Development of insulin antibodies, metabolic control and B-cell function in newly diagnosed insulin dependent diabetic children treated with monocomponent human insulin or monocomponent porcine insulin.
One hundred and thirty eight patients participated in a two-year randomized, double-blind multicentre trial to compare monocomponent human insulin and porcine insulin in the treatment of newly diagnosed insulin dependent diabetic children with respect to development of insulin antibodies, metabolic control and B-cell function. There was no difference between the two patient groups throughout treatment either in the level of IgG insulin binding or the percentage of patients with insulin antibodies (IgG-insulin greater than 0.012 U/l). However, the estimated mean of log insulin binding values in the antibody positive patients alone was significantly lower (p less than 0.05) in the human insulin treated group at all times apart from 1 and 18 months (e.g., human insulin group at one and two years: 0.104 and 0.152 U/l, porcine insulin group at one and two years: 0.162 and 0.212 U/l). The insulin antibodies in both patient groups bound equivalent amounts of human and porcine insulin tracer. Metabolic control, insulin dosage and B-cell function in the two treatment groups were similar throughout the treatment period. It is concluded that in newly diagnosed insulin dependent diabetic children monocomponent human insulin is slightly less immunogenic than monocomponent porcine insulin, and equally effective in overall metabolic control.


Adiposity and carotid-intima media thickness in children and adolescents: a systematic review.
Adiposity in childhood is associated with later cardiovascular disease (CVD), but it is unclear whether this relationship is independent of other risk factors experienced in later life, such as smoking and hypertension. Carotid-intima media thickness (cIMT) is a measure of subclinical atherosclerosis that may be used to assess CVD risk in young people. The aim of this study was to examine the relationship between adiposity and cIMT in children and adolescents. We searched Medline, Embase, Global Health, and CINAHL Plus electronic databases (1980-2014). Population-based observational studies that reported a measure of association between objectively-measured adiposity and cIMT in childhood were included in this review. Twenty-two cross-sectional studies were included (n = 7,366 children and adolescents). Thirteen of nineteen studies conducted in adolescent populations (mean age ≥ 12 years, n = 5,986) reported positive associations between cIMT and adiposity measures (correlation coefficients 0.13 to 0.59). Three studies of pre-adolescent populations (n = 1,380) reported mixed evidence, two studies finding no evidence of a correlation, and one an inverse relationship between skinfolds and cIMT. Included studies did not report an adiposity threshold for subclinical atherosclerosis. Based on studies conducted mostly in Western Europe and the US, adiposity does not appear to be associated with cIMT in pre-adolescents, but may be associated in adolescents. If further studies confirm these findings, a focus on cardiovascular disease prevention efforts in pre-adolescence, before arterial changes have emerged, may be justified.


Disturbed tryptophan metabolism correlating to progression and metastasis of esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies worldwide. Lymph node metastasis is the leading cause of death in ESCC patients. To identify early diagnostic and prognostic biomarkers of ESCC and elucidate underlying pathogenesis of the disease, a targeted metabolomics strategy based on liquid chromatography combined with tandem mass spectrometry was applied to explore tryptophan metabolism between ESCC patients, metastatic ESCC patients (mESCC), and healthy controls. Statistical analysis on metabolite expression abundance and compound concentration ratio was conducted to discriminate patients from healthy controls. The concentration ratio of kynurenine, 5-hydroxytryptophan, 5-hydroxyindole-3-acetic acid, 5-hydroxytryptamine to their precursor tryptophan were identified as potential biomarkers, presenting high diagnostic capacity for distinguishing ESCC and mESCC patients from healthy controls. Moreover, a prognostic prediction model was also built on these ratios to distinguish metastasis patients from non-metastasis patients successfully. The high performance of ESCC prediction models suggest that concentration ratios of compounds may be used as biomarkers for early diagnosis and prognosis of the disease. In addition, concentration ratios of compounds show a progressively increased trend from non-metastasis to metastasis patients compared with healthy controls, which is in accordance with process of malignant transformation of ESCC. This interested finding suggests that disturbed tryptophan metabolism is correlated to progression and metastasis of ESCC since concentration ratios of compounds reflect activity of enzymes involved in tryptophan metabolism. This study reveals the impact of tryptophan metabolism to tumorigenesis and metastasis of ESCC, which help biologists investigate mechanism of the disease.


Human Term Pregnancy Decidual NK Cells Generate Distinct Cytotoxic Responses.
Decidual NK cells (dNK) are the main lymphocyte population in early pregnancy decidual mucosa. Although dNK decrease during pregnancy, they remain present in decidual tissues at term. First trimester dNK facilitate trophoblast invasion, provide protection against infections, and were shown to have many differences in their expression of NKRs, cytokines, and cytolytic capacity compared with peripheral blood NK cells (pNK). However, only limited data are available on the phenotype and function of term pregnancy dNK. In this study, dNK from human term pregnancy decidua basalis and decidua parietalis tissues were compared with pNK and first trimester dNK. Profound differences were found, including: 1) term pregnancy dNK have an increased degranulation response to K562 and PMA/ionomycin but lower capacity to respond to human CMV-infected cells; 2) term pregnancy dNK are not skewed toward recognition of HLA-C, as was previously shown for first trimester dNK; and 3) protein and gene expression profiles identified multiple differences between pNK, first trimester, and term pregnancy dNK, suggesting term pregnancy dNK are a distinct type of NK cells. Understanding the role of dNK throughout pregnancy is of high clinical relevance for studies aiming to prevent placental inflammatory disorders as well as maternal-to-fetal transmission of pathogens.


Transgenic mouse models for myotonic dystrophy type 1 (DM1).
The study of animal models for myotonic dystrophy type 1 (DM1) has helped us to 'de- and reconstruct' our ideas on how the highly variable multisystemic constellation of disease features can be caused by only one type of event, i.e., the expansion of a perfect (CTG)(n) repeat in the DM1 locus on 19q. Evidence is now accumulating that cell type, cell state and species dependent activities of the DNA replication/repair/recombination machinery contribute to the intergenerational and somatic behavior of the (CTG)(n) repeat at the DNA level. At the RNA level, a gain-of-function mechanism, with dominant toxic effects of (CUG)(n) repeat containing transcripts, probably has a central role in DM1 pathology. Parallel study of DM2, a closely related form of myotonic dystrophy, has revealed a similar mechanism, but also made clear that part of the attention should remain focused on a possible role for candidate loss-of-function genes from the DM1 locus itself (like DMWD, DMPK and SIX5) or elsewhere in the genome, to find explanations for clinical aspects that are unique to DM1. This review will focus on new insight regarding structure-function features of candidate genes involved in DM1 pathobiology, and on the mechanisms of expansion and disease pathology that have now partly been disclosed with the help of transgenic animal models.


[Effect of the new propofol target controlled infusion system in children undergoing high ligation of hernial sac].
To discuss the effect of the new target controlled infusion (TCI) system in Chinese children undergoing minor operation and compared with TCI system with Marsh parameters. Ninety ASA I, aged 3 - 5 yrs children undergoing elective unilateral high ligation of hernial sac under general anesthesia were randomly divided into group L (n = 45) and group M (n = 45) 2 groups. All subjects were unpremedicated. Systolic blood pressure (SBP), diastolic blood pressure (DBP), ECG, SpO2 and BIS were monitored. Patients of Group L and group M were anesthetized with propofol by Lian propofol TCI system and Marsh system respectively, combined with regional block. The target plasma concentration of TCI system was set at 6 microg/ml initially and up-regulated 1 microg/ml gradually if obvious body movement occurred while skin incision. If the target plasma concentration up to 8 microg/ml but there still had body movement, the TCI venous anesthesia was replaced by inhaled anesthesia. HR, RR, SBP, DBP and BIS were recorded in time points of baseline (T(0)), after the induction (T(1)), skin incision (T(2)), 3, 5 min after skin incision (T(3), T(4)), the end of operation (T(5)). Complications, the awakening time and the number of cases which anesthetized with different propofol plasma concentrations or inhaled anesthesia were recorded respectively as well. The number of cases which completed the operation under TCI plasma concentration 6 microg/ml in group L were significantly more than those in group M (P < 0.01). There were significantly different of T(1)-T(4) values of HR, RR, SBP, DBP and BIS in group M (P < 0.05), but not in group L. Compared with group L, T(2)-T(4) values of HR, RR, SBP, DBP and BIS were higher in group M (P < 0.05 or 0.01). Complications were lower in group L than those in group M. Compared with Marsh system, propofol 6 microg/ml plasma concentration with the new target controlled infusion system applied in Chinese children undergoing unilateral high ligation of hernial sac could maintain stable hemodynamics, less stress reaction and complications.


Genome annotation of five Mycoplasma canis strains.
To understand its potential to cause invasive disease, the genome of Mycoplasma canis strain PG14(T) from a dog's throat was compared to those of isolates from the genital tract or brain of dogs. The average nucleotide identity between strain pairs is 98%, and their genome annotations are similar.


Bone and Soft Tissue Response in Bone-Level Implants Restored with Platform Switching: A 5-Year Clinical Prospective Study.
The aim of this prospective study was to evaluate radiographic levels of peri-implant bone crest as well as soft tissue response, papilla height, and buccal mucosa recession, in bone-level implants restored with platform switching after 1-year and 5-year follow-ups. This prospective study called for the placement of 59 implants to obtain a target of 90% power. To compensate for possible dropouts, the sample size was adjusted to 67 implants. To assess marginal bone level changes, periapical radiographs were taken at baseline, 1 year, and 5 years after the definitive restorations. Peri-implant soft tissue modifications were evaluated by performing a photographic sequence at 15 days, 1 year, and 5 years after implant restoration. Parameters measured were: (1) distance from the tip of the papilla to the contact point and (2) apicocoronal crown length. A one-way analysis of variance (ANOVA rank test) was used to compare quantitative data among the three time points studied. Mean marginal bone level changes were as follows: -0.06 ± 0.32 mm from baseline to 1 year, -0.23 ± 0.38 mm from 1 to 5 years, and -0.28 ± 0.45 mm from baseline to 5 years. In bone-level outcomes, no statistically significant differences were found between baseline and 1 year, while the mean differences between 1 and 5 years and baseline and 5 years showed statistically significant differences. In the soft tissue analysis, the distance from the tip of the papilla to the contact point showed the following values: baseline, 2.08 mm; 1 year, 1.54 mm; 5 years, 1.31 mm. No statistically significant differences were found between baseline and 1 year, whereas statistically significant differences between 1 and 5 years and baseline and 5 years were found. Apicocoronal crown length measurements showed the following values: baseline, 9.44 mm; 1 year, 9.28 mm; 5 years, 9.81 mm. No significant differences were found between times studied. This prospective clinical study of 67 bone-level implants restored according to the platform-switching concept reported that radiographic levels of peri-implant bone crest were statistically significant between 1 and 5 years and baseline and 5 years. For the soft tissue response, the greatest reduction in the distance from the papilla to the contact point from 1 to 5 years and baseline to 5 years was observed. No significant differences were shown in the buccal margin.


RNA-stable isotope probing: from carbon flow within key microbiota to targeted transcriptomes.
Stable isotope probing of RNA has enthused researchers right from its first introduction in 2002. The concept of a labelling-based detection of process-targeted microbes independent of cellular replication or growth has allowed for a much more direct handle on functionally relevant microbiota than by labelling of other biomarkers. This has led to a widespread application of the technology, and breakthroughs in our understanding of carbon flow in natural microbiomes, autotrophic and heterotrophic physiologies, microbial food webs, host-microbe interactions and environmental biotechnology. Recent studies detecting labelled mRNA demonstrate that RNA-SIP is not limited to the analysis of rRNA, but is currently developing towards an approach for accessing targeted transcriptomes. In combination with next-generation sequencing and other methodological advances, RNA-SIP will continue to deliver invaluable insights into the functioning of microbial communities.


Evaluating the effect of horizontal transmission on the stability of plasmids under different selection regimes.
In theory, plasmids can only be maintained in a population when the rate of horizontal gene transfer is larger than the combined effect of segregational loss and the decrease of fitness associated with plasmid carriage. Recent advances in genome sequencing have shown, however, that a large fraction of plasmids do not carry the genes necessary for conjugation or mobilization. So, how are so-called non-transmissible plasmids able to persist? In order to address this question, we examined a previously published evolutionary model based on the interaction between P. aeruginosa and the non-transmissible plasmid pNUK73. Both our in silico and in vitro results demonstrated that, although compensatory adaptation can decrease the rate of plasmid decay, the conditions for the maintenance of a non-transmissible plasmid are very stringent if the genes it carries are not beneficial to the bacterial host. This result suggests that apparently non-transmissible plasmids may still experience episodes of horizontal gene transfer occurring at very low frequencies, and that these scattered transmission events are sufficient to stabilize these plasmids. We conclude by discussing different genomic and microbiological approaches that could allow for the detection of these rare transmission events and thus to obtain a reliable estimate of the rate of horizontal gene transfer.


Dimeric Potassium Amide-Catalyzed α-Alkylation of Benzyl Sulfides and 1,3-Dithianes.
The first catalytic α-alkylation reaction of benzyl sulfides and 1,3-dithianes with styrenes and conjugated dienes was developed under mild conditions by using a readily available Brønsted base potassium bis(trimethylsilyl)amide (KHMDS) as catalyst. The reaction displayed good functional group tolerance, high efficiency, and excellent chemoselectivity. A series of desired alkylation products were obtained in good to high yield. Preliminary mechanism studies suggested that two of the potassium amide catalyst molecules worked together in the catalytic cycle.


Cytoskeletal activation of a checkpoint kinase.
The assembly of cytoskeletal structures is coupled to other cellular processes. We have studied the molecular mechanism by which assembly of the yeast septin cytoskeleton is monitored and coordinated with cell cycle progression by analyzing a key regulatory protein kinase, Hsl1, that becomes activated only when the septin cytoskeleton is properly assembled. We first identified a regulatory region of Hsl1 that physically associates with the kinase domain and found that it performs an autoinhibitory function both in vivo and in vitro. Several septin binding domains lie near and overlap the inhibitory domain; these are important for Hsl1 function, and binding of two septins, Cdc11 and Cdc12, relieves the autoinhibition imposed by the kinase inhibitory domain in vitro. Our results suggest that binding to multiple septins activates Hsl1 kinase activity, thereby promoting cell cycle progression. The high conservation of Hsl1 indicates that similar mechanisms may monitor cytoskeletal organization in other eukaryotes.


A lens-specific co-injection marker for medaka transgenesis.
Recent advances in generating transgenic fish have improved the efficiency of germline transmission and enabled the generation of large numbers of transgenic animals. A suitable co-injection marker may help facilitate the preselection of transgenic embryos. For this purpose, a lens-specific marker appears to be a suitable candidate since the lens is a well-defined tissue that is easily accessible for examination of reporter gene expression. We constructed reporter vectors including the mouse gamma-F crystallin (mgammaF-Cry) promoter, which drives high levels of lens-specific heterologous expression of the reporter gene and thereby enables easy sorting of transgenic fish.


Intracellular calcium oscillations induced in a T-cell line by a weak 50 Hz magnetic field.
Applied weak magnetic fields have been shown to affect cellular activity on several levels, but the mechanisms involved remain elusive. We have decided to study an early signal transduction event in the human T cell line Jurkat; oscillations of free [Ca2+]i, of the type seen by crosslinking the CD3 complex. Cells were exposed to a 50 Hz, 0.1 mT, sinusoidal magnetic field while intracellular free calcium was measured in individual cells, using fura-2 as a probe. An acute response was observed with oscillatory increases in [Ca2+]i, which subsided when the field was turned off. The effect of the magnetic field on [Ca2+]i was comparable to that achieved by an anti-CD3 monoclonal antibody.


Use of propensity score technique to account for exposure-related covariates: an example and lesson.
In observational research, propensity score techniques can be used to account for baseline differences between compared therapies. Although propensity scores are used increasingly often, their limitations in settings without complete data may not be recognized. We sought to evaluate the ability of propensity score matching to mitigate confounding by indication in an observational study of the effect of statin therapy on acute myocardial infarction (AMI). Matching was performed at random, and with propensity scores that incorporated a reduced or expanded set of variables. RESEARCH DESIGN/SUBJECTS: This was a propensity score matched cohort study using members of a health insurer database. Exposure to statin therapy was assessed at the beginning of follow-up with all cohort members being statin initiators or noninitiators, and the outcome of AMI was identified on the basis of claims codes. Matching on the basis of the propensity score provided results that are similar in magnitude to randomized clinical trials, suggesting that confounding was mitigated. However, matching on a propensity score created on a reduced set of variables yielded a result that suggested no effect of statin therapy, and demonstrated substantial imbalance on some variables that were not part of the propensity score. Propensity score matching can balance with respect to variables not explicitly included in the score, but external data are required to evaluate this.


Implications for the establishment of accelerated fatigue test protocols for prosthetic heart valves.
The goal of this research is to establish a reliable methodology for accelerated fatigue tests of prosthetic heart valves. A polymer valve was the subject, and the influence of various drive parameters on durability was investigated in three different machines. Valve lifetime was notably shortened by increasing the cyclic rate or stroke even though the maximum pressure difference at valve closure was maintained at 120 mm Hg. These results demonstrate that adjustment of the maximum transvalvular pressure is not sufficient to ensure tests are conducted under the same conditions and indicate that measurement of the dynamic load would be more efficacious. Moreover, the locations of tears sustained in the accelerated tests differed from those encountered in an animal experiment although in both cases the locations were entirely consistent with the areas of strain concentration revealed by finite element analysis. These findings should be discussed during a revision of ISO 5840.


Topoisomerase I as a target of erlotinib and gefitinib: efficacy of combined treatments with camptothecin.
Topoisomerases are essential nuclear enzymes that work to resolve topological problems that normally occur during DNA metabolism. Their involvement in crucial DNA associated-processes, such as replication, transcription and repair, mark them as a target of chemotherapeutic drugs such as camptothecins (CPTs). Therefore, finding other agents that may alter their activity is of great importance. Previous data showed that certain tyrosine kinase antagonists, tyrphostins, inhibit the catalytic activity of the cellular topoisomerase I (topo I). We examined the effect of clinically used tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, on topo I in breast and prostate cancer cells. While erlotinib and gefitinib inhibit cellular topo I in treated cells without affecting the levels of the enzyme protein, in vitro assays show that erlotinib, but not gefitinib, inhibits the DNA relaxation activity of purified topo I. Erlotinib was found to reduce the DNA-binding ability of topo I, however, the reduction in topo I activity in gefitinib-treated cells is probably due to post-translational modifications of the enzyme protein. A combined treatment of either erlotinib or gefitinib with CPT increased the effect of CPT on the activity of cellular topo I, which supports the increased anticancer effect observed in MCF7 cells. These results suggest that topo I is a novel target of erlotinib and a combination of TKIs with topo I inhibitors may be an effective treatment for breast cancer.


Closure of fascial incisions made at the time of laparoscopy: development of a device.
Incisional hernias follow approximately 3% of major laparoscopic procedures when the fascia is not adequately closed. Fascial closure, however, is difficult when skin incisions are small and subcutaneous tissue is thick. We report the development of a self-contained device that sutures the anterior abdominal wall peritoneum and fascia at the completion of laparoscopic surgery without extending the cutaneous incision.


Quantum targeted energy transfer through machine learning tools.
In quantum targeted energy transfer, bosons are transferred from a certain crystal site to an alternative one, utilizing a nonlinear resonance configuration similar to the classical targeted energy transfer. We use a computational method based on machine learning algorithms in order to investigate selectivity as well as efficiency of the quantum transfer in the context of a dimer and a trimer system. We find that our method identifies resonant quantum transfer paths that allow boson transfer in unison. The method is readily extensible to larger lattice systems involving nonlinear resonances.


[Advances in the physiopathology of epileptogenesis: metabolic aspects in vivo].
This communication shows how proton magnetic resonance spectroscopy (MRS) is currently being employed in the study or the diagnosis of epilepsy. With this goal, the kind of biochemical information of cerebral parenchyma available with this non invasive technique is first introduced in a succinct way. The value of this metabolic information is then illustrated through several cases of temporal and extratemporal epilepsy, for which magnetic resonance imaging was either non diagnostic or uncertain. In this context, the asymmetry index, very useful for the lateralization of epileptogenic foci on the basis of quantitative spectroscopic criteria, is defined. Finally, other potentials of MRS, beyond its ability to elucidate the existence of neuronal damage in the epileptogenic zone, are considered. Hence, cases with postictally increased lactate, or increased glutamine/glutamate without apparent neuronal damage, are presented as good examples of the diagnostic or lateralizing value of MRS.


[Osler's disease--a risk factor for stroke].
Osler's disease is an inherited disease of blood vessels that causes haemorrhage from the nasal mucosa, gastrointestinal tract, lungs or the urinary tract. Patients may also have abnormal intracerebral vessels. A patient with Osler's disease and recurrent epistaxis suffered a cerebellar infarction. He had no other risk factors for stroke. An arteriovenous fistula was demonstrated in the right lung. This fistula was the probable source or aberrant pathway of an embolus to the cerebellum. The patient was treated with endovascular occlusion of the fistula to prevent further emboli to the brain. Embolisation of thrombi from arteriovenous fistulae in the lungs is a rare cause of stroke, though important since secondary prophylaxis is very effective. Physicians should consider this possibility in the occasional patient with embolic stroke in whom no other risk factor is established.


Highly Selective and Sensitive Two-Photon Fluorescence Probe for Endogenous Peroxynitrite Detection and Its Applications in Living Cells and Tissues.
A new two-photon fluorescence probe for endogenous peroxynitrite (ONOO-) detection was designed and synthesized. The probe exhibits good selectivity and sensitivity for ONOO- in phosphate-buffered saline solution with a low detection limit (3.5 × 10-8 M). Furthermore, the probe displays good performance in detecting endogenous ONOO-, not only in RAW 264.7 cells but also in rat hippocampal tissue, with a high two-photon cross-section value (δ ≈ 100 GM) at a deep depth of 120 μm.


When is Genomic Testing Cost-Effective? Testing for Lynch Syndrome in Patients with Newly-Diagnosed Colorectal Cancer and Their Relatives.
Varying estimates of the cost-effectiveness of genomic testing applications can reflect differences in study questions, settings, methods and assumptions. This review compares recently published cost-effectiveness analyses of testing strategies for Lynch Syndrome (LS) in tumors from patients newly diagnosed with colorectal cancer (CRC) for either all adult patients or patients up to age 70 along with cascade testing of relatives of probands. Seven studies published from 2010 through 2015 were identified and summarized. Five studies analyzed the universal offer of testing to adult patients with CRC and two others analyzed testing patients up to age 70; all except one reported incremental cost-effectiveness ratios (ICERs) < $ 100,000 per life-year or quality-adjusted life-year gained. Three studies found lower ICERs for selective testing strategies using family history-based predictive models compared with universal testing. However, those calculations were based on estimates of sensitivity of predictive models derived from research studies, and it is unclear how sensitive such models are in routine clinical practice. Key model parameters that are influential in ICER estimates included 1) the number of first-degree relatives tested per proband identified with LS and 2) the cost of gene sequencing. Others include the frequency of intensive colonoscopic surveillance, the cost of colonoscopy, and the inclusion of extracolonic surveillance and prevention options.


Vermifiltration as a sustainable natural treatment technology for the treatment and reuse of wastewater: A review.
With increasing urbanization and industrialization, the scarcity of freshwater is becoming rampant. To counteract this, authorities all over the world are forced to consider the treatment and reuse of the wastewater produced by either industries or domestic units. After an extensive literature survey, vermifiltration coupled with/without macrophyte has been identified as one of the best sustainable, natural and eco-friendly technology for the treatment and reuse of wastewater. Till date, it has been successfully applied for treating domestic wastewater. However, the results from very limited industrial applications are also encouraging and proving its worth for industrial wastewater remediation. The present review on vermifiltration deals with the mechanisms involved and its current status for the remediation and reutilisation of the effluents generated from domestic and industrial premises. The review successfully identifies and explicitly discusses the mechanisms involved in the vermifiltration. The review exhaustively discusses the performance of vermifiltration and identifies the factors contributing to the performance of vermifiltration, which could be of help in designing of the field scale vermifilter based treatment plant. The review identifies the limitations associated with the vermifiltration and suggests possible alternatives, aimed to improve its performance and applicability. The aim of this review is to bring the attention of prospective researchers to study each and every aspect related to the vermifiltration so that it may be adopted as a reliable and dependable technology for the remediation of several industrial effluents meeting the concept of "Zero discharge".


University-industry collaboration as a driver of digital transformation: Types, benefits and enablers.
University-Industry collaboration as a driver of digital transformation ultimately depends on the engagement and relationship between individual academics and industry practitioners as partners in a trust relationship. This paper describes the personal ('lived') experiences of academics and industry practitioners. The types, benefits, and enablers of the collaboration were investigated during semi-structured face-to-face interviews with industry partners and academic staff from the Science, Technology, Engineering and Mathematics (STEM) unit at the University of Enterprise in Australia. The types of collaboration included research activities, sharing facilities and equipment, innovation and commercialisation, collaboration involving students projects, collaborative teaching and learning, and sharing facilities and equipment. The benefits of the collaboration include access to valuable resources, validation of work, learning and teaching opportunities, financial benefits, improved reputation and career progression. The enablers of collaboration have been clustered into institutional, output, framework, and relationship factors. In this paper we focus on relationship factors and institutional enablers such as stakeholder engagement. The research is represented in a UA-IP Collaboration Model indicating the types (what), benefits (why), and enablers (how) of academic-practitioner collaboration. Universities and businesses from a variety of industries can benefit from the results of the presented research.


Cortical and Subcortical Contributions to Short-Term Memory for Orienting Movements.
Neural activity in frontal cortical areas has been causally linked to short-term memory (STM), but whether this activity is necessary for forming, maintaining, or reading out STM remains unclear. In rats performing a memory-guided orienting task, the frontal orienting fields in cortex (FOF) are considered critical for STM maintenance, and during each trial display a monotonically increasing neural encoding for STM. Here, we transiently inactivated either the FOF or the superior colliculus and found that the resulting impairments in memory-guided orienting performance followed a monotonically decreasing time course, surprisingly opposite to the neural encoding. A dynamical attractor model in which STM relies equally on cortical and subcortical regions reconciled the encoding and inactivation data. We confirmed key predictions of the model, including a time-dependent relationship between trial difficulty and perturbability, and substantial, supralinear, impairment following simultaneous inactivation of the FOF and superior colliculus during memory maintenance.


Identification of Odor Blend Used by Caenorhabditis elegans for Pathogen Recognition.
Animals have evolved specialized pathways to detect appropriate food sources and avoid harmful ones. Caenorhabditis elegans can distinguish among the odors of various species of bacteria, its major food source, but little is known about what specific chemical cue or combination of chemical cues C. elegans uses to detect and recognize different microbes. Here, we examine the strong innate attraction of C. elegans for the odor of the pathogenic bacterium, Serratia marcescens. This initial attraction likely facilitates ingestion and infection of the C. elegans host. Using solid-phase microextraction and gas chromatography coupled with mass spectrometry, we identify 5 volatile odors released by S. marcescens and identify those that are attractive to C. elegans. We use genetic methods to show that the amphid chemosensory neuron, AWCON, senses both S. marcescens-released 2-butanone and acetone and drives attraction to S. marcescens. In C. elegans, pairing a single odorant with food deprivation results in a reduced attractive response for that specific odor. We find that pairing the natural odor of S. marcescens with food deprivation results in a reduced attraction for the natural odor of S. marcescens and a similar reduced attraction for the synthetic blend of acetone and 2-butanone. This result indicates that only 2 odorants represent the more complex odor bouquet of S. marcescens. Although bacterial-released volatiles have long been known to be attractive to C. elegans, this study defines for the first time specific volatile cues that represent a particular bacterium to C. elegans.


Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.
The coagulation protein von Willebrand Factor (VWF) is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood. To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies. We measured VWF antigen (VWF:Ag), VWF propeptide (VWFpp), Factor VIII (FVIII), and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF) of VWF in two pregnancies which had samples from multiple trimesters. VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation. These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.


Micrometastasis in lymph nodes of mucosal gastric cancer.
BACKGROUND: Endoscopic mucosal resection is frequently used in the treatment of mucosal gastric cancer. Micrometastasis in the lymph nodes of mucosal gastric cancer remains unclear.METHODS: We examined 2526 lymph nodes from 84 patients with mucosal gastric cancer. Two consecutive sections were prepared, for simultaneous staining with hematoxylin and eosin and immunostaining with CAM 5.2 monoclonal antibody against cytokeratin (CK), respectively. A clinicopathological comparison was made between patients with and without lymph node involvement.RESULTS: Lymph node involvement was detected in 45 of 2526 (1.8%) lymph nodes. The incidence of nodal involvement was significantly increased, from 1.2% (1/84 patients) with hematoxylin and eosin staining, to 19% (16/84 patients) with CK immunostaining. Although no significant difference was found, micrometastasis to lymph nodes was more frequently detected in tumors larger than 1.0 cm (15/72 patients, 21%) than in those less than or equal to 1.0 cm (1/12 patients; 8%, P = 0.307). However, discrete CK-positive cancer cells or clusters of CK-positive cancer cells were detected only in tumors larger than 2 cm.CONCLUSION: Because mucosal gastric cancer of more than 1.0 cm in superficial diameter may indicate a risk of micrometastasis to lymph nodes, endoscopic mucosal resection is not recommended for these patients.


Bioceramic Implant Induces Bone Healing of Cranial Defects.
Autologous bone or inert alloplastic materials used in cranial reconstructions are techniques that are associated with resorption, infection, and implant exposure. As an alternative, a calcium phosphate-based implant was developed and previously shown to potentially stimulate bone growth. We here uncover evidence of induced bone formation in 2 patients. Histological examination 9 months postoperatively showed multinuclear cells in the central defect zone and bone ingrowth in the bone-implant border zone. An increased expression of bone-associated markers was detected. The other patient was investigated 50 months postoperatively. Histological examination revealed ceramic materials covered by vascularized compact bone. The bone regenerative effect induced by the implant may potentially improve long-term clinical outcome compared with conventional techniques, which needs to be verified in a clinical study.


[Postpartum evaluation of amylin secretion in gestational diabetes mellitus].
Amylin (Islet Amyloid Pancreatic Polypeptide - IAPP) is a hormone cosecreted with insulin by pancreatic beta cells in a pulsatile pattern. Recent reports point to its essential part in glucose homeostasis. Postpartum evaluation of IAPP release in Gestational Diabetes Mellitus (GDM) patients was performed. Our data were compared to insulin and peptide-C secretion patterns. We were not able to demonstrate a dynamic increase of IAPP in response to glucagon stimuli. However, related to GDM, puerperal IAPP levels were significantly higher than in normal controls. Lack of postpartum amylin response to glucagon stimulation might be interpreted as a primary result of previously reported increases in circulatory levels of IAPP during pregnancy complicated by GDM. Post partum elevated IAPP may be a useful marker to identify patients with high risk of type 2 diabetes mellitus.


Renal Trauma Increases Risk of Future Hypertension.
To determine if traumatic renal injuries or computed tomography (CT) findings are predictive of hypertension (HTN) development following injury. A retrospective review of a renal trauma database was performed from 1995 to 2015. Renal injuries were graded by the American Association for the Surgery of Trauma system, with high-grade defined as IV or V. Nonrenal genitourinary trauma (ie bladder, penile, urethral, and testicular) patients were selected as controls. Patients with a diagnosis of HTN before their trauma or those lacking follow-up were excluded. Risk factors associated with HTN following trauma were identified using multivariable regression with propensity scoring. In total, 163 patients had a renal injury and 60 had nonrenal, genitourinary injuries. The median age was 31 years (interquartile range 23-43) with median follow-up of 4.7 years (interquartile range 1.9-8.5). Twenty-three (14%) patients with renal trauma were newly diagnosed with HTN on follow-up, compared with 2 (3%) in the control groups. (P = .02) After propensity quartile adjustment, patients with high-grade trauma had higher odds of developing HTN compared with low-grade renal trauma patients and controls (adjusted odds ratio 3.5, 95% confidence interval 1.3-9.3, P = .01). Patients with a midpole medial laceration and medial blood on CT had higher odds of developing HTN compared with patients without these characteristics (odds ratio 5.36, 95% confidence interval 1.3-22.6, P = .02). Increasing renal trauma grade is a risk factor for future development of HTN. CT findings at trauma presentation may be useful in stratifying patients who are at increased risk.


Function Follows Form: Oriented Substrate Nanotopography Overrides Neurite-Repulsive Schwann Cell-Astrocyte Barrier Formation in an In Vitro Model of Glial Scarring.
Schwann cell (SC) transplantation represents a promising therapeutic approach for traumatic spinal cord injury but is frustrated by barrier formation, preventing cell migration, and axonal regeneration at the interface between grafted SCs and reactive resident astrocytes (ACs). Although regenerating axons successfully extend into SC grafts, only a few cross the SC-AC interface to re-enter lesioned neuropil. To date, research has focused on identifying and modifying the molecular mechanisms underlying such scarring cell-cell interactions, while the influence of substrate topography remains largely unexplored. Using a recently modified cell confrontation assay to model SC-AC barrier formation in vitro, highly oriented poly(ε-caprolactone) nanofibers were observed to reduce AC reactivity, induce extensive oriented intermingling between SCs and ACs, and ultimately enable substantial neurite outgrowth from the SC compartment into the AC territory. It is anticipated that these findings will have important implications for the future design of biomaterial-based scaffolds for nervous tissue repair.


Correlation between pulse wave velocity and other measures of arterial stiffness in chronic kidney disease.
Pulse wave velocity (PWV), augmentation index (AIx) and time to first wave reflection (Tr) are all measures of arterial stiffness, but whether these parameters behave similarly in different populations is not well-understood. Given the large burden of cardiovascular disease in individuals with chronic kidney disease (CKD), assessing the relationship between vascular stiffness parameters in this population is important. A subset of 152 participants enrolled in the Chronic Renal Insufficiency Cohort Study had vascular stiffness parameters (aortic PWV, central AIx, and Tr) measured using the SphygmoCor system. Linear association between these parameters was assessed using Pearson correlation coefficients. Reproducibility across operators of the device was also tested within individuals. Association was largest between PWV and heart rate-adjusted AIx (AIx-75). The correlation coefficient was 0.371 (p = 0.0003) for ideal studies and 0.305 (p = 0.0001) for all technically acceptable studies. The association between ideal PWV and AIx-75 measurements was 0.361 (p = 0.005) for men and 0.423 (p = 0.01) for women. Bland-Altman plots comparing the mean value of PWV (n = 31) or AIx-75 (n = 21) when measured by 2 different individuals against the difference in their respective values demonstrate that both measures of arterial stiffness are reproducible across multiple technicians. Thus, we conclude that PWV and AIx-75, despite measuring different quantities in different units, are related measures of arterial stiffness and are reproducible across multiple operators in the population with CKD.


Analysis of the permissive association of a malaria T cell epitope with DR molecules.
In this study we examined the association of a promiscuous malaria T cell epitope, CS.T3, to different HLA-DR alleles. A large series of singly substituted or truncated variants of CS.T3 was prepared and tested for the ability to be recognised in association with, or to bind to, three distinct HLA-DR alleles (DR1, DRw11, and DRw14(w6)) and three natural variants of HLA-DRw11. We found that although association with the different DR molecules mapped to identical or closely overlapping regions of the peptide, distinct substitutions could drastically influence the capacity of the peptide to interact with one but not another of the three DR molecules tested. Based on analysis of the distribution of residues recognized by T cell clones restricted to the different DR alleles, we suggest that the peptide CS.T3 is not bound, at least for the three DR examined, as an alpha-helix. In addition we tested three subtypes of DRw11 as APC for the CS.T3 analogues and observed that the peptide is most likely bound in the same conformation to the three natural variants of the DRw11 molecule.


A novel and efficient synthesis of N,N-dialkylaminoisopropyl- and O-alkylisopropyl-2-(1-alkyl-2-oxopropylidene)phosphonohydrazido oximes--potential marine fish toxin analogues. Part 1.
A novel and efficient method for the synthesis of N,N-dialkylaminoisopropyl- and O-alkylisopropyl-2-(1-alkyl-2-oxopropylidene)phosphonohydrazido oximes (4) using activated silica as dehydrating agent has been developed. The reaction involves the condensation of substituted diacetyl monoxime and N,N-dialkylaminoisopropyl-phosphono hydrazide or O-alkylisopropylphosphono hydrazides and gave the corresponding analogues of a naturally occurring fish toxin in excellent yields under mild conditions.


Further characterization of the cardiovascular effects of the dopamine beta-hydroxylase inhibitor SK&F 102698 in conscious hypertensive rats.
The dopamine beta-hydroxylase inhibitor SK&F 102698 was characterized by studying its cardiovascular effects in hypertensive rats. The antihypertensive effects of SK&F 102698 (50 mg/kg p.o.) were studied in three different rat models of hypertension. In spontaneously hypertensive and deoxycorticosterone acetate-salt rats SK&F 102698 produced blood pressure reductions of approximately 21 and 23%, respectively. In contrast, SK&F 102698 did not produce a significant decrease in blood pressure in 2-kidney, 1-clip Goldblatt hypertensive rats. The antihypertensive mechanism of action of dopamine beta-hydroxylase inhibition was probed with the selective DA1-receptor antagonist SCH 23390, which produced an attenuation of the antihypertensive effects of SK&F 102698. Experiments were designed to separate the peripheral from the central components of the cardiovascular effects of SK&F 102698. In spinal cord stimulated pithed spontaneously hypertensive rats, SK&F 102698 reduced blood pressure but not heart rate, indicating a peripherally mediated vasodilation and a centrally mediated heart rate effect. Furthermore, when SK&F 102698 was administered directly into the fourth ventricle of conscious spontaneously hypertensive rats, a pronounced bradycardia and lowering of blood pressure was observed. SCH 23390 (200 micrograms/kg i.v.) and l-sulpiride (1 mg/kg i.v.) inhibited the cardiovascular effects of SK&F 102698 administered into the fourth ventricle. These data indicate that inhibition of dopamine beta-hydroxylase with SK&F 102698 results in both peripherally and centrally mediated cardiovascular effects and suggest that central dopamine receptors contribute to the control of systemic blood pressure in hypertensive models associated with an increased sympathetic outflow.


Transsphenoidal neurosurgery of intracranial neoplasm.
Because of the benign, rapid, and nontraumatizing nature of the extracranial transsphenoidal approach to the base of the skull, this procedure is indicated as the method of choice in nearly all cases of surgery for pituitary fossa and parasellar region access. Some of the largest pituitary chromophobe adenomas with voluminous suprasellar expansion have been successfully excised from below, as well as some calcified tumors, craniopharyngiomas, Rathke's pouch cysts, chordomas, chondromas, and meningiomas. At the other extreme, the smallest intrapituitary microadenomas (as little as 3 mm in diameter) were selectively removed under optic magnification with the surgical microscope. This method is now the most appropriate for the treatment of oversecreting pituitary disorders, even with normal-sized sella turcica (acromegaly - Cushing -galactorrhea). Early detection of intrapituitary microadenoma allows achievement of its selective excision with preservation of the normal gland. Thus, the ideal goal can be achieved by immediate biological cure of hyperpituitarism with preservation of other pituitary functions, resulting in normal physiological eupituitarism.


Analysing the performance of in vitro fertilization clinics in the United Kingdom.
During the past century, the manufacturing industry has achieved major successes in improving the quality of its products. An essential factor in these successes has been the use of Walter A. Shewhart's pioneering work in the economic control of variation, which culminated in the development of a simple yet powerful theory of variation, which classifies variation as having a common or special cause and thus guides the user to the most appropriate action to effect improvement. Using publicly available performance data, which includes percentage of live births and multiple births, for in vitro fertilization (IVF) clinics in the United Kingdom, we show a central role for Shewhart's approach in moving away from the limitations and controversies associated with performance league tables towards data analyses to support continual improvement. We outline strategies for dealing with common and special causes of variation in IVF clinic performance data.


BPA interferes with granulosa cell development and oocyte meiosis in mouse preantral follicles.
Bisphenol A (BPA) is an established environmental endocrine disruptor and can interfere with the development of female germ cells. However, the underlying mechanisms are still unclear. We investigated the effects of BPA on granulosa cell development and meiosis of oocytes using in vitro culture system of mouse preantral follicles. Preantral follicles from D14 mouse ovary were treated with 10 μg/mL BPA in vitro for 11 days. The adherent area of follicles was measured. On D11, cumulus cell expansion was observed. The meiosis recovery rate was calculated. Western blot detected P53, proliferating cell nuclear antigen (PCNA), estrogen receptor α (ERα), and cyclin B1. ELISA measured estrogen and progesterone levels. Immunofluorescence detected Cx37 on oocyte membrane. Gap junction communication was assessed. We found that BPA significantly promoted the expressions of PCNA and ERα in granulosa cells and the secretion of estrogen and progesterone by granulosa cells on D10 and significantly increased the attachment area of the follicles on D8 and D10. However, it reduced the expansion of cumulus cells, Cx37 expression, and the gap junction communication between cumulus cells and oocytes on D11. BPA promoted the recovery of oocytes from meiosis, interrupted the expression of cyclin B1 protein in arrested germinal vesicle breakdown (GVBD) oocytes, and reduced the in vitro maturation rate of oocytes. These GVBD oocytes were live without apoptosis or death. Conclusively, BPA disturbs the development of granulosa cells and the meiosis progression of oocytes by decreasing gap junction communication between oocytes and the granulosa cells as well as regulating cyclin B1 expression in GVBD oocytes.


Effects of maximal static apnea on antioxidant defenses in trained free divers.
To investigate the effects of maximal static apnea on plasma antioxidant status, oxidative stress, and antioxidant enzyme activities in trained free divers. Blood was taken from apnea-trained (Tr) and control (Con) subjects at baseline (B) and after one (A1), three (A3), and five (A5) apneas. Trolox equivalent antioxidant capacity (TEAC), ferric reducing ability of plasma (FRAP), uric acid, and bilirubin assays assessed plasma antioxidant status and malondialdehyde (MDA) quantified the oxidative stress response. The activities of erythrocyte antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were determined at baseline and after the fifth apnea. TEAC was significantly higher in divers versus controls after A1 (P < 0.05). A group effect of SOD activity indicated higher activity throughout the protocol in Tr (mean +/- SD; Con, 43.2 +/- 10.1 U.g Hb; Tr, 50.1 +/- 7.3 U.g Hb; P = 0.04). With no other group differences, the groups' data were combined. Apnea significantly increased SOD (B, 44.1 +/- 11.1 U.g Hb; A5, 48.1 +/- 7.5 U.g Hb; P < 0.05) and GPx activity (B, 60.5 +/- 14.9 U.g Hb; A5, 70.1 +/- 16.0 U.g Hb; P = 0.02); however, CAT activity decreased (B, 5.25 +/- 0.59 U.mg Hb; A5, 5.00 +/- 0.53 U.mg Hb; P = 0.03). MDA was unaffected by apnea (P = 0.32). Trained free divers have increased SOD activity during apnea; however, there is little difference in their antioxidant and oxidative stress responses compared with controls. In both groups, acute changes in antioxidant enzyme activities suggest that they may protect from excessive antioxidant depletion and oxidative stress during apnea.


Characterization of a pollen-preferential gene, BAN102, from Chinese cabbage.
We isolated and characterized a pollen-preferential gene, BAN102, from Chinese cabbage and analyzed the activity of its promoter. There were three or four copies of the BAN102 gene in the Chinese cabbage genome that specifically expressed in pollen and pollen tube. There were 2137 bp of BAN102 genomic clone comprising 186 bp of protein coding region, and 1178 bp of 5' and 773 bp of 3' non-coding regions. TATA box were located at 1071 nt of the promoter region while the polyadenylation signal and polyadenylation site were at 1470 and 1486 nt of the 3' non-coding region. BLAST search of BAN102 sequence showed that coding region of BAN102 gene was the greatest percent similarity with arabinogalactan protein (AGP23) gene from Arabidopsis thaliana. Promoter analysis using GUS gene as a reporter showed that the pollen-specificity of BAN102 resided within the -112 to -44 bp of proximal promoter from the transient expression in tobacco and Chinese cabbage plants.


Kinetic model for the ATP-dependent translocation of Saccharomyces cerevisiae RSC along double-stranded DNA.
The chromatin remodeling complex RSC from Saccharomyces cerevisiae is a DNA translocase that moves with directionality along double-stranded DNA in a reaction that is coupled to ATP hydrolysis. To better understand how this basic molecular motor functions, a novel method of analysis has been developed to study the kinetics of RSC translocation along double-stranded DNA. The data provided are consistent with RSC translocation occurring through a series of repeating uniform steps with an overall processivity of P = 0.949 +/- 0.003; this processivity corresponds to an average translocation distance of 20 +/- 1 base pairs (bp) before dissociation. Interestingly, a slow initiation process, following DNA binding, is required to make RSC competent for DNA translocation. These results are further discussed in the context of previously published studies of RSC and other DNA translocases.


Impacts of genetic correlation on the independent evolution of body mass and skeletal size in mammals.
Mammals show a predictable scaling relationship between limb bone size and body mass. This relationship has a genetic basis which likely evolved via natural selection, but it is unclear how much the genetic correlation between these traits in turn impacts their capacity to evolve independently. We selectively bred laboratory mice for increases in tibia length independent of body mass, to test the hypothesis that a genetic correlation with body mass constrains evolutionary change in tibia length. Over 14 generations, we produced mean tibia length increases of 9-13%, while mean body mass was unchanged, in selectively bred mice and random-bred controls. Using evolutionary scenarios with different selection and quantitative genetic parameters, we also found that this genetic correlation impedes the rate of evolutionary change in both traits, slowing increases in tibia length while preventing decreases in body mass, despite the latter's negative effect on fitness. Overall, results from this ongoing selection experiment suggest that parallel evolution of relatively longer hind limbs among rodents, for example in the context of strong competition for resources and niche partitioning in heterogeneous environments, may have occurred very rapidly on geological timescales, in spite of a moderately strong genetic correlation between tibia length and body mass.


Highly efficient exciton harvesting and charge transport in ternary blend solar cells based on wide- and low-bandgap polymers.
We have designed highly efficient ternary blend solar cells based on a wide-bandgap crystalline polymer, poly(3-hexylthiophene) (P3HT), and a low-bandgap polymer, poly[(4,4'-bis(2-ethylhexyl)dithieno[3,2-b:2'3'-d]silole)-2,6-diyl-alt-(2,1,3-benzothiadiazole)-4,7-diyl] (PSBTBT), and a fullerene derivative (PCBM). By using highly crystalline P3HT, high fill factors were obtained even for ternary blend solar cells, suggesting efficient charge transport due to large P3HT crystalline domains. In such large crystalline domains, some P3HT excitons could not diffuse into the interface with PCBM but can be collected in PSBTBT domains by efficient energy transfer because of large spectral overlap between the P3HT fluorescence and the PSBTBT absorption. Consequently, all the P3HT excitons can contribute to the photocurrent generation at the P3HT/PCBM interface and/or PSBTBT domains mixed with PCBM in the ternary blends. As a result, P3HT/PSBTBT/PCBM ternary blend solar cells exhibit a power conversion efficiency of 5.6%, which is even higher than those of both individual binary devices of P3HT/PCBM and PSBTBT/PCBM.


Catecholamines in aqueous humour of glaucoma patients.
Aqueous humour catecholamine concentrations were assayed in open angle glaucoma, and cataract patients during surgery, under general anaesthesia. Plasma catecholamines were measured at the same time. Aqueous humour noradrenaline is apparently reduced by pretreatment with adrenaline, timolol and pilocarpine. (Noradrenaline concentrations were 0.599 +/- 0.239 ng/ml in glaucoma, and 0.970 +/- 0.445 ng/ml in cataract patients.) Dopamine was found in two of six cataract patients (0.123 and 0.318 ng/ml), and in all the glaucoma group (0.221 +/- 0.170 ng/ml). Plasma noradrenaline concentration was probably increased in glaucoma, when compared to the cataract patients. These results confirm our findings in the non-human primate, and suggest that adrenaline may act, at least in part, by causing denervation or inhibition of noradrenaline release in the anterior segment of the eye, and probably by release of dopamine into the aqueous humour. The unexplained and new finding of dopamine in the aqueous humour may have some bearing on the action of dopaminergic drugs for the treatment of glaucoma. Future treatment of ocular hypertension may rely more on sympathetic denervation than on conventional adrenergic therapy.


Evaluation of DILI Predictive Hypotheses in Early Drug Development.
Drug-induced liver injury (DILI) is a leading cause of drug failure in clinical trials and a major reason for drug withdrawals. DILI has been shown to be dependent on both daily dose and extent of hepatic metabolism. Yet, early in drug development daily dose is unknown. Here, we perform a comprehensive analysis of the published hypotheses that attempt to predict DILI, including a new analysis of the Biopharmaceutics Drug Disposition Classification System (BDDCS) in evaluating the severity of DILI warnings in drug labels approved by the FDA and the withdrawal status due to adverse drug reactions (ADRs). Our analysis confirms that higher doses ≥50 mg/day lead to increased DILI potential, but this property alone is not sufficient to predict the DILI potential. We evaluate prior attempts to categorize DILI such as Rule of 2, BSEP inhibition, and measures of key mechanisms of toxicity compared to BDDCS classification. Our results show that BDDCS Class 2 drugs exhibit the highest DILI severity and that all of the published methodologies evaluated here, except when daily dose is known, do not yield markedly better predictions than BDDCS. The assertion that extensive metabolized compounds are at higher risk of developing DILI is confirmed but can be enhanced by differentiating BDDCS Class 2 from Class 1 drugs. We do not propose that the BDDCS classification, which does not require knowledge of the clinical dose, is sufficiently predictive/accurate of DILI potential for new molecular entities but suggest that comparison of proposed DILI prediction methodologies with BDDCS classification is a useful tool to evaluate the potential reliability of newly proposed algorithms. The most successful approaches to predict DILI potential all include a measure of dose, yet there is a quantifiable uncertainty associated with the predicted dose early in drug development. Here, we compare the possibility of predicting DILI potential using the BDDCS classification versus previously published methods and note that many hypothesized predictive DILI metrics do no better than just avoiding BDDCS Class 2 drugs.


Doubly robust estimator for net survival rate in analyses of cancer registry data.
Cancer population studies based on cancer registry databases are widely conducted to address various research questions. In general, cancer registry databases do not collect information on cause of death. The net survival rate is defined as the survival rate if a subject would not die for any causes other than cancer. This counterfactual concept is widely used for the analyses of cancer registry data. Perme, Stare, and Estève (2012) proposed a nonparametric estimator of the net survival rate under the assumption that the censoring time is independent of the survival time and covariates. Kodre and Perme (2013) proposed an inverse weighting estimator for the net survival rate under the covariate-dependent censoring. An alternative approach to estimating the net survival rate under covariate-dependent censoring is to apply a regression model for the conditional net survival rate given covariates. In this article, we propose a new estimator for the net survival rate. The proposed estimator is shown to be doubly robust in the sense that it is consistent at least one of the regression models for survival time and for censoring time. We examine the theoretical and empirical properties of our proposed estimator by asymptotic theory and simulation studies. We also apply the proposed method to cancer registry data for gastric cancer patients in Osaka, Japan.


Stability of rubella complement-fixing antigens.
Various types of rubella complement-fixing (CF) antigen preparations derived from infected BHK-21 cell cultures were examined for stability to certain chemical and physical agents. Antigens studied included: infected culture fluids concentrated 100-fold, ether-treated fluid concentrates, alkaline buffer extracts of infected cells, and large- and small-particle CF antigens separated by Sephadex gel filtration. All preparations were stable at -20 C for months, and were unaffected by three cycles of freezing and thawing. Ether treatment rendered antigens highly susceptible to thermal inactivation at 56 C; untreated antigens were inactivated slowly and showed a persistent fraction of activity even after 2 hr. Large-particle antigen was found to be slightly more susceptible than small-particle antigen to thermal inactivation and ether treatment. CF activity in alkaline buffer extracts was more labile than that in untreated or ether-treated fluid concentrates upon dialysis, Sephadex gel filtration, and sucrose density gradient centrifugation.


Fine-grained identification of camera devices based on inherent features.
Camera devices are being deployed everywhere. Cities, enterprises, and more and more smart homes are using camera devices. Fine-grained identification of devices brings an in-depth understanding of the characteristics of these devices. Identifying the device type helps secure the device safe. But, existing device identification methods have difficulty in distinguishing fine-grained types of devices. To address this challenge, we propose a fine-grained identification method based on the camera deviceso inherent features. First, feature selection is based on the coverage and differences of the inherent features type. Second, the features are classified according to their representation. A design feature similarity calculation strategy (FSCS) for each type of feature is established. Then the feature weights are determined based on feature entropy. Finally, we present a device similarity model based on the FSCS and feature weights. And we use this model to identify the fine-grained type of a target device. We have evaluated our method on Dahua and Hikvision camera devices. The experimental results show that we can identify the deviceos fine-grained type when some inherent feature values are missing. Even when the inherent feature pmissing rateq is 50%, the average accuracy still exceeds 80%.


Mechanistic aspects of IPTG (isopropylthio-β-galactoside) transport across the cytoplasmic membrane of Escherichia coli-a rate limiting step in the induction of recombinant protein expression.
Coupling transcription of a cloned gene to the lac operon with induction by isopropylthio-β-galactoside (IPTG) has been a favoured approach for recombinant protein expression using Escherichia coli as a heterologous host for more than six decades. Despite a wealth of experimental data gleaned over this period, a quantitative relationship between extracellular IPTG concentration and consequent levels of recombinant protein expression remains surprisingly elusive across a broad spectrum of experimental conditions. This is because gene expression under lac operon regulation is tightly correlated with intracellular IPTG concentration due to allosteric regulation of the lac repressor protein (lacY). An in-silico mathematical model established that uptake of IPTG across the cytoplasmic membrane of E. coli by simple diffusion was negligible. Conversely, lacY mediated active transport was a rapid process, taking only some seconds for internal and external IPTG concentrations to equalize. Optimizing kcat and KM parameters by targeted mutation of the galactoside binding site in lacY could be a future strategy to improve the performance of recombinant protein expression. For example, if kcat were reduced whilst KM was increased, active transport of IPTG across the cytoplasmic membrane would be reduced, thereby lessening the metabolic burden on the cell and expediating accumulation of recombinant protein. The computational model described herein is made freely available and is amenable to optimize recombinant protein expression in other heterologous hosts. A computational model made freely available to optimize recombinant protein expression in Escherichia coli other heterologous hosts.


A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer's Disease.
Alzheimer's disease (AD) is the most common neurodegenerative disease illustrated by neuronal dysfunctions, leading to memory weaknesses and personality changes mostly in the aged population worldwide. The exact cause of AD is unclear, but numerous studies have addressed the involvement of oxidative stress (OS), induced by reactive oxygen species (ROS), to be one of the leading causes in developing AD. OS dysregulates the cellular homeostasis, causing abnormal protein and lipid metabolism. Nutrition plays a pivotal role in modulating the antioxidant system and decreases the neuronal ROS level, thus playing an important therapeutic role in neurodegenerative diseases, especially in AD. Hence, medicinal herbs and their extracts have received global attention as a commercial source of antioxidants Lupeol. Lupeol is a pentacyclic triterpenoid and has many biological functions. It is available in fruits, vegetables, and medicinal plants. It has shown effective antioxidant and anti-inflammatory properties, and higher blood-brain barrier permeability. Also, the binding and inhibitory potentials of Lupeol have been investigated and proved to be effective against certain receptor proteins and enzymes in AD studies by computational molecular docking approaches. Therefore, AD-related research has gained interest in investigating the therapeutic effects of Lupeol. However, despite its beneficial effects in AD, there is still a lack of research in Lupeol. Hence, we compiled in this analysis all preclinical research that looked at Lupeol as an antioxidant and anti-inflammatory agent for AD.


Presence of a specific immune complex in the cell-free ascites of a spontaneously metastasizing rat mammary adenocarcinoma, TMT-081.
We have previously reported that a mammary tissue-specific antigen (MTA) occurs in the circulation of rats bearing the metastatic mammary tumor, TMT-081. In this communication we present immunochemical evidence that MTA also exists in the form of a soluble immune complex in the sera and ascites of TMT-081-bearing rats. This immune complex, however, has no effect on the growth of TMT-081 in rats. Neither the MTA nor the immune complex could be detected in the circulation of lactating rats or rats bearing the nonmetastatic mammary tumor, MT-100. Thus, it appears that the spontaneously metastasizing tumor, TMT-100, considered previously to be nonimmunogenic or weakly immunogenic by conventional tests, does in fact elicit an apparently ineffective humoral response as manifested by the formation of an immune complex containing MTA.


An outbreak of syphilis in Oslo.
During 1999 and 2000, an outbreak of syphilis occurred in Norway: 93 cases were reported to the National Institute of Public Health. This report summarizes a retrospective investigation of the medical records of 60 patients with primary, secondary and early latent syphilis treated during 1999-2000 at the Department of STD at the Ullevål University Hospital in Oslo. Five women and 55 men were treated, mean age 38.6 and 44.9 years, respectively. Of the 60 cases, 14 (23.3%) had primary, 39 (65.0) secondary and seven (11.7%) early latent syphilis. Men who have sex with men (MSM) constituted 78.2% (43/55) of the male patients. Transmission among MSM was related to casual sexual contacts in bathhouses in Oslo. Two cases occurred among men with previously diagnosed HIV infection. Two new cases of HIV were reported. Condom use was inconsistent, and seldom used for oral sex.


Dual-task walking over a compliant foam surface: A comparison of people with transfemoral amputation and controls.
People with lower limb amputation are unable to reliably sense ground characteristics due to compromised sensory inputs from the missing limb. As a result, they may rely on compensatory strategies, such as use of cognitive resources, when walking over complex surfaces. This study examined interactions between cognition and walking over a compliant surface in 14 people with transfemoral amputation (TFA) and 14 controls using a dual-task paradigm. Walking was assessed with quantitative motion analysis in both single-task (walking alone) and dual-task (walking while performing a cognitive task) conditions over a compliant foam surface. Outcomes were walking speed, step width, step time asymmetry, step time variability, and the speed and accuracy of cognitive task performance. For each outcome, effects of task (single-task, dual-task) and group (TFA, control) were examined with repeated-measures analysis of variance. No significant group-by-task interactions were observed for cognitive task performance. A significant group-by-task interaction for step time asymmetry indicated that participants with TFA increased temporal asymmetry in dual-task relative to single-task conditions, while control participants maintained symmetrical gait. The addition of a concurrent cognitive task did not differentially affect other aspects of gait between groups. Significant main effects of group for all walking outcomes indicated that participants with TFA walked slower, with wider, more asymmetric, and more variable steps than controls. Results suggest that gait quality degrades in challenging dual-task conditions for people with TFA, but not controls, consistent with the idea that people with TFA may use increased cognitive resources to control walking in complex environments.


Pharmacological Approaches for Treatment-resistant Bipolar Disorder.
Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature mortality. Treatment responses typically are incomplete, especially for depressive components, so that many cases can be considered "treatment resistant." We reviewed reports on experimental treatments for such patients: there is a striking paucity of such research, mainly involving small incompletely controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need for more systematic, simpler, and better controlled studies in more homogeneous samples of patients.


The ASC/SIL ratio for cytopathologists as a quality control measure: a follow-up study.
Monitoring the relative frequency of the interpretations of atypical squamous cells (ASC) and squamous intraepithelial lesions (SIL) has been proposed as a quality control measure. To assess its value, an ASC/SIL ratio was calculated every 6 months for 3.5 years, and confidential feedback was provided to 10 cytopathologists (CPs). By using simple regression analysis, we analyzed the initial and final ASC/SIL ratios for individual CPs and for the entire group. The ratio was below the upper benchmark of 3:1 for all but 1 CP during every 6-month period. The ratio for all CPs combined showed a downward trend (from 2.05 to 1.73). The ratio for 6 CPs decreased, and for two of them the decrease was statistically significant. One CP showed a statistically significant increase in the ASC/SIL ratio. The decrease for some CPs likely reflects the salutary effect of confidential feedback and counseling.


Coadministration of alloxan and nicotinamide in rats produces biochemical changes in blood and pathological alterations comparable to the changes in type II diabetes mellitus.
In the present study, thirty six male Sprague Dawley rats were randomly divided into six groups and were injected with varying doses of alloxan (Ax) and nicotinamide (NA). The serum levels of glucose, insulin, and adiponectin were measured weekly up to 4 weeks. Elevated levels of glucose were observed in all groups on days 7, 14, 21, and 28, except in groups a and f (control). The serum insulin levels were significantly elevated in groups b and c on day 7, when compared with that in group f, whereas a decrease in the serum insulin levels was observed in groups d and e on days 21 and 28. The adiponectin levels showed inconsistencies on days 7 and 14. However, significant decrease in the adiponectin levels was observed on days 21 and 28. Histological section of the pancreas showed mild (group a), moderate (group b) to severe (groups c, d, and e) degenerative changes. Concomitant fatty changes in the liver and inflammatory infiltration of the kidney were markedly observed in all the treated groups, when compared to control. These results suggested that the use of selective combination of Ax120 + NA50 injection demonstrated type II diabetes mellitus in rats.


Protein folding at the membrane interface, the structure of Nogo-66 requires interactions with a phosphocholine surface.
Repair of damage to the central nervous system (CNS) is inhibited by the presence of myelin proteins that prevent axonal regrowth. Consequently, growth inhibitors and their common receptor have been identified as targets in the treatment of injury to the CNS. Here we describe the structure of the extracellular domain of the neurite outgrowth inhibitor (Nogo) in a membrane-like environment. Isoforms of Nogo are expressed with a common C terminus containing two transmembrane (TM) helices. The ectodomain between the two TM helices, Nogo-66, is active in preventing axonal growth [GrandPre T, Nakamura F, Vartanian T, Strittmatter SM (2000) Nature 403:439-444]. We studied the structure of Nogo-66 alone and in the presence of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles and dodecylphosphocholine (DPC) micelles as membrane mimetics. We find that Nogo-66 is largely disordered when free in solution. However, when bound to a phosphocholine surface Nogo-66 adopts a unique, stable fold, even in the absence of TM anchors. Using paramagnetic probes and protein-DPC nuclear Overhauser effects (NOEs), we define portions of the growth inhibitor likely to be accessible on the cell surface. With these data we predict that residues (28-58) are available to bind the Nogo receptor, which is entirely consistent with functional assays. Moreover, the conformations and relative positions of side chains recognized by the receptor are now defined and provide a foundation for antagonist design.


[Development of A synthetic positive control for the nucleic acid detection of mumps virus].
To rapidly identify the cross-contamination problems caused by the positive control in the process of mumps virus nucleic acid detection, a new mumps virus RNA positive control was developed in this study. Using the same primers and reaction conditions, the cross-contamination problems caused by the positive control could be readily identified by comparing the fragments lengths of the PCR products between the positive control and the samples. This new RNA positive control of mumps virus can be widely used in the diagnosis and genotyping of mumps virus as a better laboratory quality control.


Calcitonin gene-related peptide containing sensory neurons innervating tooth pulp and buccal mucosa of the rat: an immunohistochemical analysis.
Differential peptidergic innervation of the rat buccal mucosa and incisor tooth pulp was demonstrated by experimental immunohistochemistry. In the buccal mucosa, calcitonin gene-related peptide (CGRP)-like immunoreactive (IR) nerve fibres were observed in both the epithelium and submucosal layer. Most of these fibres were also immunoreactive to substance P (SP). On the other hand, SP-IR fibres were less numerous than CGRP-IR fibres in the incisor tooth pulp. Fast blue (FB) was applied to the buccal mucosa and the incisor pulp chamber. Small (less than 20 microns) FB-labelled CGRP-IR neurons were more numerous in the buccal mucosa group, while medium to large neurons (20-50 microns) predominated in the incisor pulp. Following neonatal capsaicin treatment, CGRP- and SP-containing fibres in the buccal mucosa almost totally disappeared, but many CGRP-IR fibres remained in the incisor tooth pulp. The findings suggest that these two oral tissues are innervated by different subgroups of CGRP-IR neurons in the trigeminal ganglia.


Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor.
Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.


Correlation between postpartum depression and premenstrual dysphoric disorder: Single center study.
To describe the prevalence and correlates of the postpartum depression and premenstrual dysphoric disorder. One hundred sixty six women were assessed around 10th to 14th days after delivery in Gangneung Asan Hospital, Korea, from September 2011 to March 2012. We checked their risk factors for postpartum depressive disorders using the Beck Depression Inventory and the Edinburgh Postnatal Depression Scale. Premenstrual dysphoric disorder was evaluated retrospectively and was defined as having more than 5 of the following 10 symptoms: breast tenderness, bloating, headache, peripheral edema (hand and foot), depressive symptoms, anger, irritability, anxiety, oversensitivity, and exaggerated mood swings. The prevalence rate of postpartum depression using the Edinburgh Postnatal Depression Scale ≥10 and Beck Depression Inventory ≥10 was 13.9% (23/166). We found statistical differences (P<0.01) between the postpartum depression group and the postpartum non-depression group in smoking history, past history of psychiatric problems, and level of marital satisfaction. The prevalence rate of premenstrual syndrome (PMS) was 9% (15/166) and among 23 women in the postpartum depression group, eight were determined to have premenstrual dysphoric disorder, yielding a prevalence rate of 34.8% (8/23). Among 143 women in the postpartum non-depression group, seven were determined to have PMS, yielding a prevalence rate of 4.9% (7/143). A correlation between postpartum depression and PMS was thus found (P<0.01). PMS appears to be associated with postpartum depression. This means that a hormone-related etiology appears to be one risk factor for postpartum depression.


Interferometric measurement of arbitrary propagating vector beams that are tightly focused.
In this work, we demonstrate a simple setup to generate and measure arbitrary vector beams that are tightly focused. The vector beams are created with a spatial light modulator and focused with a microscope objective with an effective numerical aperture of 1.2. The transverse polarization components (Ex, Ey) of the tightly focused vector beams are measured with three-step interferometry. The axial component Ez is reconstructed using the transverse fields with Gauss's law. We measure beams with the following polarization states: circular, radial, azimuthal, spiral, flower, and spider web.


Study of sampling rate influence on neutron-gamma discrimination with stilbene coupled to a silicon photomultiplier.
Choosing a digitizer with an appropriate sampling rate is often a trade-off between performance and economy. The influence of sampling rates on the neutron-gamma Pulse Shape Discrimination (PSD) with a solid stilbene scintillator coupled to a Silicon Photomultiplier was investigated in this work. Sampling rates from 125MSPS to 2GSPS from a 10-bit digitizer were used to collect detector pulses produced by the interactions of a Cf-252 source. Due to the decreased signal-to-noise ratio (SNR), the PSD performance degraded with reduced sampling rates. The reason of PSD performance degradation was discussed. Then, an efficient combination of filtering and digital signal processing (DSP) was then applied to suppress the timing noise and electronic background noise. The results demonstrate an improved PSD performance especially at low sampling rates, down to 125MSPS. Using filtering and DSP, the ascribed Figure of Merit (FOM) at 125keVee (± 10keVee) increased from 0.95 to 1.02 at 125MSPS. At 300keVee and above, all the FOMs are better than 2.00. Our study suggests that 250MSPS is a good enough sampling rate for neutron-gamma discrimination in this system in order to be sensitive to neutrons at and above ~ 125keVee.


Re-evaluation of antitumor effects of combination chemotherapy with interferon-alpha and 5-fluorouracil for advanced hepatocellular carcinoma.
To evaluate the efficacy of combination chemotherapy with interferon-alpha (IFNalpha) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC). Twenty-eight HCC patients in advanced stage were enrolled in the study. They were treated with IFNalpha/5-FU combination chemotherapy. One cycle of therapy lasted for 4 wk. IFNalpha (3 x 10(6) units) was subcutaneously injected thrice weekly on days 1, 3, and 5 for 3 wk, and 5-FU (500 mg/d) was administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. No drugs were administered during the 4(th) wk. The effect of combination chemotherapy was evaluated in each patient after every cycle based on the reduction of tumor volume. After the 1(st) cycle of therapy, 16 patients showed a partial response (PR, 57.1%) but none showed a complete response (CR, 0%). At the end of therapy, the number of patients who showed a CR, PR, or no response (NR) was 1, 10, and 17, respectively. The response rate for therapy (CR+PR) was 21.5%. Biochemical tests before therapy were compared between responsive (CR+PR) and non-responsive (NR) patients, but no significant differences were found for any of the parameters examined, indicating that no reasonable predictors could be identified in our analysis. Attempts should be made to discriminate between responders and non-responders by evaluating tumor size after the first cycle of IFNalpha/5-FU combination chemotherapy. For non-responders, therapy should not proceed to the next cycle, and instead, different combination of anticancer drugs should be explored.


Phytochemical investigations and antioxidant potential of roots of Leea macrophylla (Roxb.).
Oleanolic acid (NZ-15), 7 α, 28-olean diol (NZ-38) and Stigmasterol (NZ-14) were isolated from the ethanolic extracts of the roots of Leea macrophylla (Family: Leeaceae) by using chromatographic analysis. This is the first report of isolation of these compounds from this plant. Their structures were constructed by spectroscopic analysis and by comparing the data with the published one. Subsequently the ethanolic extract was fractionated with two organic solvents and all the fractions were studied to evaluate their in vitro antioxidant property. The ethanolic extract was fractionated with two organic solvents and all the fractions were studied to evaluate their in vitro antioxidant property by DPPH free radical scavenging assay, superoxide anion radical scavenging assay, nitric oxide radical scavenging assay, and reducing power assay. In the DPPH free radical scavenging assay and superoxide radical scavenging assay, the ethyl acetate soluble fraction of ethanolic extract revealed the highest free radical scavenging activity with IC50 value of 2.65 and 155.62 μg/ml, respectively as compared to standard ascorbic acid (IC50 value of 5.8 and 99.66 μg/ml). Ethyl acetate fraction also possessed highest reducing power activity with an EC50 value of 15.27 μg/ml compared to ascorbic acid (EC50 0.91 μg/ml). On the other hand, the carbon tetrachloride fraction exhibited most significant NO scavenging activity with IC50 value of 277.8 μg/ml that was even higher than that of standard ascorbic acid (IC50 value 356.04 μg/ml). In addition, the total phenolic contents of these extract and fractions were evaluated using Folin-Ciocalteu reagent and varied from 7.93 to 50.21 mg/g dry weight expressed as gallic acid equivalents (GAE). This study showed that different extracts of roots of L. macrophylla possess potential DPPH, superoxide, and NO free radical scavenging activities. The antioxidant activities of the plant extracts might be due to the presence of oleanolic acid, oleanolic acid derivative 7 α, 28-olean diol and stigmasterol.


Structure of the B880 holochrome of Rhodospirillum rubrum as studied by the radiation inactivation method.
Chromatophores from photoreaction centerless strain F24 of Rhodospirillum rubrum were subjected to different doses of gamma radiation. Target theory was applied to the induced decay of the B880 holochrome pigments as analyzed by absorption spectroscopy of the membranes and of organic solvent extracts. Destruction of bacteriochlorophyll is associated with a target size of 7 kDa. This indicates that each one of the two different 6-kDa holochrome polypeptides binds one molecule of this pigment. The target size of spirilloxanthin, 12 kDa, suggests that both polypeptides contribute to the binding site of this carotenoid. The 880 nm absorption band and the oxidation-induced 1225 nm band have a target size of 14 kDA. Therefore, these bands are due to interaction between two bacteriochlorophyll molecules, each one of which resides on a different polypeptide. This 14-kDa complex decays into a bacteriochlorophyll monomer associated with a target size of 7 kDa. The absolute absorption spectra of the protein-bound bacteriochlorophyll pair and monomer are presented.


Preventive effect of N-acetylcysteine in a mouse model of steroid resistant acute exacerbation of asthma.
Oxidative stress appears to have an important role in glucocorticoid insensitivity, as a crucial problem in asthma therapy. We studied the preventive effect of antioxidant N-acetylcysteine (NAC) on the airway hyper-responsiveness (AHR) and the accumulation of inflammatory cells in the airways in an animal model of steroid resistant acute exacerbation of asthma. Systemically sensitized Balb/C mice were exposed to Ovalbumin aerosol on days 13, 14, 15 and 16, followed by intratracheal lipopolysaccharide (LPS) to induce acute exacerbation. NAC (intraperitoneal, 320 mg/kg 30 min before and 12 hours after each challenge) reduced hyper-responsiveness with/out dexamethasone. LPS application caused neutrophilia in bronchoalveolar lavage fluid (BALF) and eosinophil count was higher than respective control in BALF as well as neutrophils after dexamethasone treatment. NAC significantly decreased neutrophil and eosinophil count in BALF as well as inflammatory cytokines (IL-13 and IL-5).We concluded that addition of NAC to asthma therapy has beneficial preventive effects in an animal model of steroid resistant acute exacerbation of asthma.


Effects of neonatal administration of monosodium glutamate on somatotrophs and growth hormone secretion in prepubertal male and female rats.
Female and male rats were injected with monosodium L-glutamate (MSG; 4 mg/g BW) or 0.9% saline as neonates and then decapitated on days 35 and 40 of life, respectively. Trunk blood was collected for RIA of serum GH. Anterior pituitary glands (APGs) were bisected. One half was assayed for GH. The other half was placed in culture medium to study the basal GH release rate. Pituitary sections from additional rats were stained for GH, and morphometric analyses were performed on the GH cells. Treatment with MSG lowered serum GH levels and gland GH content in female but not in male rats. MSG did not alter the gland GH concentration or the basal GH release rate whether expressed per mg APG or per entire gland in either sex. The mean cross-sectional area of GH cells was reduced in either sex of MSG-treated rats. The numerical density of GH cells and the percentage of GH cells in APGs were similar in saline- and MSG-treated rats of either sex. The volume density of GH cells was lower in MSG-treated male rats only. The results suggest that in prepubertal rats which had been given MSG as neonates there is a sex difference in mean serum GH concentration and APG GH content, GH cell size is reduced in both sexes, and the individual GH cells contain normal amounts of GH in spite of their smaller size.


[Cardiorespiratory arrest in children with trauma].
To analyze the characteristics and outcome of cardiorespiratory arrest secondary to trauma in children. We performed a secondary analysis of data from a prospective, multicenter study of cardiorespiratory arrest in children. Data were recorded according to the Utstein style. Twenty-eight children (age range: 7 days to 16 years) with cardiorespiratory arrest secondary to trauma were evaluated. The outcome variables were return of spontaneous circulation, sustained (more than 20 minutes) return of spontaneous circulation (initial survival), and survival at hospital discharge (final survival) in relation to the characteristics of the cardiorespiratory arrest and cardiopulmonary resuscitation. Neurological and general performance outcome was assessed by means of the Pediatric Cerebral Performance Category scale and the Pediatric Overall Performance Category scale. Return of spontaneous circulation was obtained in 18 patients (64.2 %), initial survival was achieved in 14 (50 %) and final survival was achieved in three (10.7 %) (two without neurological sequelae and one with vegetative status). Final survival was significantly higher in patients with respiratory arrest (33.3 %) than in those with cardiac arrest (4.5 %), p = 0.04. Final survival was also higher in patients with a duration of cardiopulmonary resuscitation shorter than 20 minutes (27.2 %) than in the remaining patients (0 %), p =0.05. The two survivors without neurologic sequelae had respiratory arrest. Survival until hospital discharge in children with cardiorespiratory arrest secondary to trauma is lower than that in children with cardiorespiratory arrest. Patients with respiratory arrest when resuscitation is started and those with a duration of cardiopulmonary resuscitation of less than 20 minutes showed better survival than the remaining patients.


Use of vascularised free fibula in limb reconstruction (for non-malignant defects).
The case series was conducted at the Department of Plastic Surgery, Combined Military Hospital, Rawalpindi, from June 2009 to May 2011, and comprised 19 patients in whom free fibula flap was performed for upper and lower limb reconstruction, using SPSS 16. Results showed that flap survival was 100%. One (5.2%) flap was re-explored for venous congestion and was salvaged. One (5.2%) patient of congenital pseudoarthrosis of tibia had a fracture of the fibula and was treated with external fixation. Average follow up was 8 months. Mean union time and full weight-bearing was 6.5 +/- 1.34 months (range 3-8 months) and 9 months, respectively. No recurrence of pseudoathrosis was observed until the last follow up, with only a 1.5 cm length discrepancy in one patient. The results proved that a microvascular free fibular flap heals rapidly, causes early functional recovery and it can be raised as an osteocutaneous flap.


Haemodynamic and metabolic adaptations in coronary microvascular disease.
We aimed to evaluate the microcirculatory resistance (MR) and myocardial metabolic adaptations at rest and in response to increased cardiac workload in patients with suspected coronary microvascular dysfunction (CMD). Patients with objective ischaemia and/or myocardial injury and non-obstructive coronary artery disease underwent thermodilution-derived microcirculatory assessment and transcardiac blood sampling during graded exercise with adenosine-mediated hyperaemia. We measured MR at rest and following supine cycle ergometry. Patients (n=24) were stratified by the resting index of MR (IMR) into normal-IMR (IMR<22U, n=12) and high-IMR groups (IMR≥22U, n=12). The mean age was 57 years; 67% were males and 38% had hypertension. The normal-IMR group had increased IMR response to exercise (16±5 vs 23±12U, p=0.03) compared with the high-IMR group, who had persistently elevated IMR at rest and following exercise (38±19 vs 33±15U, p=0.39) despite similar exercise duration and rate-pressure product between the groups, both p>0.05. The normal-IMR group had augmented oxygen extraction ratio following exercise (53±18 vs 64±11%, p=0.03) compared with the high-IMR group (65±14 vs 59±11%, p=0.26). The postexercise lactate uptake was greater in the high-IMR (0.04±0.05 vs 0.11±0.07 mmol/L, p=0.004) compared with normal-IMR group (0.08±0.06 vs 0.09±0.09 mmol/L, p=0.67). The high-IMR group demonstrated greater troponin release following exercise compared with the normal-IMR group (0.13±0.12 vs 0.001±0.05 ng/L, p=0.03). Patients with suspected CMD appear to have distinctive microcirculatory resistive and myocardial metabolic profiles at rest and in response to exercise. These differences in phenotypes may permit individualised therapies targeting microvascular responsiveness (normal-IMR group) and/or myocardial metabolic adaptations (normal-IMR and high-IMR groups).


Tailoring nanoscopic confines to maximize catalytic activity of hydronium ions.
Acid catalysis by hydronium ions is ubiquitous in aqueous-phase organic reactions. Here we show that hydronium ion catalysis, exemplified by intramolecular dehydration of cyclohexanol, is markedly influenced by steric constraints, yielding turnover rates that increase by up to two orders of magnitude in tight confines relative to an aqueous solution of a Brønsted acid. The higher activities in zeolites BEA and FAU than in water are caused by more positive activation entropies that more than offset higher activation enthalpies. The higher activity in zeolite MFI with pores smaller than BEA and FAU is caused by a lower activation enthalpy in the tighter confines that more than offsets a less positive activation entropy. Molecularly sized pores significantly enhance the association between hydronium ions and alcohols in a steric environment resembling the constraints in pockets of enzymes stabilizing active sites.