes.
Synaptotagmin-11 (Syt11) is associated with schizophrenia and Parkinson's disease (PD) and is a critical substrate of parkin, an E3 ubiquitin ligase linked to PD. Previously we reported that Syt11 regulates multiple membrane trafficking pathways in neurons and glia. However, the regulation of Syt11 degradation remains largely unknown. As the ubiquitin-proteasome pathway (UPP) plays crucial roles in protein degradation and quality control, we investigated UPP-dependent Syt11 degradation in this study. We found that Syt11 is a short-lived protein with a half-life of 1.49 h in the presence of a protein synthesis inhibitor cycloheximide and is mainly degraded by UPP in neurons. The degradation was further accelerated under sustained neuronal activity and was parkin-dependent. Interestingly, Syt11 had a faster turnover in astrocytes with a half-life of 0.58 h, and UPP partially contributed to its degradation. Mechanical stress applied on astrocytes by hypoosmotic treatment led to reduced Syt11 protein level but increased parkin level. However, the degradation of Syt11 was parkin-independent under both isoosmotic and hypoosmotic condition. Altogether, our results revealed active and distinct proteolytic regulation of Syt11 in neurons and astrocytes.


Establishing an independent mobile health program for chronic disease self-management support in bolivia.
Mobile health (m-health) work in low- and middle-income countries (LMICs) mainly consists of small pilot programs with an unclear path to scaling and dissemination. We describe the deployment and testing of an m-health platform for non-communicable disease (NCD) self-management support in Bolivia. Three hundred sixty-four primary care patients in La Paz with diabetes or hypertension completed surveys about their use of mobile phones, health and access to care. One hundred sixty-five of those patients then participated in a 12-week demonstration of automated telephone monitoring and self-management support. Weekly interactive voice response (IVR) calls were made from a platform established at a university in La Paz, under the direction of the regional health ministry. Thirty-seven percent of survey respondents spoke indigenous languages at home and 38% had six or fewer years of education. Eighty-two percent had a mobile phone, 45% used text messaging with a standard phone, and 9% had a smartphone. Smartphones were least common among patients who were older, spoke indigenous languages, or had less education. IVR program participants completed 1007 self-management support calls with an overall response rate of 51%. IVR call completion was lower among older adults, but was not related to patients' ethnicity, health status, or healthcare access. IVR health and self-care reports were consistent with information reported during in-person baseline interviews. Patients' likelihood of reporting excellent, very good, or good health (versus fair or poor health) via IVR increased during program participation and was associated with better medication adherence. Patients completing follow-up interviews were satisfied with the program, with 19/20 (95%) reporting that they would recommend it to a friend. By collaborating with LMICs, m-health programs can be transferred from higher-resource centers to LMICs and implemented in ways that improve access to self-management support among people with NCDs.


The bundle-forming pili of enteropathogenic Escherichia coli: transcriptional regulation by environmental signals.
The bundle-forming pili (BFP) of enteropathogenic Escherichia coil (EPEC) are required for the development of circumscribed colonies of bacteria attached to the surfaces of cultured epithelial cells, a process termed the localized adherence (LA) phenotype. Similar lesions are evident in jejunal biopsies from EPEC-infected children. BFP production is not constitutive, but instead occurs upon transfer of bacteria from nutrient broth to tissue culture media, indicating that the expression of BFP may be environmentally regulated. To learn more about how BFP protein expression is induced during epithelial-cell adherence, bfpA-cat transcriptional fusions and northern blot analyses were employed to monitor bfpA expression as a function of environmental signals and growth kinetics. bfpA expression was found to be regulated at the transcriptional level, and to require a separate locus on the EPEC adherence factor (EAF) plasmid. Expression occurred selectively during exponential-growth phase and was greatest between 35 and 37 degrees C, and in the presence of calcium. Ammonium (20 mM) significantly reduced bfpA mRNA and protein expression and the development of the LA phenotype. Analysis of the bfpA upstream sequence and identification of the transcription initiation site revealed a conventional sigma (70)-dependent promoter and an AT-rich tract that might affect promoter activity. Taken together, these findings further support the pathogenic role of BFP by explaining how BFP production would commence in the small intestine and terminate in the colon and in external habitats.


An orthogonal system for heterologous expression of actinobacterial lasso peptides in Streptomyces hosts.
Lasso peptides are ribosomally synthesized and post-translationally modified peptides produced by bacteria. They are characterized by an unusual lariat-knot structure. Targeted genome scanning revealed a wide diversity of lasso peptides encoded in actinobacterial genomes, but cloning and heterologous expression of these clusters turned out to be problematic. To circumvent this, we developed an orthogonal expression system for heterologous production of actinobacterial lasso peptides in Streptomyces hosts based on a newly-identified regulatory circuit from Actinoalloteichus fjordicus. Six lasso peptide gene clusters, mainly originating from marine Actinobacteria, were chosen for proof-of-concept studies. By varying the Streptomyces expression hosts and a small set of culture conditions, three new lasso peptides were successfully produced and characterized by tandem MS. The newly developed expression system thus sets the stage to uncover and bioengineer the chemo-diversity of actinobacterial lasso peptides. Moreover, our data provide some considerations for future bioprospecting efforts for such peptides.


Cholera in a developing megacity; Karachi, Pakistan.
Despite rapid urbanization and increasing affluence in Karachi, cases of cholera are frequent. We analysed computerized isolation data from the AKUH Clinical Microbiology Laboratory, Karachi, from 1990-6 to examine microbiological, temporal and demographic trends in Vibrio cholerae infections. During this period 888 strains of V. cholerae (566 V. cholerae serogroup O1, and 204 V. cholerae serogroup O139) were isolated from specimens from 886 patients; 214/464 were adult inpatients, and 250/464 paediatric inpatients, the remaining 422 outpatients. Isolations peaked between June and August. Overlapping epidemics occurred in 1993 and 1994 of serogroup O1 (May to August), and serogroup O139 (August to October). All ages and social and economic strata were affected. Forty-four percent of all isolates were from children under the age of 5 years. The mean age of all patients with serogroup O1 infections was 19.6 years (+/-0.9) compared with 367 (+/-1.7) for serogroup O139 infections (P < 0.0001, t test). More than a quarter (27%) of all serogroup O1 isolates were from babies under 2 years of age. One patient had a serogroup O1 infection followed by a serogroup O139 infection 1 year later. Another patient was infected with serogroup O1 strains 5 years apart. Emergence of resistant strains was observed, but by 1996 serogroup O139 had disappeared. An aquatic organism, cholera nevertheless continues to take its toll in this city of 11 million situated in a desert.


Learning orthopaedics: assessing medical students' experiences of interprofessional training in an orthopaedic clinical education ward.
Interprofessional training is becoming commonplace in undergraduate medical education. Orthopaedics is considered to be a setting that offers good opportunities for interprofessional training. Curriculum overload is a common problem, which has to be addressed with respect to content. The aim of this study was to assess medical students' experiences of interprofessional care during their orthopaedic training. Over a two-week period, medical, nursing, physiotherapy and occupational therapy students trained together in teams in an orthopaedic ward (Clinical Education Ward, CEW). A questionnaire was distributed to assess the impact of this new curriculum on medical students. A patient-satisfaction questionnaire was also administered to assess patients' satisfaction with the treatment provided by students at the CEW. In general, the medical students were satisfied with the interprofessional course in the CEW. Of the 178 medical students who took the course, 134 (75%) responded to the questionnaire. Total time devoted to orthopaedics was reported to be between 7 - 44% (mean). The total time regarding medical tasks was reported to be between 57 - 71% (mean). Results from the patient-satisfaction questionnaire showed that patients perceived CEW as highly satisfactory. The medical students reported generally satisfactory experiences of interprofessional orthopaedic training in general. In an interprofessional training context, professional supervision and role modeling takes on added importance, and may be regarded as essential ingredients in helping students to learn effectively within an authentic clinical setting.


Review: PrP 106-126 - 25 years after.
A quarter of a century ago, we proposed an innovative approach to study the pathogenesis of prion disease, one of the most intriguing biomedical problems that remains unresolved. The synthesis of a peptide homologous to residues 106-126 of the human prion protein (PrP106-126), a sequence present in the PrP amyloid protein of Gerstmann-Sträussler-Scheinker syndrome patients, provided a tractable tool for investigating the mechanisms of neurotoxicity. Together with several other discoveries at the beginning of the 1990s, PrP106-126 contributed to underpin the role of amyloid in the pathogenesis of protein-misfolding neurodegenerative disorders. Later, the role of oligomers on one hand and of prion-like spreading of pathology on the other further clarified mechanisms shared by different neurodegenerative conditions. Our original report on PrP106-126 neurotoxicity also highlighted a role for programmed cell death in CNS diseases. In this review, we analyse the prion research context in which PrP106-126 first appeared and the advances in our understanding of prion disease pathogenesis and therapeutic perspectives 25 years later.


Unusual delayed presentation of superior mesenteric artery syndrome following scoliosis correction surgery-a case report and review of literature.
Superior mesenteric artery (SMA) syndrome secondary to extrinsic compression of third part of duodenum is an uncommon complication following scoliosis surgery. It is imperative to diagnose this presentation at an earlier stage as it can be a potentially life threatening complication. If the diagnosis is missed or delayed, the mortality rate can be as high as 33% due to fatal complications like aspiration pneumonia, acute gastric rupture and cardiovascular collapse. We present a 13-year-old patient who was diagnosed with SMA syndrome in the late post-operative period (5.1 weeks) following scoliosis correction surgery. A barium meal and follow-through confirmed the diagnosis of SMA syndrome. She was managed conservatively with which she recovered uneventfully. Such late presentations are very uncommon. In addition, we have also briefly reviewed the pertinent literature. It is essential that we identify high risk patients preoperatively so that we could optimize them with proper intensive dietary supplementation. Postoperatively, a high index of suspicion needs to be retained to identify this syndrome at an early stage so that conservative management may be initiated with good clinical outcome. SMA syndrome can be potentially life threatening when the diagnosis is missed or delayed.


A study of the role of the hexose monophosphate pathway with respect to fatty acid biosynthesis in sporulation of Saccharomyces cerevisiae.
13C NMR was used to study the pattern of label incorporation from [2-13C]acetate into trehalose during sporulation in Saccharomyces cerevisiae. A wild-type strain and a strain homozygous for the zwf1 mutation (which affects glucose-6-phosphate dehydrogenase) were used. In the wild-type it was possible to deduce the cycling of glucose 6-phosphate around the hexose monophosphate pathway whilst in the mutant strain this did not occur. The requirement of the hexose monophosphate pathway for providing NADPH for fatty acid biosynthesis was examined using 13C NMR and GC/MS. The wild-type strain produced a typical profile of fatty acids with palmitoleic acid being the most abundant whereas the mutant contained only one-quarter the amount of total fatty acid. As zwf1 homozygous diploids are able to sporulate this indicates that the large amount of fatty acid biosynthesis observed in sporulation of wild-type strains is not essential to the process.


Avian top predator and the landscape of fear: responses of mammalian mesopredators to risk imposed by the golden eagle.
Top predators may induce extensive cascading effects on lower trophic levels, for example, through intraguild predation (IGP). The impacts of both mammalian and avian top predators on species of the same class have been extensively studied, but the effects of the latter upon mammalian mesopredators are not yet as well known. We examined the impact of the predation risk imposed by a large avian predator, the golden eagle (Aquila chrysaetos, L.), on its potential mammalian mesopredator prey, the red fox (Vulpes vulpes, L.), and the pine marten (Martes martes, L.). The study combined 23 years of countrywide data from nesting records of eagles and wildlife track counts of mesopredators in Finland, northern Europe. The predation risk of the golden eagle was modeled as a function of territory density, density of fledglings produced, and distance to nearest active eagle territory, with the expectation that a high predation risk would reduce the abundances of smaller sized pine martens in particular. Red foxes appeared not to suffer from eagle predation, being in fact most numerous close to eagle nests and in areas with more eagle territories. This is likely due to similar prey preferences of the two predators and the larger size of foxes enabling them to escape eagle predation risk. Somewhat contrary to our prediction, the abundance of pine martens increased from low to intermediate territory density and at close proximity to eagle nests, possibly because of similar habitat preferences of martens and eagles. We found a slightly decreasing trend of marten abundance at high territory density, which could indicate that the response in marten populations is dependent on eagle density. However, more research is needed to better establish whether mesopredators are intimidated or predated by golden eagles, and whether such effects could in turn cascade to lower trophic levels, benefitting herbivorous species.


Human in vitro models for understanding mechanisms of autism spectrum disorder.
Early brain development is a critical epoch for the development of autism spectrum disorder (ASD). In vivo animal models have, until recently, been the principal tool used to study early brain development and the changes occurring in neurodevelopmental disorders such as ASD. In vitro models of brain development represent a significant advance in the field. Here, we review the main methods available to study human brain development in vitro and the applications of these models for studying ASD and other psychiatric disorders. We discuss the main findings from stem cell models to date focusing on cell cycle and proliferation, cell death, cell differentiation and maturation, and neuronal signaling and synaptic stimuli. To be able to generalize the results from these studies, we propose a framework of experimental design and power considerations for using in vitro models to study ASD. These include both technical issues such as reproducibility and power analysis and conceptual issues such as the brain region and cell types being modeled.


Atrial myxomas: pathologic types, tumor location, and presenting symptoms.
Atrial myxoma is the most common cardiac neoplasm. Although not widely reported, two anatomic types have been observed: solid and papillary. We examined whether differences in gross or microscopic appearance and location correlated with symptomatology, specifically congestive heart failure (CHF), neurologic symptoms, and embolic events. We performed a retrospective review of atrial myxomas removed from 1972 to 2002, recording the clinical presentation, diagnostic modality, tumor location, gross, and microscopic features for each patient. Twenty-six patients (16 females and 10 males) had atrial myxomas excised. Two patients (one female and one male) were excluded due to unavailable pathologic slides. In 24 patients there were 15 solid and 9 papillary tumors. CHF was more prevalent in solid myxomas, while neurologic symptoms and embolic events were more common in papillary tumors. Tumor location further correlated with presenting symptoms. Ninety-two percent of patients presenting with CHF had tumors attached to the atrial septum. Extraseptal myxomas more frequently presented with neurologic (80% vs. 29%) and embolic features (50% vs. 25%). All patients exhibiting clefted tumor surface had a history of embolization. A higher percentage of solid myxomas (93%) showed hemorrhage within the tumor than with papillary (56%). CHF was more common with solid myxomas, and neurologic and embolization events were more common in the papillary type. Septal tumor location showed strong association with CHF, while extraseptal location correlated with neurologic events. We speculate that the various gross and microscopic patterns reflect secondary changes within these neoplasms over the course of their natural history.


Evidence in the aesthetic surgical literature over the past decade: how far have we come?
Over the past decade, the concepts of evidence-based medicine have become commonplace in surgery. The authors aimed to categorize level of evidence in the aesthetic surgical literature over three intervals during a 10-year period, and to compare this to other surgical specialties. The authors also aimed to assess the quality and predictor factors of higher level evidence. Clinical aesthetic surgical literature published in the highest impact journals in 2000, 2005, and 2009/2010 was reviewed. Articles were evaluated for journal, date of publication, number and origin of authors, area, centers of collaboration, number of subjects, study subtype, and level of evidence. Eligible level I studies were evaluated using the Detsky Quality Scale. Five thousand eighty-eight articles were screened, and 526 met eligibility criteria. Thirteen studies (2.5 percent) were level I, 72 (13.7 percent) were level II, 57 (10.8 percent) were level III, 263 (50 percent) were level IV, and 121 (23 percent) were level V. Detsky Quality Scale scores averaged 68.4 percent (minimum, 40 percent; maximum 85 percent). Publications of larger sample size (p = 0.01) and published in Plastic and Reconstructive Surgery (p = 0.02) were significantly associated with higher levels of evidence (levels I/II). The ratio of level I evidence to other levels (levels II to V) in aesthetic surgery compared favorably with oral and plastic surgery; however, ratios were eightfold, sixfold, and fivefold less than those reported in ophthalmology, otolaryngology, and orthopedic surgery, respectively. Over the past decade, the mean level of evidence in the aesthetic literature has improved. However, level I evidence is the least represented, and these studies have methodologic limitations.


Convergence insufficiency and its current treatment.
Considerable uncertainty and controversy has existed concerning the management of convergence insufficiency. Only recently there have been significant scientific studies published that compare the effectiveness of the commonly prescribed treatments. This paper reviews the most recent research and literature on convergence insufficiency and its treatment. The first large-scale placebo-controlled, randomized clinical trials to study the various treatments of convergence insufficiency have recently been published. Current research compares the effectiveness of base-in prism glasses, pencil push-ups, and vision therapy in reducing the signs and symptoms of convergence insufficiency and suggests that orthoptic therapy is the most efficacious treatment for convergence insufficiency. Intensive orthoptic therapy is the treatment of choice for convergence insufficiency. Pencil push-ups and use of accommodative targets have a role in the treatment of convergence insufficiency when used as part of a more intensive orthoptic program. Base-in prism glasses should be reserved for reduction of symptoms in the presbyopic population.