Delayed sternal closure: an effective procedure for life-saving in open-heart surgery.
To determine the incidence, short term survival and safety of delayed sternal closure following open-heart operation due to myocardial edema, non-surgical bleeding and malignant arrhythmia. We retrospectively reviewed our medical records to identify the patients who underwent delayed sternal closure following open-heart operation and recorded morbidity, mortality postoperative complications of these patients. Among 2698 patients who underwent on- pump cardiac surgery, the sternum was left open in 46 (1.7%) patients, 31 men and 15 women, ranging in age from 2 to 73 years (mean 57.0+/-7.6 years). In 39 patients sternum was left opened following the initial operation and in 7 patients sternum was re-opened due to bleeding or hemodynamic instability after initial surgery. Statistical analysis was accomplished using Chi-square test, Mann Whitney U test and analysis of variances for repeated measurements. The operative procedures were classified as elective in 24 (52.8%), emergency in 10 (22%), urgent in 7 (15.4%), and redo cardiac operations in 5 patients (11%). Bleeding (n=21), hemodynamic instability (n=16), arrest (n=5), and arrhythmia (n=4) were the reasons of delayed sternal closure. The patients had an open sternum for 3.48+/-0.35 days. Time to discharge was 21.5+/-1.6 days after operation and 17.6+/-1.6 days after sternal closure. Mortality within 30 days was 23.9% (7 patients died before closure and the remaining 4 after closure). Complications were mediastinitis (n=2), minor wound infection (n=3) and renal failure (n=5). Delayed sternal closure is a safe and simple method for treating bleeding, arrhythmia and myocardial edema following on pump cardiac surgery. It is anticipated that as cardiac surgeons become more familiar with the technique of delayed sternal closure, the frequency of its use following on pump cardiac surgery may increase.


The influence of the COVID-19 pandemic on the hedging functionality of Chinese financial markets.
In this paper, we investigate both constant and time-varying hedge ratios in terms of the effectiveness of CSI300 index futures during the COVID-19 crisis. Using naïve, OLS and EC/ROLS strategies to estimate constant hedge ratios, results indicate that the CSI300 spot index presents decreased effectiveness using the naïve hedging strategy; however, increased effectiveness of OLS and EC hedge ratios are identified. Differential behaviour is identified when considering five newly introduced COVID-19 concept-based stock indices. Time-varying hedge ratios indicate the weakened effectiveness, ranging between 20% and 40% variance reduction. Evidence suggests that the capability of the CSI300 index futures to hedge against the risks of the COVID-19 is impaired, regardless of whether constant or time-varying hedge ratios are used. Such results provide important implications to both local and foreign investors in the Chinese stock market.


Chromosomal abnormalities in systemic amyloidosis.
Primary systemic amyloidosis (AL) is a plasma cell disorder characterized by deposition of monoclonal light chains in different organ systems. Although multiple and complex numerical chromosomal abnormalities have been described in patients with multiple myeloma, it is currently unknown whether such changes occur in systemic amyloidosis. Bone marrow samples from 21 patients with AL were studied by standard cytogenetics and interphase fluorescence in situ hybridization (FISH) for the presence of numerical chromosomal abnormalities. We tested for six chromosomes (7, 11, 9, 15, 18 and X) using centromere-specific probes. The monoclonal plasma cells were identified by simultaneous fluorescent staining of the monotypic cytoplasmic immunoglobulin. We compared these results with those obtained from 19 patients with monoclonal gammopathy of undetermined significance (MGUS) and normal controls. Multiple numerical chromosomal abnormalities were detected in AL by interphase FISH, including trisomy of chromosomes 7 (42%), 9 (52%), 11 (47%), 15 (39%), 18 (33%) and X (13% in women and 54% in men). Monosomy of chromosome 18 was seen in 72% of cases. Previous exposure to alkylator therapy did not appear to correlate with these abnormalities. No significant difference was observed in the prevalence of these abnormalities between AL and MGUS. Multiple chromosomal numerical abnormalities were detected by interphase FISH analysis in patients with AL, especially monosomy of chromosome 18. Aneuploidy in the monotypic plasma supports a neoplastic nature for the disorder.


The role of a decision-support smartphone application in enhancing community health volunteers' effectiveness to improve maternal and newborn outcomes in Nairobi, Kenya: quasi-experimental research protocol.
Improving maternal and newborn survival remains major aspirations for many countries in the Global South. Slum settlements, a result of rapid urbanisation in many developing countries including Kenya, exhibit high levels of maternal and neonatal mortality. There are limited referral mechanisms for sick neonates and their mothers from the community to healthcare facilities with ability to provide adequate care. In this study, we specifically plan to develop and assess the added value of having community health volunteers (CHVs) use smartphones to identify and track mothers and children in a bid to reduce pregnancy-related complications and newborn deaths in the urban slums of Kamukunji subcounty in Nairobi, Kenya. This is a quasi-experimental study. We are implementing an innovative, mHealth application known as mobile Partnership for Maternal, Newborn and Child Health (mPAMANECH) which uses dynamic mobile phone and web-portal solutions to enable CHVs make timely decisions on the best course of action in their management of mothers and newborns at community level. The application is based on existing guidelines and protocols in use by CHVs. Currently, CHVs conduct weekly home visits and make decisions from memory or using unwieldy manual tools, and thus prone to making errors. mPAMANECH has an in-built algorithm that makes it easier, faster and more likely for CHVs to make the right management decision. We are working with a network of selected CHVs and maternity centres to pilot test the tool. To measure the impact of the intervention, baseline and end-line surveys will be conducted. Data will be obtained through qualitative and quantitative methods. Ethical approval for the study was obtained from the African Medical Research Foundation. Key messages from the results will be packaged and disseminated through meetings, conference presentations, reports, fact sheets and academic publications to facilitate uptake by policy-makers.


The anatomy of neurons projecting to the corpus cardiacum from the larval brain of the tobacco hornworm, Manduca sexta (L.).
Retrograde cobalt filling followed by silver intensification revealed new features of the anatomy of neurons which project from the brain to the corpus cardiacum (CC) of the fifth instar larva of Manduca sexta. Filling via the fused nervi corporis cardiaci (NCC) I + II demonstrated four groups of cell bodies (Ia, Ib, II, and III) previously described by Nijhout (1975), plus three major axonal tracts (A, B, and C), and four previously unobserved areas of dendritic branching, dendritic fields (DF) 1, 2, 3, and 4. Tract C is unusual in that it originates from cell bodies on the side contralateral to the filled nerve, travels ventrally and crosses over to the ipsilateral side where it turns dorsally, forming a hook in the center of the brain. It then turns ventrally again to join with tract A. DF 1 and 2 are located ventrally on the ipsilateral and contralateral sides of the brain respectively. DF3 and 4 are situated in the dorsal protocerebrum, on the ipsilateral and contralateral sides respectively. Fills via the NCC III revealed one cell group (IV) and a fifth dendritic field (DF 5). Simultaneous fills of both the fused NCC I + II and the NCC III showed an overlapping of DF 1 and 5, indicating the possibility of synaptic connections between these two fields.


Physical exercise habits are related with reduced prevalence of falling among elderly women in China.
Although some studies have examined the association between exercise and falls, most have focused on specific exercises, and the results have been inconsistent. In addition, there is a lack of evidence on elderly Chinese women who have different living and exercise habits compared to those in other countries. Therefore, this study aimed to investigate whether physical exercise is associated with falls in elderly Chinese women. This cross-sectional study included 1429 elderly Chinese women with a mean age of 69.2 years. Information on physical exercise habits and fall experiences was collected using a self-report questionnaire. Logistic regression models were used to analyze the association between physical exercise habits and falls. The results showed that 15% participants had a fall in the past year. After adjusting for confounding factors, the odd ratios (ORs) and 95% Confidence Intervals (CIs) for fall experiences across categories of exercise frequency were as follow: 1 (reference) for no exercise behavior, 0.50 (0.29, 0.85) for exercise 1 to 5 times a week, and 0.37 (0.25, 0.55) for exercise more than 6 times a week. Furthermore, the ORs (95% CIs) across categories of exercise insistence were 1 (reference) for less than 1 year, 0.78 (0.37, 1.65) for 1 to 3 years, and 0.38 (0.20, 0.74) for more than 3 years. In terms of exercise duration, the ORs (95% CIs) for < 1 h/day, 1-2 h/day, and > 2 h/day were 1 (reference), 0.85 (0.53, 1.36), and 2.80 (1.30, 6.05). Unlike other variables, longer exercise duration was associated unfavorably with falls. Physical exercise habits were associated with falls in elderly Chinese women. Keeping a proper exercise habit may contribute to lower risk of falling in elderly women.


[The eye as an object of forensic medical identification].
The present review is focused on the literature publications concerning various aspects of significance of the human eye as an object of forensic medical identification. The data discussed in this review may provide a basis for the development of the algorithm of forensic ophthalmological studies of both living subjects and corpses; moreover, they can be used to determine the human age from the morphometric characteristics of eye tissues for the purpose of forensic medicine and criminal investigations. The authors emphasize the importance of purpose-oriented studies of various eye structures as a source of additional information for the application of the existing methods designed for personality identification. Changes in the eyes associated with congenital defects and ageing, surgical interventions, and their complications are discussed with special reference to their application in the practical work of forensic medical experts.


Closed-Loop Plantar Cutaneous Augmentation by Electrical Nerve Stimulation Increases Ankle Plantarflexion During Treadmill Walking.
Ankle plantarflexion plays an important role in forward propulsion and anterior-posterior balance during locomotion. This component of gait is often critically impacted by neurotraumas and neurological diseases. We hypothesized that augmenting plantar cutaneous feedback, via closed-loop distal-tibial nerve stimulation, could increase ankle plantarflexion during walking. To test the hypothesis, one intact rat walked on a motorized treadmill with implanted electronic device and electrodes for closed-loop neural recording and stimulation. Constant-current biphasic electrical pulse train was applied to distal-tibial nerve, based on electromyogram recorded from the medial gastrocnemius muscle, to be timed with the stance phase. The stimulation current threshold to evoke plantar cutaneous feedback was set at 30 μA (1·T), based on compound action potential evoked by stimulation. The maximum ankle joint angle at plantarflexion, during the application of stimulation currents of 3.3·T and 6.6·T, respectively, was increased from 149.4° (baseline) to 165.4° and 161.6°. The minimum ankle joint angle at dorsiflexion was decreased from 59.4° (baseline) to 53.1°, during the application of stimulation currents of 3.3·T, but not changed by 6.6·T. Plantar cutaneous augmentation also changed other gait kinematic parameters. Stance duty factor was increased from 51.9% (baseline) to 65.7% and 64.0%, respectively, by 3.3·T and 6.6·T, primarily due to a decrease in swing duration. Cycle duration was consistently decreased by the stimulation. In the control trial after two stimulation trials, a strong after-effect was detected in overall gait kinematics as well as ankle plantarflexion, suggesting that this stimulation has the potential for producing long-term changes in gait kinematics.


Memory storage and effect of repeated treatment with a new antidepressant drug: rubidium chloride.
Following 15 days' treatment with saline, 48 mg/kg rubidium chloride, 5 mg/kg imipramine hydrochloride, 10 mg/kg sodium phenobarbitone, 1000 mg/kg piracetam, or 0.20 mg/kg strychnine nitrate all administered intraperitoneally, mice were evaluated by habituation of exploratory activity using an open-field apparatus. In control animals a significant (P less than 0.05) decrease in open-field responses (ambulation, rearing and defaecation) was seen following a 1-day intersession interval and there was no retention of exploratory activity after a 5-day intersession interval. Administration of imipramine or phenobarbitone for 15 days was found to impair retention of memory after 1 day, whereas treatment with rubidium chloride, piracetam, or strychnine for 15 days improve retention after a 5-day intersession interval.


Effects of omega-3 essential fatty acids against formaldehyde-induced nephropathy in rats.
The aim of this study was to examine the toxicity of formaldehyde (FA) on the kidney and the protective effects of omega-3 essential fatty acids against these toxic effects. Twenty-one male Wistar rats were divided into three groups. Rats in Group I comprised the controls, while the rats in Group II were injected every other day with FA. Rats in Group III received omega-3 fatty acids daily while exposed to FA. At the end of the 14-day experimental period, all rats were killed by decapitation and the kidneys removed. Some of the kidney tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) levels. The remaining kidney tissue specimens were used for light microscopic evaluation. The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in rats treated with FA compared with those of the controls. Furthermore, in the microscopic examination of this group, glomerular and tubular degeneration, vascular congestion and tubular dilatation were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered omega-3 fatty acids while exposed to FA. Additionally, kidney damage caused by FA was decreased and structural appearance was similar to that of the control rats in this group. In conclusion, it was determined that FA-induced kidney damage was prevented by administration of omega-3 essential fatty acids.


RICOPILI: Rapid Imputation for COnsortias PIpeLIne.
Genome-wide association study (GWAS) analyses, at sufficient sample sizes and power, have successfully revealed biological insights for several complex traits. RICOPILI, an open-sourced Perl-based pipeline was developed to address the challenges of rapidly processing large-scale multi-cohort GWAS studies including quality control (QC), imputation and downstream analyses. The pipeline is computationally efficient with portability to a wide range of high-performance computing environments. RICOPILI was created as the Psychiatric Genomics Consortium pipeline for GWAS and adopted by other users. The pipeline features (i) technical and genomic QC in case-control and trio cohorts, (ii) genome-wide phasing and imputation, (iv) association analysis, (v) meta-analysis, (vi) polygenic risk scoring and (vii) replication analysis. Notably, a major differentiator from other GWAS pipelines, RICOPILI leverages on automated parallelization and cluster job management approaches for rapid production of imputed genome-wide data. A comprehensive meta-analysis of simulated GWAS data has been incorporated demonstrating each step of the pipeline. This includes all the associated visualization plots, to allow ease of data interpretation and manuscript preparation. Simulated GWAS datasets are also packaged with the pipeline for user training tutorials and developer work. RICOPILI has a flexible architecture to allow for ongoing development and incorporation of newer available algorithms and is adaptable to various HPC environments (QSUB, BSUB, SLURM and others). Specific links for genomic resources are either directly provided in this paper or via tutorials and external links. The central location hosting scripts and tutorials is found at this URL: https://sites.google.com/a/broadinstitute.org/RICOPILI/home. Supplementary data are available at Bioinformatics online.


Cercaria-schistosomulum surface transformation of Trichobilharzia szidati and its putative immunological impact.
Schistosome cercariae of the genus Trichobilharzia are the causative agent of swimmers' itch. In order to characterize the changes in parasites during and after the penetration of the host skin, in vitro and in vivo (in ducks and mice) transformations of T. szidati cercariae to schistosomula were performed. Ultrastructural observation revealed that cercariae possess a simple outer tegumental membrane with a thick glycocalyx. As with human schistosomes, the latter structure disappears during transformation and a new double membrane with putative protective function is formed. Our biochemical and immunological observations showed that the carbohydrate-rich glycocalyx of cercariae is readily bound by lectins and antibodies. The in vitro transformation to schistosomula can be detected by enhanced reactivity of 2 lectin probes (PNA and ConA) with the surface. The in vivo-transformed (skin and lung) schistosomula appear to have few surface ligands for the 12 lectin probes being tested. Similarly, the cercarial surface and its remnants on the in vitro-produced schistosomula is recognized by sera from immunized mice and humans with cercarial dermatitis; the tissue schistosomula fail to react with these antibodies. The loss of surface targets as a part of parasite immune evasion within the host is discussed.


Towards Better Culturally Tailored Cardiometabolic Prevention Among the South-Asian Surinamese in the Netherlands.
Objectives: To gain insight in the motives and determinants for the uptake of healthy lifestyles by South-Asian Surinamese people to identify needs and engagement strategies for healthy lifestyle support. Methods: We used a mixed-method design: first, focus groups with South-Asian Surinamese women; second, a questionnaire directed at their social network, and third, interviews with health professionals. Qualitative content analysis, basic statistical analyses and triangulation of data were applied. Results: Sixty people participated (n = 30 women, n = 20 social network, n = 10 professionals). Respondent groups reported similar motives and determinants for healthy lifestyles. In general, cardiometabolic prevention was in line with the perspectives and needs of South-Asian Surinamese. However, there seems to be a mismatch too: South-Asian Surinamese people missed a culturally sensitive approach, whereas professionals experienced difficulty with patient adherence. Incremental changes to current lifestyles; including the social network, and an encouraging approach seem to be key points for improvement of professional cardiometabolic prevention. Conclusion: Some key points for better culturally tailoring of preventive interventions would meet the needs and preferences of the South-Asian Surinamese living in the Netherlands.


Brief Overview on Bio-Based Adhesives and Sealants.
Adhesives and sealants (AS) are materials with excellent properties, versatility, and simple curing mechanisms, being widely used in different areas ranging from the construction to the medical sectors. Due to the fast-growing demand for petroleum-based products and the consequent negative environmental impact, there is an increasing need to develop novel and more sustainable sources to obtain raw materials (monomers). This reality is particularly relevant for AS industries, which are generally dependent on non-sustainable fossil raw materials. In this respect, biopolymers, such as cellulose, starch, lignin, or proteins, emerge as important alternatives. Nevertheless, substantial improvements and developments are still required in order to simplify the synthetic routes, as well as to improve the biopolymer stability and performance of these new bio-based AS formulations. This environmentally friendly strategy will hopefully lead to the future partial or even total replacement of non-renewable petroleum-based feedstock. In this brief overview, the general features of typical AS are reviewed and critically discussed regarding their drawbacks and advantages. Moreover, the challenges faced by novel and more ecological alternatives, in particular lignocellulose-based solutions, are highlighted.


MR-guided RF thermal ablation of the kidney in a porcine model.
The purpose of the study was to evaluate the ability of MR imaging to reveal RF interstitial thermotherapy in the porcine kidney, as a model for future human trials, and to provide guidance for RF probe insertion. Ten MR-guided RF ablations were performed in the kidneys of three pigs. A 17-gauge monopolar RF probe electrode was inserted into the renal cortex using MR guidance, and RF was applied for 10 min. After postprocedure imaging (T2-weighted, turbo short inversion time inversion recovery [STIR], and T1-weighted sequences), the kidneys were harvested for pathologic examination. Successful RF probe placement was accomplished in all cases; the interventional procedure time for probe insertion ranged from 4 to 15 min. The thermal lesion size varied from 7 to 14 mm perpendicular to the probe track and was best seen on turbo STIR images. Turbo STIR had the highest renal cortex-to-RF thermal lesion contrast-to-noise ratio with an average of 4.4 +/- 3.5. Turbo STIR imaging never overestimated pathologic lesion diameter with a mean difference of 1.5 +/- 1.4 mm. Three subcapsular hematomas occurred. which could be detected immediately on postprocedure imaging. MR-guided RF thermal ablation in the porcine kidney was found to be feasible, but minor complications occurred. Induced thermal lesion size was best monitored using turbo STIR images. In the future, RF ablation may offer an alternative treatment option for renal cancer.


Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation.
Aripiprazole lauroxil (AL), a new long-acting injectable antipsychotic, demonstrated safety and efficacy in treating acute exacerbation symptoms of schizophrenia in a 12-week placebo-controlled trial of two doses of AL (441mg and 882mg) administered every 4weeks. We performed a post hoc analysis of this trial to evaluate the efficacy of AL in the subgroup of patients with severe psychotic symptoms, defined as those with baseline Positive and Negative Syndrome Scale (PANSS) Total score above the median score of 92 (n=309). Change from baseline to Day 85 in PANSS Total score; Positive, Negative, and General Psychopathology subscale scores; and overall response rate were assessed. Statistically significant and clinically meaningful improvements in PANSS Total score were demonstrated with AL 441mg and AL 882mg, with placebo-adjusted differences of -14.7 (p<0.0001) and -16.6 (p<0.0001), respectively. Significant and clinically meaningful findings with both doses of AL were also demonstrated for the PANSS subscales and responder rates. Overall responder rates at Day 85 were significantly greater for AL 441mg (49%; p<0.001) and 882 mg (61%; p<0.001) groups vs. placebo (18%). Common adverse events (>5%) were schizophrenia, akathisia, headache, insomnia, and anxiety. AL demonstrated robust efficacy in treatment of the subgroup of patients experiencing severe psychotic symptoms. Both doses (441mg and 882mg) were effective, with numerically greater improvement in symptoms and proportion of responders favoring the higher dose arm. Both doses had a side effect profile consistent with the known safety profile of aripiprazole.


Subunit structure of 27 S thyroid iodoprotein.
The dissociation of thyroid 27 S iodoprotein by sodium dodecyl sulfate (SDS) and by succinic anhydride was investigated by means of ultracentrifugation and polyacrylamide gel electrophoresis. The iodoprotein obtained from either a human or hog was dissociated into three kinds of subunits (S-19, S-17 and S-12) by SDS treatment. At increased concentrations of SDS, the S-12 subunit was predominant among the dissociation products. The succinylation of 27 S iodoprotein showed essentially the same dissociation pattern as in the case of SDS treatment. The dissociation products of the protein preparations of different animals were qualitatively the same as those of thyroglobulin of the respective animals, confirming the hypothesis that 27 S iodoprotein was composed of two molecules of thyroglobulin. However, the extent of dissociation of 27 S iodoprotein measured by S-12 formation showed higher resistancy of the protein to the dissociating agents than that of thyroglobulin. The contents of sialic acid and hexose as well as iodoamino acids of 27 S iodoprotein were found to be the same as, or not far from, those of thyroglobulin. The dissociability and chemical composition of 27 S iodoprotein was discussed with reference to the subunit structure of the protein.


Expression of CD44 is repressed in neuroblastoma cells.
We have used cDNA subtractive cloning to identify a group of human genes that are expressed in diverse differentiated derivatives of neural crest origin but not in neuroblastoma cell lines. One of these genes was identified as CD44, which encodes an integral membrane glycoprotein that serves as the principal receptor for hyaluronate and participates in specific cell-cell and cell-extracellular matrix interactions. The repression of CD44 expression in neuroblastoma cell lines might be relevant to their high metastatic potential. We have cloned full-length cDNAs corresponding to CD44 trancscripts and identified a novel splice variant of CD44 lacking 31 amino acids of the extracellular domain. As a first step toward analysis of CD44 downregulation in neuroblastoma cells, we have mapped the CD44 RNA initiation site and analyzed the structure of the upstream regulatory region. We constructed a series of plasmids containing different amounts of CD44 upstream regulatory region linked to the bacterial chloramphenicol acetyltransferase gene and then analyzed their ability to promote transcription in neuroblastoma and melanoma cells. We found that a DNA segment including about 150 bp of the CD44 upstream region and the 5' end of the gene itself was sufficient to induce substantial transcription of the chloramphenicol acetyltransferase gene in both neuroblastoma and melanoma cells. Several upstream cis-acting elements contribute to the downregulation of CD44 in neuroblastoma cells, the most prominent being a 120-bp DNA fragment located 450 bp upstream to the RNA initiation site. Our data suggest that multiple factors might be involved in downregulation of CD44 in neuroblastoma cells.


Malabsorption syndrome complicating tuberculous peritonitis.
A 22-year-old Nepali man presented with a 2-month history of fever, ill health, anorexia, loss of weight and diarrhoea. Apart from an ill-defined lower abdominal mass, physical examination was unremarkable. Investigations showed the picture of malabsorption syndrome with no evidence of structural gastro-intestinal tract involvement on barium meal, small bowel and large bowel enema, upper gastro-intestinal endoscopy, colonoscopy and mucous membrane biopsy. Laparoscopy showed typical features of tuberculous peritonitis. Liver biopsy showed tuberculous granulomatous hepatitis, and peritoneal biopsy showed caseating granulomata. The patient responded rapidly to antituberculosis chemotherapy.


Improvement and Retention of Arthroscopic Skills in Novice Subjects Using Fundamentals of Arthroscopic Surgery Training (FAST) Module.
Analysis of the Fundamentals of Arthroscopy Surgery Training (FAST) workstation regarding increased proficiency and retention of basic arthroscopy skills in novice subjects. First-year medical students from a single allopathic medical school performed weekly standardized FAST workstation modules for a consecutive 6 weeks. Primary outcomes evaluated were time to task completion and error rate on specific modules. Scores were analyzed using a one-way repeated measures analysis of variance design for overall trends in time and errors over the 6-week study. Psychomotor retention was analyzed after a 12-week and 24-week interlude. Across the initial 6-week study, the average time to complete all modules at the workstation decreased significantly (P < 0.001) with a mean reduction in the total workstation time of 21.9 minutes (s = 8.12 minutes). Weekly comparisons showed the most significant improvement from week 1 to week 2 for the total workstation time (P < 0.001). Results after a 12-week and 24-week interval of inactivity demonstrated no significant difference in the mean workstation time or errors when compared with the original 6-week study. The FAST workstation significantly improved the task performance of novice participants over a 6-week period with no significant deterioration in task performance after 12 and 24 weeks of inactivity.


Human pancreatic islets transfected to produce an inhibitor of TNF are protected against destruction by human leukocytes.
The objective of this study was to determine whether transfection of human islets with an adenovirus construct encoding an inhibitor of tumor necrosis factor (TNFi) was effective at limiting damage to beta cells induced by human peripheral blood leukocytes (huPBL). Human islets transfected with TNFi or control islets were transplanted under the kidney capsule of NOD-scid mice. After a 15-day engraftment period, half of the mice received injections of activated huPBL and half received buffer injections. Islet graft function was assessed by two different methods, both of which use a species-specific radioimmunoassay to determine human insulin. In some mice, insulin production following intraperitoneal glucose injection was determined in serum. In other mice, total graft insulin content was determined by acid ethanol extraction. Histochemical stains were performed on some kidneys at the termination of the experiment to evaluate graft presence, transgene expression, and huPBL infiltration. In huPBL injected mice, graft performance was maintained in mice whose grafts were transfected with TNFi but declined substantially in control groups with sham transfected or beta-galactosidase transfected islet grafts. Similar results were obtained using either glucose-stimulated insulin release or graft insulin content as a measure of graft survival. There was no significant difference in graft function between control groups receiving buffer injections, regardless of whether the islets had been transfected. Human leukocytes were found in all huPBL groups regardless of islet transfection status. We conclude that transfection of human islets with an adenovirus encoding TNFi protects beta cells from destruction induced by human leukocytes. The local production of TNFi does not prevent graft infiltration by leukocytes, only the destruction of grafts by the infiltrating leukocytes. These results raise the possibility that local expression of an inhibitor of the proinflammatory cytokine TNF-alpha may also prevent graft failure in clinical islet transplantation.


Adolescent substance-use assessment: methodological issues in the use of the ADAD (Adolescent Drug Abuse Diagnosis).
During the past twenty years, various instruments have been developed for the assessment of substance use in adolescents, mainly in the United States. However, few of them have been adapted to, and validated in, French-speaking populations. Consequently, although increasing alcohol and drug use among teenagers has become a major concern, the various health and social programs developed in response to this specific problem have received little attention with regard to follow-up and outcome assessment. A standardized multidimensional assessment instrument adapted for adolescents is needed to assess the individual needs of adolescents and assign them to the most appropriate treatment setting, to provide a single measurement within and across health and social systems, and to conduct treatment outcome evaluations. Moreover, having an available instrument makes it possible to develop longitudinal and trans-cultural research studies. For this reason, a French version of the Adolescent Drug Abuse Diagnosis (ADAD) was developed and validated at the University Child and Adolescent Psychiatric Clinic in Lausanne, Switzerland. This paper aims to discuss the methodological issues that we faced when using the ADAD instrument in a 4-year longitudinal study including adolescent substance users. Methodological aspects relating to the content and format of the instrument, the assessment administration and the statistical analyses are discussed.


Meningoencephalitis caused by human herpesvirus-6 in an immunocompetent adult patient: case report and review of the literature.
Human herpesvirus-6 (HHV-6) is the etiologic agent of roseola infantum, and has been implicated as a possible cause of encephalitis in pediatric and adult patients. A case of meningoencephalitis in an otherwise healthy, immunocompetent 59-year-old woman is described. The diagnosis of HHV-6 meningoencephalitis was confirmed by detecting viral DNA in cerebrospinal fluid collected in the acute stage of the disease by polymerase chain reaction. The patient was treated with acyclovir and recovered without any sequelae. The current knowledge of the pathophysiology, clinical course and outcome of HHV-6 meningoencephalitis in immunocompetent adult patients is also reviewed.


Myocyte TLR4 enhances enteric and systemic inflammation driving late murine endotoxic ileus.
Myocytes are nonhemopoietic in origin and functionally essential in generating gastrointestinal motility. In endotoxemia, a rapid-onset nonhemopoietic mechanism potently triggers early ileus in a Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88)-dependent manner. Moreover, synergistically with hemopoietic cells, nonhemopoietic cells escalate late ileus via an IL-6 receptor-dependent inflammation-driven pathway. We therefore specifically investigated the role of myocytes in TLR4-triggered inflammation and ileus. TLR4(+/+), TLR4(-/-), bmTLR4(+/+)/TLR4(-/-) chimera, SM22-Cre(-/-)TLR4(flox/flox), and selective myocyte TLR4-deficient (SM22-Cre(+/-)TLR4(flox/flox)) mice were injected intraperitoneally with purified lipopolysaccharide. SM22-driven Cre recombinase activity was selectively detected in cardiac, gastrointestinal, skeletal, and vascular myocytes, of small-sized vessels in a two-color fluorescent Cre reporter mouse. In contrast to nonhemopoietic TLR4 deficiency, deletion of myocyte TLR4 signaling prevented neither endotoxin-induced suppression of spontaneous jejunal contractility in vitro nor early ileus in vivo at 6 h. Circulating plasma colony-stimulating factor 3 was greatly elevated during endotoxemia, independent of myocyte TLR4 signaling or time. TLR4 activation of myocytes contributed significantly to an early enteric IL-6 mRNA induction and systemic IL-6 release, as well as to a late increase in circulating chemokine (C-X-C motif) ligand 1 (CXCL1) and IL-17. Consequently, inhibition of myocyte TLR4 signaling allowed functional recovery of motility by preventing inflammation-driven late ileus at 24 h. Direct TLR4 activation of myocytes is not responsible for nonhemopoietic-mediated early ileus. However, myocytes are proinflammatory cells that potently drive enteric and systemic inflammation, subsequently fueling late mediator-triggered ileus. Specifically, the myocyte TLR4-dependent inflammatory signature of elevated plasma IL-6, CXCL1, and IL-17 is strongly associated with late rodent ileus.


Fate of allelopathic substances in space--allelopathy of velvet bean plant and gravity.
Interactions between organisms and species have been long known. It has not been known that the interactive phenomena (allelopathy) may (or may not) differ in space from those on earth. We have studied the gravitational effects on allelopathy by exposing a plant-plant system to pseudo-microgravity, which was generated by a 3D-clinostat. We hypothesized that allelopathy would be modified under altered gravity. L-DOPA (L-3,4-dihydroxyphenylalanine) is known to be the major substance in the allelopathy of velvet bean, released from its root. It has been found that there have been some differences of the allelopathic action of velvet bean plant under pseudo-microgravity. Biosynthesis, release, transport and sensing mechanism associated with allelopathy might be affected by gravity.


The development of evidence-based supportive therapy guidelines for symptom management.
Systematic incorporation of toxicity assessment and grading during cancer treatment and subsequent provision of evidence-based patient interventions according to national standards for excellence are daunting tasks. To accomplish those goals, the authors' institution developed evidence-based supportive therapy guidelines for symptom management. This article describes how the guidelines provided concise, user-friendly standardization of toxicity grading and immediate clinical application of evidence-based care.


Thoracodorsal artery perforator flap: a versatile alternative for various soft tissue defects.
Thoracodorsal artery perforator (TDAP) flap is a relatively new member of the perforator flap family. The objective of this study is to describe the use of pedicled and free TDAP flaps for various soft tissue defects. Fifteen patients underwent soft tissue reconstruction using 16 TDAP flaps. Twelve pedicled flaps were used for axillary, breast, and shoulder regions. Four free flaps were used for cheek, popliteal, hand, and foot reconstruction. The flaps were harvested based on the perforators, which were preoperatively located at or close to a point 8 cm below the posterior axillary fold and 2 cm behind the lateral border of the latissimus dorsi muscle. Early, late, major, and minor complications were documented. In 13 of the 16 flaps, perforators from the thoracodorsal artery were found in the circle 3 cm in diameter, centered on the anatomic landmark. Three other perforators were found outside this circle. One flap loss was considered the only major complication. Minor complications occurred in 12.5% of flaps. Although the vascular anatomy can be variable, free and pedicled TDAP flap is a versatile option in soft tissue reconstruction.


Levels of Omega 3 fatty acids in Australian seafood.
The aim of this study was to determine the quantity of omega 3 (n-3) fatty acids in commonly consumed species of South Australian fish. Omega 3 fatty acids ranged from 17.7% to 53.7% of total fat with docosahexaenoic acid (DHA, 22:6n-3) as the major omega 3 fatty acid in all 26 species tested (range 9.5 % to 47.1% of total fat). The levels of total omega 6 (n-6) fatty acids ranged from 2.3% to 20.2% of total lipids, chiefly as arachidonic acid (AA, 20:4n-6). Fatty fish such as Gemfish, Atlantic Salmon and Swordfish were found to be good sources of omega-3 fatty acid (1360, 2252 and 2571 mg/100g fish respectively), while low fat fish such as Ling, Deep Sea Bream (Blue Warhou) and Blue Grenadier (0.5, 0.7 and 0.7% fat) had low levels of omega 3 fatty acid (222, 257 and 247 mg/100g). Because most white table fish consumed by Australians are so low in fat they are actually a limited source of omega 3 fats. The amount of fish required to be consumed to provide 1 g of omega 3 fatty acid per day ranged from 40 to 450 g.


Relationship of pulmonary function to radiographic interstitial fibrosis in 2,611 long-term asbestos insulators. An assessment of the International Labour Office profusion score.
Radiographic evidence of interstitial fibrosis (IF) secondary to asbestos inhalation (using the International Labour Office [ILO] profusion of small irregular opacities) was compared with FVC as an independent indicator of IF. In addition, spirometric indices of airflow (FEV1/FVC and FET25-75%) were correlated with the radiographic profusion score. A study of 2,611 long-term insulators was well designed for these analyses since all subjects were from the same trade, there were sufficient (n = 515) nonsmokers to assess the effects of asbestos exposure in the absence of smoking, most (60%, n = 1,557) of the workers had parenchymal abnormalities (scores greater than or equal to 1/0), and there was a greater prevalence of high scores than in other published series (347 workers or 13.3% had scores greater than or equal to 2/1). Looking at all subjects, the FVC decreased as profusion score increased. The FVC was abnormal (88.0% of predicted) even when the profusion score was clearly normal (0/0). The FVC was lower at any score in smokers and in workers with pleural thickening (more so with diffuse thickening). There was, however, no difference in FVC between intermediate scores 0/1 versus 1/0 and 1/2 versus 2/1. Airflow increased with greater profusion, tending to overcome a decrease seen at lesser profusion scores. These results provide a greater understanding of the relationships among profusion scores, smoking, pleural diseases, and pulmonary function.


Effects of a Long-Term Physical Activity Program on Activity Patterns in Older Adults.
To examine the effect of a long-term structured physical activity (PA) intervention on accelerometer-derived metrics of activity pattern changes in mobility-impaired older adults. Participants were randomized to either a PA or health education (HE) program. The PA intervention included a walking regimen with strength, flexibility, and balance training. The HE program featured health-related discussions and a brief upper body stretching routine. Participants (n = 1341) wore a hip-worn accelerometer for ≥10 h·d for ≥3 d at baseline and again at 6, 12, and 24 months postrandomization. Total PA (TPA)-defined as movements registering 100+ counts per minute-was segmented into the following intensities: low-light PA (LLPA; 100-759 counts per minute), high light PA (HLPA; 760-1040 counts per minute), low moderate PA (LMPA; 1041-2019 counts per minute), and high moderate and greater PA (HMPA; 2020+ counts per minute). Patterns of activity were characterized as bouts (defined as the consecutive minutes within an intensity). Across groups, TPA decreased an average of 74 min·wk annually. The PA intervention attenuated this effect (PA = -68 vs HE: -112 min·wk, P = 0.002). This attenuation shifted TPA composition by increasing time in LLPA (10+ bouts increased 6 min·wk), HLPA (1+, 2+, 5+, and 10+ bouts increased 6, 3, 2, and 1 min·wk, respectively), LMPA (1+, 2+, 5+, and 10+ bouts increased: 19, 17,16, and 8 min·wk, respectively), and HMPA (1+, 2+, 5+, and 10+ bouts increased 23, 21, 17, and 14 min·wk, respectively). The PA intervention increased PA by shifting the composition of activity toward higher-intensity activity in longer-duration bouts. However, a long-term structured PA intervention did not completely eliminate overall declines in total daily activity experienced by mobility-impaired older adults.


Magnesium: does a mineral prevent gallstones?
Gallstone-related disorders are common and costly, but preventive measures are largely unexplored. Lifestyle risk factors include physical activity, obesity/overweight, and diet. Increasing consumption of magnesium appears to decrease the risk of symptomatic gallstones in men, although the underlying mechanisms remain unclear. Understanding the role of a healthy diet in gallstone-related diseases, including a diet high in magnesium, may lead to new preventive measures.


Randomized trial on the physiologic impact of NOTES.
Our previous work revealed significantly less acidosis in swine undergoing natural orifice translumenal endoscopic surgery (NOTES) using endoscopic air insufflation than swine undergoing standard laparoscopy. We wanted to evaluate the differential effects of CO2 versus intra-abdominal pressure as source for this finding. In addition, we investigated the endocrine stress response between swine undergoing NOTES peritoneoscopy with CO2 insufflation and animals undergoing standard diagnostic laparoscopy with CO2. Twenty-eight (28) female 50-kg domestic pigs were randomly assigned to one of four groups using a permuted block randomization table: Group 1: NOTES using CO2 insufflation, Group 2: NOTES using air insufflation, Group 3: laparoscopy max pressure 12 mmHg and Group 4: laparoscopy with max pressure 7 mmHg. Invasive monitoring lines were placed. Pneumoperitoneum was established by the respective method and maintained for 90 min, visualizing liver, spleen and colon. Arterial blood gas was obtained at baseline and four additional time points. Serum TNF-α for POD (postoperative day) 1 and cumulative urine adrenaline for the procedure were determined by ELISA. ANOVA and t test were used for statistical comparison. The study was Institutional Animal Care and Use Committees approved. All experiments were completed as outlined. Blood pH showed a significant difference between groups. Serum TNF-α revealed higher levels for NOTES CO2 on POD 1 than standard laparoscopy (p = 0.03). NOTES animals with CO2 insufflation initially experienced similar pH compared to standard laparoscopy but recovered to levels seen in low-pressure laparoscopy and NOTES with air. NOTES with CO2 appears to elicit a stronger stress response in this study than standard or low-pressure laparoscopy or NOTES with air.


Protein micelles from lipoxygenase 3.
Heat-induced conformational changes in lipoxygenase 3 were characterized by differential scanning calorimetry. The positions of the observed transitions were sensitive to the composition of the buffer. In particular, lipoxygenase 3 heated in carbonate buffer at pH 8.0 formed large soluble aggregates. Variable-temperature circular dichroism revealed that the formation of the aggregates was not accompanied by the unfolding of the C-terminal domain, which is composed primarily of alpha-helix. The aggregates were investigated using size exclusion chromatography, native polyacrylamide gel electrophoresis, dynamic light scattering, and electron microscopy. The data were consistent with the formation of roughly spherical particles with an average hydrodynamic radius of 26 nm and an approximate composite molecular weight of 10,000,000 Da. To account for the formation of soluble aggregates from lipoxygenase 3, we propose that hydrophobic amino acid residues are exposed by unfolding of the N-terminal beta-barrel domain of the protein resulting in the formation of protein micelles with a hydrophilic surface composed of the C-terminal domains.


Physiological and transcriptional analyses reveal formation of memory under recurring drought stresses in seedlings of cotton (Gossypium hirsutum).
Plants are frequently subjected to a range of environmental stresses, including drought, salinity, cold, pathogens, and herbivore attacks. To survive in such conditions, plants have evolved a novel adaptive mechanism known as 'stress memory'. The formation of stress memories necessitates coordinated responses at the cellular, genetic/genomic, and epigenetic levels, involving altered physiological responses, gene activation, hyper-induction and chromatin modification. Cotton (Gossypium spp.) is an important economic crop with numerous applications and high economic value. In this study, we establish G. hirsutum drought memory following cycles of mild drought and re-watering treatments and analyzed memory gene expression patterns. Our findings reveal the physiological, biochemical, and molecular mechanisms underlying drought stress memory formation in G. hirsutum. Specifically, H3K4me3, a histone modification, plays a crucial role in regulating [+ /+ ] transcriptional memory. Moreover, we investigated the intergenerational inheritance of drought stress memory in G. hirsutum. Collectively, our data provides theoretical guidance for cotton breeding.


Murine hematopoietic stem cells and multipotent progenitors express truncated intracellular form of c-kit receptor.
The c-kit receptor plays a vital role in self-renewal and differentiation of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs). We have discovered that besides c-kit, the murine multipotent HSC/MPP-like cell line EML expresses the transcript and protein for a truncated intracellular form of c-kit receptor, called tr-kit. Notably, the tr-kit transcript and protein levels were down-regulated during cytokine-induced differentiation of the HSC/MPP-like cell line EML into myeloerythroid lineages. These findings prompted us to analyze tr-kit expression in purified murine fetal liver and bone marrow cell populations containing long-term repopulating (LTR) HSCs, short-term repopulating (STR) HSCs, MPPs, lineage-committed progenitors, and immature blood cells. Remarkably, these studies have revealed that in contrast to more widespread expression of c-kit, tr-kit is transcribed solely in cell populations enriched for LTR-HSCs, STR-HSCs, and MPPs. On the other hand, cell populations in which HSCs and MPPs are either present at a much lower frequency or are absent altogether, cells representing more advanced stages of differentiation into lymphoid and myeloid lineages do not express tr-kit. The observation that tr-kit is co-expressed with c-kit only in more primitive HSC- and MPP-enriched cell populations raises an exciting possibility that tr-kit functions either as a new component of the stem cell factor (SCF)/c-kit pathway or is involved in a novel signaling pathway, present exclusively in HSC and MPPs. Taken together, these findings necessitate functional characterization of tr-kit and analysis of its potential role in the self-renewal, proliferation, and/or differentiation of HSC and multipotent progenitors.


Treatment with AICAR inhibits blastocyst development, trophectoderm differentiation and tight junction formation and function in mice.
What is the impact of adenosine monophosphate-activated protein kinase (AMPK) activation on blastocyst formation, gene expression, and tight junction formation and function? AMPK activity must be tightly controlled for normal preimplantation development and blastocyst formation to occur. AMPK isoforms are detectable in oocytes, cumulus cells and preimplantation embryos. Cultured embryos are subject to many stresses that can activate AMPK. Two primary experiments were carried out to determine the effect of AICAR treatment on embryo development and maintenance of the blastocoel cavity. Embryos were recovered from superovulated mice. First, 2-cell embryos were treated with a concentration series (0-2000 μM) of AICAR for 48 h until blastocyst formation would normally occur. In the second experiment, expanded mouse blastocysts were treated for 9 h with 1000 μM AICAR. Outcomes measured included development to the blastocyst stage, cell number, blastocyst volume, AMPK phosphorylation, Cdx2 and blastocyst formation gene family expression (mRNAs and protein measured using quantitative RT-PCR, immunoblotting, immunofluorescence), tight junction function (FITC dextran dye uptake assay), and blastocyst ATP levels. The reversibility of AICAR treatment was assessed using Compound C (CC), a well-known inhibitor of AMPK, alone or in combination with AICAR. Prolonged treatment with AICAR from the 2-cell stage onward decreases blastocyst formation, reduces total cell number, embryo diameter, leads to loss of trophectoderm cell contacts and membrane zona occludens-1 staining, and increased nuclear condensation. Treatment with CC alone inhibited blastocyst development only at concentrations that are higher than normally used. AICAR treated embryos displayed altered mRNA and protein levels of blastocyst formation genes. Treatment of blastocysts with AICAR for 9 h induced blastocyst collapse, altered blastocyst formation gene expression, increased tight junction permeability and decreased CDX2. Treated blastocysts displayed three phenotypes: those that were unaffected by treatment, those in which treatment was reversible, and those in which effects were irreversible. Not applicable. Our study investigates the effects of AICAR treatment on early development. While AICAR does increase AMPK activity and this is demonstrated in our study, AICAR is not a natural regulator of AMPK activity and some outcomes may result from off target non-AMPK AICAR regulated events. To support our results, blastocyst developmental outcomes were confirmed with two other well-known small molecule activators of AMPK, metformin and phenformin. Metformin, an AMPK activator, is widely used to treat type II diabetes and polycystic ovarian disorder (PCOS). Our results indicate that early embryonic AMPK levels must be tightly regulated to ensure normal preimplantation development. Thus, use of metformin should be carefully considered during preimplantation and early post-embryo transfer phases of fertility treatment cycles. Canadian Institutes of Health Research (CIHR) operating funds. There are no competing interests.


Further Phenotypic Delineation of Partial Trisomy 17q and Partial Monosomy 20q due to Rare t(17;20).
Copy number variations in subtelomeric regions of chromosomes 17 and 20 are associated with intellectual disability and various systemic manifestations. Microarray analysis allows identification of submicroscopic chromosomal abnormalities and is applicable to elucidate the etiology of cognitive impairment in approximately one-fifth of the cases. In the present study, we report on 3 male children from 2 sisters, who suffered from intellectual disability, facial dysmorphism, and epilepsy. Despite the initial suggestion of an X-linked inheritance, the condition was associated with 17q25.3 duplication and concomitant 20q13.33 deletion, as detected by microarray analysis. Coexistence of a deletion and a duplication suggests unbalanced segregation of a parental balanced translocation. Further investigations revealed maternal balanced translocations, which resulted in copy number aberrations in the children following unbalanced segregations. The work-up underlined the importance of genomic screening using microarrays as the first-tier diagnostic tool in intellectual disability, despite an apparent X-linked segregation in the pedigree.


Two Roads Diverge: Treatment Choice in Coexisting Severe Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria.
Aplastic anemia (AA) is a bone marrow failure syndrome of pancytopenia due to impaired hematopoiesis. It is strongly associated with paroxysmal nocturnal hemoglobinuria (PNH). Each condition can cause the other, or occur simultaneously. There are no guidelines for treating concomitant AA and PNH; immunosuppressive therapy (IST) or hematopoietic stem cell therapy (HSCT) is first-line for the former, and eculizumab is first-line for the latter. New studies suggest that treating AA/PNH together versus sequentially should depend on AA severity. We report the case of a previously healthy male (31-year-old, Nigerian immigrant) who developed jaundice, scleral icterus, easy fatigability, and epistaxis. He was diagnosed with AA on bone marrow biopsy and with PNH on flow cytometry. He initially underwent chemotherapy due to increased infection risk with eculizumab in a neutropenic patient; however, he showed minimal response and thus began eculizumab pending allogeneic stem cell transplant. There are no guidelines for treating patients with both AA and PNH, and clinical decision making is generally individualized based on disease severity. Only one prior publication reported simultaneous treatment with eculizumab and chemotherapy, due to stated concern for pancytopenia, especially neutropenia, being the most immediate cause of morbidity/mortality. This demonstrates the individualized decisions that must be made when treating simultaneous PNH and AA, and the importance of PNH/severe AA patients as a separate subpopulation.


Chemical Crosslinking of 6FDA-ODA and 6FDA-ODA:DABA for Improved CO₂/CH₄ Separation.
Chemical grafting or crosslinking of polyimide chains are known to be feasible approaches to increase polymer gas-pair selectivity and specific gas permeance. Different co-polyimides; 6FDA-ODA and 6FDA-ODA:DABA were synthesized using a two-step condensation method. Six different cross-linkers were used: (i) m-xylylene diamine; (ii) n-ethylamine; and (iii) n-butylamine, by reacting with 6FDA-ODA's imide groups in a solid state crosslinking; while (iv) ethylene glycol monosalicylate (EGmSal); (v) ethylene glycol anhydrous (EGAn); and (vi) thermally labile iron (III) acetylacetonate (FeAc), by reacting with DABA carboxyl groups in 6FDA-ODA:DABA. The gas separation performances were evaluated by feeding an equimolar CO₂ and CH₄ binary mixture, at a constant feed pressure of 5 bar, at 25 °C. Fractional free volume (FFV) was calculated using Bondi's contribution method by considering the membrane solid density property, measured by pycnometer. Other characterization techniques: thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) were performed accordingly. Depending on the type of amine, the CO₂/CH₄ selectivity of 6FDA-ODA increased between 25 to 100% at the expense of CO₂ permeance. We observed the similar trend for 6FDA-ODA:DABA EGmSal-crosslinked with 143% selectivity enhancement. FeAc-crosslinked membranes showed an increment in both selectivity and CO₂ permeability by 126% and 29% respectively. Interestingly, FeAc acted as both cross-linker which reduces chain mobility; consequently improving the selectivity and as micro-pore former; thus increases the gas permeability. The separation stability was further evaluated using 25⁻75% CO₂ in the feed with CH₄ as the remaining, between 2 and 8 bar at 25 °C. We also observed no CO₂-induced plasticization to the measured pressure with high CO₂ content (max. 75%).


Non-moving Hadamard matrix diffusers for speckle reduction in laser pico-projectors.
Personal electronic devices such as cell phones and tablets continue to decrease in size while the number of features and add-ons keep increasing. One particular feature of great interest is an integrated projector system. Laser pico-projectors have been considered, but the technology has not been developed enough to warrant integration. With new advancements in diode technology and MEMS devices, laser-based projection is currently being advanced for pico-projectors. A primary problem encountered when using a pico-projector is coherent interference known as speckle. Laser speckle can lead to eye irritation and headaches after prolonged viewing. Diffractive optical elements known as diffusers have been examined as a means to lower speckle contrast. This paper presents a binary diffuser known as a Hadamard matrix diffuser. Using two static in-line Hadamard diffusers eliminates the need for rotation or vibration of the diffuser for temporal averaging. Two Hadamard diffusers were fabricated and contrast values measured showing good agreement with theory and simulated values.


Analyses of protein sequences using inter-residue average distance statistics to study folding processes and the significance of their partial sequences.
One of the goals of molecular bioinformatics is decoding amino acid sequences to extract information on the principles of protein folding. However, this is difficult to perform with standard bioinformatics techniques such as multiple sequence alignment and so on. Thus, we propose a technique based on inter-residue average distance statistics to make predictions regarding the protein folding mechanisms of amino acid sequences. Our method involves constructing a kind of predicted contact map called an Average Distance Map (ADM) based on average distance statistics to pinpoint regions of possible folding nuclei for proteins. Only information on the amino acid sequence of a given protein is required for the present method. In this article, we summarize the results of studies using our method to analyze how specific protein sequences affect folding properties. In particular, we present studies on proteins in the phage lysozyme, such as the globin, fatty acid binding protein-like, and the cupredoxin-like fold families. In the present review, we characterize the 3D architectures of these proteins through the properties of the protein ADMs. Furthermore, we combine the information on the conserved residues within the regions predicted by the ADMs with our results obtained so far. Such information may help identify the folding characteristics of each protein. We discuss this possibility in the present review.


A Tunable Freeform-Segmented Reflector in a Microfluidic System for Conventional and Surface-Enhanced Raman Spectroscopy.
We present a freeform-segmented reflector-based microfluidic system for conventional Raman and Surface-Enhanced Raman Scattering (SERS) analysis. The segmented reflector is directly designed by a numerical approach. The polymer-based Raman system strongly suppresses the undesirable background because it enables confocal detection of Raman scattering through the combination of a freeform reflector and a microfluidic chip. We perform systematic simulations using non-sequential ray tracing with the Henyey-Greenstein model to assess the Raman scattering behavior of the substance under test. We fabricate the freeform reflector and the microfluidic chip by means of ultra-precision diamond turning and laser cutting respectively. We demonstrate the confocal behavior by measuring the Raman spectrum of ethanol. Besides, we calibrate the setup by performing Raman measurements on urea and potassium nitrate solutions with different concentrations. The detection limit of our microfluidic system is approximately 20 mM according to the experiment. Finally, we implement a SERS microfluidic chip and discriminate 100 µM urea and potassium nitrate solutions.


Glioblastoma multiforme.
Optimal management of newly diagnosed glioblastoma multiforme includes maximal surgical resection, followed by 60 Gy of external beam radiation plus concomitant daily temozolomide and at least six additional monthly cycles of maintenance temozolomide. Several large phase 3 trials are now ongoing to determine whether agents added to this regimen may confer further survival advantage. At the time of disease recurrence, bevacizumab is the most commonly used agent. Whenever feasible, patients should be encouraged to participate in clinical trials, which are currently focused on antiangiogenic and targeted therapies.


Bioengineering of surface GD3 ganglioside for immunotargeting human melanoma cells.
N-Propionyl, N-butyryl (N-Bu), and N-benzoyl mannosamine, as precursors of sialic acid biosynthesis, were incubated with human melanoma SK-MEL-28 cells and resulted in the replacement of N-acetyl groups on the cell surface sialic acid residues, including those associated with GD3. Meanwhile, vaccines containing GD3 and modified GD3 tetrasaccharide-keyhole limpet hemocyanin conjugates were synthesized, and BALB/c mice were immunized with them together with monophosphoryl lipid A adjuvant. The GD3Bu-keyhole limpet hemocyanin conjugate raised the highest IgG titers without any cross-reactivity to unmodified GD3. Expression of GD3Bu epitopes on the surface of SK-MEL-28 cells was confirmed in vitro and in vivo by the binding of a polyclonal antiserum and monoclonal antibody (mAb) 2A, both of which specifically recognize GD3Bu, and by mass spectroscopic analysis of glycolipids extracted from cells. Following expression of GD3Bu on the surface of SK-MEL-28 cells, the cells could be lysed by mAb 2A and GD3Bu antiserum in the presence of complement. Although less effective in the control of existing large size tumors ( approximately 10 mm inner diameter) on BALB/c nu/nu mice, mAb 2A in combination with ManNBu effectively protected mice from SK-MEL-28 tumor grafting. This approach may provide a method to augment the immunogenicity of sialylated human antigens and to avoid generating an autoimmune response to them at same time.


Comparison of the applicability of four odontological methods for age estimation of the 14 years legal threshold in a sample of Italian adolescents.
The 14-years age threshold is especially important in Italy for criminal, civil and administrative laws. Several methods relying on dental calcification of the teeth, up to the second molar, are used for the evaluation of age in childhood. The objective of the research was to compare the inter-rater agreement and accuracy of four common methods for the dental age estimation - Demirjian (D), Willems (W), Cameriere (C) and Haavikko (H) - in a sample of Italian adolescents between 11 and 16 years. The sensitivity and specificity, and the different level of probability, according to the peculiarities of Italian criminal and civil law, were compared for the methods examined, considering the threshold of 14 years. The sample was composed of 501 digital OPGs of Italian children (257 females and 244 males), aged from 11 years and 0 days to 15 years and 364 days. The maturation stage of the teeth was evaluated according to D, W, H and C methods by three independent examiners. Mixed statistical models were applied to compare the accuracy and the errors of each method. The inter-rater agreement was high for the four methods and the intraclass correlation coefficients were all ≥ 0.81. Methods H and C showed a general tendency to underestimate the age in the considered sample while the methods D and W tended to overestimate the child's age. In females, D and W were more accurate than C, which is more accurate than H. In the males, W is the most accurate method even though it over-estimated age. Considering the 14-years threshold, the sensitivity of D and W methods is quite high (range 0.80; 0.95) and specificity is low (range 0.61; 0.86). The principal findings of the research are: the W and D methods are much more accurate than C and H, but they tend to overestimate the age. The C method largely underestimates the age (by ~1 year) for both genders and for all operators. H is unsuitable for dental age estimation in the Italian population, while W and D yielded high sensitivity but low specificity, thus producing high rates of false positive results. The choice of method to estimate if an Italian child has reached the 14-years legal threshold should mainly be chosen according to the different legal milieu (if civil or criminal) and the gender of the examined individual. The age assessment in criminal case must be prudently managed.


[Gaucher's disease and pregnancy].
The authors describe a female patient with a chronic pattern of Gaucher's disease which remained unrecognized for a long time. Pregnancy was noted to affect the disease progress and development of liver cellular failure as well as the hemorrhagic syndrome. Splenectomy gave rise to a stable disease remission followed by normal pregnancy and delivery.


Anatomical factors determining surgical decision-making in patients with transposition of the great arteries with left ventricular outflow tract obstruction.
Transposition of the great arteries (TGA) and left ventricular outflow tract obstruction (LVOTO) with or without ventricular septal defect have multiple surgical treatment options. We sought to identify pre- and intraoperative factors that determine the timing of repair, procedure type and subsequent LVOT outcome. Twenty-eight (8.2% of all TGA) patients with TGA with LVOTO (double outlet ventricle, n = 5, TGA/intact septum, n = 1) between 2000 and 2012 were reviewed. Anatomical factors were identified by prerepair echocardiography. LVOTO complexity was characterized by the degree of obstruction (0 = none, 0.33 = mild, 0.66 moderate and 1 = severe) at various levels: pulmonary valve (PV) dysplasia/hypoplasia, posterior deviation of the infundibular septum, fibromuscular ridge, tissue tag and abnormal chordal attachment. Summation of the obstruction score, at each level, yielded the LVOT complexity score. The descriptive analysis of intraoperative decision-making at late repair was performed. early arterial switch operation (ASO) + LVOT resection (n = 9, 32%), late ASO + LVOT resection (n = 3, 10%), Nikaidoh (n = 8, 29%), Rastelli (n = 6, 21%), single-ventricle palliation (n = 2, 7%). The primary LVOT obstruction mechanism was posterior deviation of the infundibular septum (n = 16, 57%) and PV dysplasia (n = 6, 21%). The early ASO group had a lower PV complexity score (0.42 ± 0.22 vs 0.96 ± 0.55, P = 0.007), tissue tag score (0.03 ± 0.15 vs 0.26 ± 0.34, P = 0.018) and LVOT complexity score (2.11 ± 0.86 vs 3.2 ± 0.96, P = 0.006). The LVOT complexity score in the Nikaidoh group was higher than in the late ASO group (P = 0.019). Of 16 candidates for the Nikaidoh procedure, 6 patients underwent a Rastelli operation due to coronary artery patterns (single coronary, n = 3, 1RL-2Cx, n = 2 or an abnormal left anterior descending coronary artery course, n = 1). Two patients underwent single-ventricle palliation due to the interference of essential chordae. All patients survived the operation. The 3-year survival was 96%. One patient who underwent late ASO required re-LVOT resection. A newly developed scoring system, the LVOT complexity score, helped to quantify the LVOT complexity and was correlated with our choice of the surgical procedure of TGA with LVOTO. The current strategy achieved reasonable survival and LVOT outcome with three quarters of the patients having an anatomically aligned LVOT. The coronary anatomy pattern was the primary determinant in the decision-making between the Nikaidoh procedure and the Rastelli operation.


Effects of LDL apheresis on blood rheology in two patients with homozygous familial hypercholesterolaemia.
Changes in haemorheological and lipid variables were investigated in 2 patients with homozygous familial hypercholesterolaemia (FH) treated with low-density lipoprotein (LDL) apheresis using dextran sulphate adsorbent. The immediate effect of LDL apheresis was a fall in plasma fibrinogen by 50%, total and LDL cholesterol by 60%, plasma viscosity by 12% and whole blood viscosity by 17%. Before the 12th treatment session, plasma fibrinogen concentration remained reduced by 22%, whole blood viscosity by 17% and the plasma viscosity by 11% compared with the initial values. Total and LDL cholesterol in plasma also remained reduced by about 50%. We conclude that LDL apheresis, using dextran sulphate adsorbent, improves blood rheology. The decrease in plasma fibrinogen concentrations, plasma viscosity and LDL cholesterol might be factors contributing to the improved haemorheological properties.


Climate warming and agricultural stressors interact to determine stream periphyton community composition.
Lack of knowledge about how the various drivers of global climate change will interact with multiple stressors already affecting ecosystems is the basis for great uncertainty in projections of future biological change. Despite concerns about the impacts of changes in land use, eutrophication and climate warming in running waters, the interactive effects of these stressors on stream periphyton are largely unknown. We manipulated nutrients (simulating agricultural runoff), deposited fine sediment (simulating agricultural erosion) (two levels each) and water temperature (eight levels, 0-6 °C above ambient) simultaneously in 128 streamside mesocosms. Our aim was to determine the individual and combined effects of the three stressors on the algal and bacterial constituents of the periphyton. All three stressors had pervasive individual effects, but in combination frequently produced synergisms at the population level and antagonisms at the community level. Depending on sediment and nutrient conditions, the effect of raised temperature frequently produced contrasting response patterns, with stronger or opposing effects when one or both stressors were augmented. Thus, warming tended to interact negatively with nutrients or sediment by weakening or reversing positive temperature effects or strengthening negative ones. Five classes of algal growth morphology were all affected in complex ways by raised temperature, suggesting that these measures may prove unreliable in biomonitoring programs in a warming climate. The evenness and diversity of the most abundant bacterial taxa increased with temperature at ambient but not with enriched nutrient levels, indicating that warming coupled with nutrient limitation may lead to a more evenly distributed bacterial community as temperatures rise. Freshwater management decisions that seek to avoid or mitigate the negative effects of agricultural land use on stream periphyton should be informed by knowledge of the interactive effects of multiple stressors in a warming climate.


[The effect of antidepressants on brain volume].
In this review, we summarise all studies of patients with depression, who have been examined by MRI before and after treatment with antidepressants. None of the studies showed any signs of damage to the brain tissue after treatment. On the contrary, most studies showed increases in hippocampal volume and prefrontal cortices in parallel with response or remission after treatment. As depression in several meta-analyses has been shown to double the risk for dementia, this could have important implications for preventive measures, because, for instance, hippocampal atrophy is seen in both diseases.


Designed peptides for biomineral polymorph recognition: a case study for calcium carbonate.
With their unique ability for substrate recognition and their sequence-specific self-assembly properties, peptides play an important role in controlling the mineralization of inorganic materials in natural systems and in controlling the assembly of soft materials into complex structures required for biological functions. Here we report the use of an engineered heptapeptide that can differentiate between the crystalline anhydrous polymorphs of calcium carbonate. This peptide contains the positively charged amino acid arginine as well as proline rather than the prototypical negatively charged aspartate or glutamate units. Its affinity to vaterite compared to aragonite was demonstrated by fluorescence microscopy using biotinylated peptides. Crystallization experiments in the presence of the vaterite-affine peptide afforded only vaterite, whereas a mutant peptide, where a proline residue was replaced by glycine, exclusively leads to the formation of calcite.


Integration of SecA protein into the Escherichia coli inner membrane is regulated by its amino-terminal ATP-binding domain.
SecA protein, the ATPase promoting translocation of proteins across the Escherichia coil inner membrane, contains two ATP-binding domains that differ greatly in their affinity for bound nucleotide. In order to define more precisely the location of the high-affinity nucleotide-binding site, oligonucleotide-directed mutagenesis was used to introduce cysteine residues into the SecA sequence, and a cysteine-specific cleavage reagent was employed to generate defined peptides of SecA protein after photocross-linking with [alpha-(32)P]-ATP. This analysis revealed that the nucleotide was cross-linked between amino acid residues 75 and 97 of SecA protein. The biochemical function of the high affinity ATP-binding domain was explored by subcellular fractionation studies which demonstrated that SecA proteins defective in this region were found almost exclusively in their integral membrane form, while SecA proteins with defects in the low-affinity ATP-domain showed a normal distribution of cytosolic, peripheral and integral membrane forms. Interestingly, the SecA51(Ts) protein that has a Leu to Pro substitution at amino acid residue 43 bound ATP with high affinity, but its fractionation pattern and translocation ATPase activity were similar to those of proteins with defects in the high-affinity ATP-binding site. These results delimit more precisely the high-affinity ATP-binding domain of SecA, indicate the importance of the early amino-terminal region of SecA protein in the functioning of this domain, and demonstrate the role of this domain in regulating penetration of SecA protein into the inner membrane. Our results lead to a simple model for the regulation of a cycle of SecA insertion into, and de-insertion from, the inner membrane by the activity of the high affinity ATP-binding domain.


A data-driven network model for the emerging COVID-19 epidemics in Wuhan, Toronto and Italy.
The ongoing Coronavirus Disease 2019 (COVID-19) pandemic threatens the health of humans and causes great economic losses. Predictive modeling and forecasting the epidemic trends are essential for developing countermeasures to mitigate this pandemic. We develop a network model, where each node represents an individual and the edges represent contacts between individuals where the infection can spread. The individuals are classified based on the number of contacts they have each day (their node degrees) and their infection status. The transmission network model was respectively fitted to the reported data for the COVID-19 epidemic in Wuhan (China), Toronto (Canada), and the Italian Republic using a Markov Chain Monte Carlo (MCMC) optimization algorithm. Our model fits all three regions well with narrow confidence intervals and could be adapted to simulate other megacities or regions. The model projections on the role of containment strategies can help inform public health authorities to plan control measures.


Clinical analysis of 51 cases of aortic dissection.
To evaluate the effects of different treatments on the prognosis of aortic dissection. Different treatment modalities including drug therapy, surgical resection and stent implantation were performed in 37, 9, and 5 cases of aortic dissection (AD) respectively, and the clinical outcome of the patients was observed during the follow-up study. The survival rate in drug therapy group was 70.3% (26) while death occurred in 11 cases (29.7%). Four (44.4%) of the nine cases were cured surgically, leaving a mortality of 55.6%. Stent implantation yielded cures in 4 cases, with death occurring in 1 case, and complications arose in none of the cases. Surgical resection is superior to drug therapy in the treatment of type A AD cases, while stent implantation should be the first choice for type B AD cases for causing less complications and injuries and resulting in high cure rate.


Hydrogen Behavior at Crystalline/Amorphous Interface of Transparent Oxide Semiconductor and Its Effects on Carrier Transport and Crystallization.
The role of disorder and particularly of the interfacial region between crystalline and amorphous phases of indium oxide in the formation of hydrogen defects with covalent (In-OH) or ionic (In-H-In) bonding are investigated using ab initio molecular dynamics and hybrid density-functional approaches. The results reveal that disorder stabilizes In-H-In defects even in the stoichiometric amorphous oxide and also promotes the formation of deep electron traps adjacent to In-OH defects. Furthermore, below-room-temperature fluctuations help switch interfacial In-H-In into In-OH, creating a new deep state in the process. This H-defect transformation limits not only the number of free carriers but also the grain size, as observed experimentally in heavily H-doped sputtered In2Ox. On the other hand, the presence of In-OH helps break O2 defects, abundant in the disordered indium oxide, and thus contributes to faster crystallization rates. The divergent electronic properties of the ionic vs covalent H defects─passivation of undercoordinated In atoms vs creation of new deep electron traps, respectively─and the different behavior of the two types of H defects during crystallization suggest that the resulting macroscopic properties of H-doped indium oxide are governed by the relative concentrations of the In-H-In and In-OH defects. The microscopic understanding of the H defect formation and properties developed in this work serves as a foundation for future research efforts to find ways to control H species during deposition.


What mechanisms can't do: explanatory frameworks and the function of the p53 gene in molecular oncology.
What has been called the new mechanistic philosophy conceives of mechanisms as the main providers of biological explanation. We draw on the characterization of the p53 gene in molecular oncology, to show that explaining a biological phenomenon (cancer, in our case) implies instead a dynamic interaction between the mechanistic level-rendered at the appropriate degree of ontological resolution-and far more general explanatory tools that perform a fundamental epistemic role in the provision of biological explanations. We call such tools "explanatory frameworks". They are called frameworks to stress their higher level of generality with respect to bare mechanisms; on the other hand, they are called explanatory because, as we show in this paper, their importance in explaining biological phenomena is not secondary with respect to mechanisms. We illustrate how explanatory frameworks establish selective and local criteria of causal relevance that drive the search for, characterisation and usage of biological mechanisms. Furthermore, we show that explanatory frameworks allow for changes of scientific perspective on the causal relevance of mechanisms going beyond the account provided by the new mechanistic philosophy.


Development and validation of a childhood self-efficacy for functional constipation questionnaire.
Children with functional constipation fear painful bowel movements leading to stool withholding behavior. Self-efficacy is the belief that an individual can accomplish a given goal. If children with constipation avoid defecation because they think that they are unable defecate comfortably, this low self-efficacy may prevent treatment success. The aim of the current study was to develop and validate a constipation specific self-efficacy scale. The self-efficacy for functional constipation questionnaire (SEFCQ) was developed by the authors and evaluated by 10 children and seven experts. Ninety-nine healthy children and 122 children with functional constipation completed the SEFCQ and three other questionnaires measuring related constructs. Minor changes were made in wording based on feedback from experts and children. Factor analysis showed two scales, a 7 item Action scale (Cronbach's α = 0.88) and a 7 item Emotion scale (Cronbach α = 0.86). The SEFCQ total scale correlated positively with general self-efficacy (r = .32, P < .001) and quality of life (r = .20; P < .01) and negatively with anxiety (r = -.15; P < .05). Scores on the SEFCQ were higher in children without functional constipation compared to those with functional constipation (53.33 + 3.38 vs 39.34 + 7.19, P < .001). We developed a constipation specific self-efficacy questionnaire with good initial internal reliability, excellent face validity and adequate content validity. A low self-efficacy for defecation, may make the child resist their physical urge to defecate and hence, the need for further studies to assess its effect on treatment outcomes.


Fusion protein of the paramyxovirus SV5: destabilizing and stabilizing mutants of fusion activation.
The fusion (F) protein of the paramyxovirus SV5 strain W3A causes syncytium formation without coexpression of the SV5 hemagglutinin-neuraminidase (HN) glycoprotein, whereas the F protein of the SV5 strain WR requires coexpression of HN for fusion activity. SV5 strains W3A and WR differ by three amino acid residues at positions 22, 443, and 516. The W3A F protein residues P22, S443, and V516 were changed to amino acids found in the WR F protein (L22, P443, and A516, respectively). Three single-mutants, three double-mutants, and the triple-mutant were constructed, expressed, and assayed for fusion using three different assays. Mutant P22L did not cause fusion under physiological conditions, but fusion was activated at elevated temperatures. Compared with the W3A F protein, mutant S443P enhanced the fusion kinetics with a faster rate and greater extent, and had a lower activation temperature. Mutant V516A had little effect on F protein-mediated fusion. The double-mutant P22L,S443P was capable of causing fusion, suggesting that the two mutations have opposing effects on fusion activation. The WR F protein requires coexpression of HN to cause fusion at 37 degrees C, and does not cause fusion at 37 degrees C when coexpressed with influenza virus hemagglutinin (HA); however, at elevated temperatures coexpression of WR F protein with HA resulted in fusion activation. In the crystal structure of the core trimer of the SV5 F protein (Baker, K. A., Dutch, R. E., Lamb, R.A., and Jardetzky, T. S. (1999). Mol. Cell 3, 309-319), S443 is the last residue (with interpretable electron density) in an extended chain region and the temperature factor for S443 is high, suggesting conformational flexibility at this point. Thus, the presence of prolines at residues 22 and 443 may destabilize the F protein and thereby decrease the energy required to trigger the presumptive conformational change to the fusion-active state.


Human calcitonin gene regulation by helix-loop-helix recognition sequences.
Human calcitonin (CT) gene transcription is regulated by proximal 5' flanking sequences which mediate cAMP-induced expression, and by a distal basal enhancer region. Using transient expression of CT-CAT constructs, we showed that the basal enhancer is active in a CT-producing small cell lung cancer cell line (DMS53) and the thyroid C cell derived tumor line, TT, but is inactive in non-CT-producing cell lines. In deletional and direct mutational analyses of the distal enhancer region, disruption of two elements resembling recognition sequences for the helix-loop-helix (HLH) family of transcriptional regulatory proteins resulted in a significant loss of basal transcriptional enhancer action. These results suggest that HLH recognition motifs may mediate a significant portion of constitutive CT gene transcriptional activity in these cells. Nuclear protein extracts from DMS53 cells formed specific binding complexes with oligonucleotides containing two of these candidate enhancer sequences. However, proteins capable of binding to these CT gene HLH consensus recognition sites were not restricted to CT-producing cells. We conclude that members of the HLH protein family, some expressed ubiquitously and some expressed or activated in a tissue-restricted fashion, may combine to enhance CT gene transcription in tumor cells of neuroendocrine derivation.


Support of the perioperative failing heart with preexisting ventricular dysfunction: currently available options.
Perioperative support of the patient with preexisting biventricular failure requires simultaneous optimal manipulation of heart rate and rhythm, loading conditions, and contractility. Patients with preexisting ventricular dysfunction will have alterations in beta-adrenergic receptors, resulting in decreased responsiveness to catecholamines. Even patients with previously normal ventricular function can develop ventricular dysfunction caused by reperfusion injury and other potentially damaging effects of extracorporeal circulation. The mainstay of therapeutic agents used to allow separation from cardiopulmonary bypass are catecholamines, which stimulate alpha- and beta-adrenergic receptors. Submaximal responses to beta 1-adrenergic stimulation can occur in the down-regulated heart. The phosphodiesterase inhibitors provide both inotropic support and vasodilatation, which improves both systolic and diastolic function and bypasses beta-adrenergic receptors. When administered in combination, catecholamine and cyclic-AMP-specific phosphodiesterase inhibitors can have additive effects to restore beta 1-adrenergic responsiveness. Combination therapy provides an important therapeutic option to facilitate separation from cardiopulmonary bypass. Pharmacologic intervention for right ventricular dysfunction focuses on reversal of pulmonary vasoconstriction with nitrates, beta 2-adrenergic agents, phosphodiesterase inhibitors and prostaglandin E1.


B7-H3 regulates migration and invasion in salivary gland adenoid cystic carcinoma via the JAK2/STAT3 signaling pathway.
B7 Homolog 3 (B7-H3), a newly identified member of the B7 family, is over-expressed in various human cancers and plays a vital role in tumor progression. To identify the expression pattern of B7-H3 in human salivary adenoid cystic carcinoma (AdCC) and its underlying mechanisms, we characterized B7-H3 expression in AdCC tissue microarrays using immunohistochemical staining, and analyzed potentially associated molecules. The results showed that B7-H3 was highly expressed in salivary AdCC, compared with normal salivary glands. Statistical analyses of immunohistochemical staining showed that B7-H3 was closely correlated with Slug and p-STAT3. Functional studies showed that knockdown of B7-H3 in AdCC cell lines using RNA interference did not influence cell growth and apoptosis, but decreased migration and invasion in vitro. Further mechanism studies suggested that B7-H3 influenced the migration and invasion of AdCC cells by regulating the epithelial-mesenchymal transition via JAK2/STAT3 pathway components. Collectively, these findings suggested that B7-H3 may be a potential therapeutic target for AdCC.


Pj variant, a new hybrid MNSs glycoprotein of the human red-cell membrane.
An unusual glycoprotein variant (Pj) was found inherited through a caucasian family exhibiting atypical N and Nvg blood-group reactivities. Pj erythrocytes are blood-group-MS homozygous and have a normal sialic acid content. On sodium dodecyl sulphate/polyacrylamide-gel electrophoresis the variant contains a new component Pj of 24kDa apparent molecular mass in the monomeric state which is sharply stained by periodic acid/Schiff reagent. Both blood-group-MN (alpha) and -Ss (delta) glycoproteins were present. Homodimers (Pj2) as well as heterodimers with MN-glycoprotein (alpha Pj) and the Ss-glycoprotein (delta Pj) were also identified. The new sialoglycoprotein Pj is trypsin- and chymotrypsin-resistant in situ and carries N- and Nvg- but not M- and S-reactivities. The Pj component is labelled by lactoperoxidase-catalysed radioiodination. A 3H label is also easily introduced into the sialic acid or the galactose and galactosamine of the Pj glycoprotein. It is proposed that the Pj is a hybrid glycoprotein containing the N-terminal end of delta-glycoprotein and the C-terminal end of the alpha-glycoprotein. This proposal is supported by the finding that Pj carries a leucine residue at its N-terminus and is not immunoprecipitated by a monoclonal mouse antibody (R18) reacting specifically with the external domain of glycoprotein alpha. The red cells from the proposita Pj were found positive for a very low frequency MN antigen named Sta.


Lesion-Specific Factors Contributing to Inhospital Costs in Adults With Congenital Heart Disease.
The population of adults with congenital heart disease (ACHD) in the United States is growing rapidly with concomitant increases in care costs. We sought to define the variables having the greatest influence on annual cost of inpatient care in patients with ACHD in the United States. To do so, we conducted a retrospective analysis of admissions in patients >18 years old with a 3-digit International Classification of Disease, Ninth Revision, code of 745 to 747 from the State Inpatient Databases of Arkansas (2008 to 2010), California (2003 to 2012), Florida (2005 to 2012), Hawaii (2006 to 2010), Nebraska (2003 to 2011), and New York (2005 to 2012). We selected variables we believed would have the greatest effect on care costs and built a series of multivariable regression models grouping patients by congenital lesion to examine the relative contribution of the specified variables to total annual inpatient cost. We analyzed a total of 68,314 patients aged 57 ± 18.6 years, 51% of whom were women. The multivariable regression model had an overall R(2) of 0.35. Readmission was responsible for 10.3% of annual inpatient cost among all patients with ACHD and had the greatest effect on inpatient care cost for each congenital lesion except Eisenmenger syndrome and conotruncal abnormalities, for both of which it was the second most significant contributor. Other major contributors to annual inpatient care costs included length of stay and operative procedures. In conclusion, rehospitalization is the most significant contributor to annual inpatient cost for individual patients with ACHD in the United States, regardless of underlying anatomy.


[Misinterpretation of fetal high voltage and lightning accidents].
From medicolegal practice it is known that in deaths caused by low voltage, electric marks may be absent or inconspicuous so that they may remain undetected during the scene examination. That this may happen even in fatal high-voltage accidents is demonstrated by 4 examples from our own autopsy material. The cases reported shared the following features: The decedents were found outdoors under a high-voltage line with a several metres long conductive object being in the immediate vicinity of the body; no extensive burns as those seen after the impact of an electric arc; inconspicuous electric marks on the hands; clearly visible electrothermal skin lesions limited to body regions covered by clothing (especially soles of the feet). Another case report demonstrates that even fatal lightning accidents are not always recognized correctly.


[A comparative analysis of energy process inhibitors on the efficiency of phage infection in staphylococci].
The study of the effect of KCN, DCCD and CCCP as inhibitors of the energy yielding processes showed that the efficacy of phage infection depended on respiration, proton ATPase, and proton electrochemical potential of hydrogen ions. There was a 49.5-68.0% decrease of the efficacy of phage infection after addition of the above mentioned inhibitors at the period of the contact of cells with bacteriophages at the stage of the phage nucleic acid transfer. The Embden-Meyerhof-Parnas route inhibitors NaF and CH2ICOOH less affected the efficacy of phage infection. The same effect was observed during addition of Na3AsO4 as the ATP synthesis inhibitor. This efficacy decrease was probably due the inhibition of the processes of the substrate level phosphorylation and the deplete of the intracellular ATP content.


Determination of national midwifery ethical values and ethical codes: in Turkey.
It is important to define and practice ethical rules and codes for professionalisation. Several national and international associations have determined midwifery ethical codes. In Turkey, ethical rules and codes that would facilitate midwifery becoming professionalised have not yet been determined. This study was planned to contribute to the professionalisation of midwifery by determining national ethical values and codes. A total of 1067 Turkish midwives completed the survey. The most prevalent values of Turkish midwives were care for mother-child health, responsibility and professional adequacy. The preferred professional codes chosen by Turkish midwives were absence of conflicts of interest, respect for privacy, avoidance of deception, reporting of faulty practices, consideration of mothers and newborns as separate beings and prevention of harm. In conclusion, cultural values, beliefs and expectations of society cannot be underestimated, although the international professional values and codes of ethics contribute significantly to professionalisation of the midwifery profession.


Constitutive and Inducible Innate Responses in Cells Infected by HSV-1-Derived Amplicon Vectors.
Amplicons are helper-dependent herpes simplex virus type 1 (HSV-1)-based vectors that can deliver very large foreign DNA sequences and, as such, are good candidates both for gene delivery and vaccine development. However, many studies have shown that innate constitutive or induced cellular responses, elicited or activated by the entry of HSV-1 particles, can play a significant role in the control of transgenic expression and in the induction of inflammatory responses. Moreover, transgene expression from helper-free amplicon stocks is often weak and transient, depending on the particular type of infected cells, suggesting that cellular responses could be also responsible for the silencing of amplicon-mediated transgene expression. This review summarizes the current experimental evidence underlying these latter concepts, focusing on the impact on transgene expression of very-early interactions between amplicon particles and the infected cells, and speculates on possible ways to counteract the cellular protective mechanisms, thus allowing stable transgene expression without enhancement of vector toxicity.