Bottom-up and middle-out approaches to electronic patient information systems: a focus on healthcare pathways.
A study is reported that examines the use of electronic health record (EHR) systems in two UK local health communities. These systems were developed locally and the aim of the study was to explore how well they were supporting the coordination of care along healthcare pathways that cross the organisational boundaries between the agencies delivering health care. The paper presents the findings for two healthcare pathways; the Stroke Pathway and a pathway for the care of the frail elderly in their own homes. All the pathways examined involved multiple agencies and many locally tailored EHR systems are in use to aid the coordination of care. However, the ability to share electronic patient information along the pathways was patchy. The development of systems that did enable effective sharing of information was characterised by sociotechnical system development, i.e. associating the technical development with process changes and organisational changes, with local development teams that drew on all the relevant agencies in the local health community and on evolutionary development, as experience grew of the benefits that EHR systems could deliver. The study concludes that whilst there may be a role for a national IT strategy, for example, to set standards for systems procurement that facilitate data interchange, most systems development work needs to be done at a 'middle-out' level in the local health community, where joint planning between healthcare agencies can occur, and at the local healthcare pathway level where systems can be matched to specific needs for information sharing.


Periodicity Pitch Perception.
This study presents a computational model to reproduce the biological dynamics of "listening to music." A biologically plausible model of periodicity pitch detection is proposed and simulated. Periodicity pitch is computed across a range of the auditory spectrum. Periodicity pitch is detected from subsets of activated auditory nerve fibers (ANFs). These activate connected model octopus cells, which trigger model neurons detecting onsets and offsets; thence model interval-tuned neurons are innervated at the right interval times; and finally, a set of common interval-detecting neurons indicate pitch. Octopus cells rhythmically spike with the pitch periodicity of the sound. Batteries of interval-tuned neurons stopwatch-like measure the inter-spike intervals of the octopus cells by coding interval durations as first spike latencies (FSLs). The FSL-triggered spikes synchronously coincide through a monolayer spiking neural network at the corresponding receiver pitch neurons.


Witnessing Quality of Life of Persons with Profound Intellectual and Multiple Disabilities. A practical-Philosophical Approach.
Persons with profound intellectual and multiple disabilities (PIMD) cannot speak about their Quality of Life (QoL), which makes it necessary to involve others. In current approaches, these 'others' are seen as assessors trying to describe QoL as objectively as possible, which involves a reduction of their experiences, through which they develop knowledge on the QoL of the person with PIMD. The objective of this paper is to give caregivers' knowledge on the QoL of a person with PIMD a theoretical basis that values these experiences. We will argue that caregivers should be seen as witnesses, not assessors, and their statements on QoL as testimonies, not assessments. Audiences judge the trustworthiness of these witnesses intersubjectively, which implies a relationship characterized by trust and suspicion. Trust supports the witness to tell in her own words about the QoL of the person with PIMD; it demands receptivity, indicating that both the witness and the audience are willing to reconsider their perspective on QoL. Suspicion is necessary too, which helps the witness to critically approach her own interpretations and supports her to create more trustworthy testimonies. We conclude that the concept of witnessing helps to acknowledge caregivers' experiential knowledge of QoL of a person with PIMD, which may also apply to other persons who cannot speak about their own QoL. We hope that our study will empower caregivers to give testimonies on QoL of a person with PIMD, which is crucial when complex decisions about the life of this person have to be made.


Biochemical and Hematologic Reference Intervals for Aged Xenopus laevis in a Research Colony.
Xenopus laevis, the African clawed frog, is commonly used in developmental and toxicology research studies. Little information is available on aged X. laevis; however, with the complete mapping of the genome and the availability of transgenic animal models, the number of aged animals in research colonies is increasing. The goals of this study were to obtain biochemical and hematologic parameters to establish reference intervals for aged X. laevis and to compare results with those from young adult X. laevis. Blood samples were collected from laboratory reared, female frogs (n = 52) between the ages of 10 and 14 y. Reference intervals were generated for 30 biochemistry analytes and full hematologic analysis; these data were compared with prior results for young X. laevis from the same vendor. Parameters that were significantly higher in aged compared with young frogs included calcium, calcium:phosphorus ratio, total protein, albumin, HDL, amylase, potassium, CO2, and uric acid. Parameters found to be significantly lower in aged frogs included glucose, AST, ALT, cholesterol, BUN, BUN:creatinine ratio, phosphorus, triglycerides, LDL, lipase, sodium, chloride, sodium:potassium ratio, and anion gap. Hematology data did not differ between young and old frogs. These findings indicate that chemistry reference intervals for young X. laevis may be inappropriate for use with aged frogs.


Investigation of stable germane structures under high-pressure.
The evolutionary structure-searching method discovers that the energetically preferred compounds of germane can be synthesized at a pressure of 190 GPa. New structures with the space groups Ama2 and C2/c proposed here contain semimolecular H2 and V-type H3 units, respectively. Electronic structure analysis shows the metallic character and charge transfer from Ge to H. The conductivity of the two structures originates from the electrons around the hydrogen atoms. Further electron-phonon coupling calculations predict that the two phases are superconductors with a high Tc of 47-57 K for Ama2 at 250 GPa and 70-84 K for C2/c at 500 GPa from quasi-harmonic approximation calculations, which may be higher than under actual conditions.


Idiopathic recurrent acute pericarditis: familial Mediterranean fever mutations and disease evolution in a large cohort of Caucasian patients.
Idiopathic recurrent acute pericarditis (IRAP) is suspected to be an autoimmune phenomenon. We studied 46 consecutive patients. We looked for: 1) the occurrence of new diagnoses of autoimmune diseases during our follow up; 2) HLA typing; and 3) the presence of the most frequent mutations linked to familial Mediterranean fever (FMF gene or MEFV). HLA typing was done in 21 patients at loci B, DRB1, DQA1 and DQB1. MEFV gene was looked in 23 patients using specific primers. During the follow-up we made a new diagnosis of primary Sjögren's syndrome in four patients (8.7%) and of rheumatoid arthritis in one patient (2.2%). HLA B14, DRB1*01 and DQB1*0202 were significantly more prevalent, but we did not find a typical HLA typing. MEFV gene was searched: exon 10 was checked by sequence and the E148Q mutation by restriction site analysis. No mutations were found. In conclusion, the prevalence of definite immunorheumatological diseases and the absence of the mutations linked to FMF reinforce the notion that idiopathic acute recurrent pericarditis is an autoimmune condition.


Thermomechanical analysis of shape memory devices.
Shape memory alloys (SMA) are being increasingly used in various industrial applications as actuators, connectors, or damping materials. In the medical field, superelastic devices such as eyeglass frames, stents or guide catheters have come to market in the recent years. The design of SMA devices has usually been based on trial and error, since until recently no general simulation model was available to assist application engineers. The purpose of this article is to describe the computational methodology developed, validated and used for several industrial projects at Ecole Polytechnique of Montréal to simulate the thermomechanical behavior of shape memory materials. This new approach includes three main stages: experimental characterization, construction of a nonlinear material law based on dual kriging interpolation and finally, calculation of the thermomechanical response of SMA devices. For complex geometry, finite element analysis is used, but for simple devices such as springs or electrically activated SMA wires, simplified calculation methods are satisfactory. Validation results recently obtained will also be presented, and examples of industrial applications briefly reviewed.


[Serum iron and serum copper in patients with lymphogranulomatosis].
The serum iron and serum copper level was determined in fifteen patients with lymphogranulomatosis before and during the course of the therapy. While the serum copper was increased in all stages, for the serum iron only in the stages III and IV a tendency to diminution was found. With obtaining the remission a significant increase of the serum iron and a significant decrease of the serum copper developed. The normalization of serum iron and serum copper suggests a remission, the dissociation of the two parameters an activity of the lymphogranulomatosis.


Visible-Light-Driven Photocatalytic Coupling of Neat Benzylamine over a Bi-Ellagate Metal-Organic Framework.
Selective aerobic oxidation of benzylamine to N,N-benzylidenebenzylamine was achieved using a bismuth ellagate (Bi-ellagate) metal-organic framework (MOF) under simulated visible light irradiation. The bismuth ellagate photocatalyst was characterized using several spectroscopic techniques: powder X-ray diffraction (PXRD), diffuse reflectance spectroscopy (DRS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and nitrogen sorption measurements. Product formation was confirmed using 1H-NMR, 13C-NMR, and FTIR. The photocatalytic performance of Bi-ellagate was studied for the first time, which exhibits a band gap value of 2.62 eV, endowing it with a high photocatalytic activity under visible light irradiation. The reaction product, N,N-benzylidenebenzylamine, was selectively obtained with a high conversion yield of ∼96% under solvent-free conditions compared to other control experiments. The Bi-ellagate photocatalyst was recovered and reused four times without any significant loss in its activity, which provides an eco-friendly, low-cost, recyclable, and efficient photocatalyst for potential photocatalytic applications.


Translocation and biotransformation of CuO nanoparticles in rice (Oryza sativa L.) plants.
Metal-based nanoparticles (MNPs) may be translocated and biochemically modified in vivo, which may influence the fate of MNPs in the environment. Here, synchrotron-based techniques were used to investigate the behavior of CuO NPs in rice plants exposed to 100 mg/L CuO NPs for 14 days. Micro X-ray fluorescence (μ-XRF) and micro X-ray absorption near edge structure (μ-XANES) analysis revealed that CuO NPs moved into the root epidermis, exodermis, and cortex, and they ultimately reached the endodermis but could not easily pass the Casparian strip; however, the formation of lateral roots provided a potential pathway for MNPs to enter the stele. Moreover, bulk-XANES data showed that CuO NPs were transported from the roots to the leaves, and that Cu (II) combined with cysteine, citrate, and phosphate ligands and was even reduced to Cu (I). CuO NPs and Cu-citrate were observed in the root cells using soft X-ray scanning transmission microscopy (STXM).


[111In-antimyosin scintigraphy on acute myocardial infarction].
Indium-111 antimyosin (InAM) scintigraphy was performed in 17 patients with acute myocardial infarction (on 15 +/- 6 days from the onset). The degree of myocardial uptake was classified into 3 groups. They were ranged from low intensity as in bone marrow to high intensity as in liver. All of 17 cases showed positive myocardial uptake including low intensity. The locations of infarction judged by InAM were in agreement with those by electrocardiography, coronary angiography (CAG), and 99mTc-pyrophosphate scintigraphy (PYP, performed on 5 +/- 2 days from the onset). In 5 cases, the uptake of InAM showed doughnuts or diffuse pattern which was occasionally observed on PYP. These cases showed myocardial uptake of 4th degree of Parkey's classification with doughnuts-like pattern on PYP, and showed involvement of left anterior descending artery on CAG. In some cases, the extent of myocardial uptake on InAM did not agree with those on PYP.


Bile Duct Injuries as a Result of Cholecystectomy: An Australian Perspective.
Cholecystectomy remains the mainstay treatment for symptomatic gallstones. Despite the evolution of surgical techniques and approaches, bile duct injury represents a significant complication, even in experienced hands. It is associated with significant postoperative morbidity, resource utilisation and costs. Compared to the international data, there is a paucity of data on malpractice cases involving bile duct injuries (BDIs) proceeding to definitive judgment and defence. This article examines the surgical literature and the case law in Australia as it relates to BDIs following cholecystectomy. This article aims to discuss the issues surrounding major bile duct injury litigation and compares the Australian perspective with international experience.


Effect of hemodialysis on left ventricular systolic function in the presence and absence of beta-blockade: influence of left ventricular mass.
To assess the effect of hemodialysis on the left ventricular (LV) systolic function in the presence and absence of beta blockade, we performed echocardiography just prior to and immediately after 4-hour maintenance hemodialysis in 38 patients with end-stage renal disease. The LV systolic function was assessed in subgroups with normal and increased LV mass in both the beta blockade group (n = 19) and the non-beta blockade group (n = 19). There was a significant negative correlation between LV mass and the dialysis-induced change in the mean velocity of LV circumferential fiber shortening (mean Vcf) in both the beta blockade group (r = -0.93; p less than 0.0005) and in the non-beta blockade group (r = -0.82; p less than 0.0005). The mean dialysis-induced change in mean Vcf in the subgroup with increased LV mass in the beta blockade group (-0.02 +/- 0.11 circumferences/s) was significantly lower than the mean dialysis-induced change in mean Vcf in the non-beta blockade group (+0.12 +/- 0.04 circumferences/s; p less than 0.0005). Thus, the coexistence of increased LV mass and beta blockade significantly impedes the expected improvement of LV systolic function associated with hemodialysis.


Who takes responsibility for contraception, according to young Australian women?
Developments in reversible forms of female contraception are more advanced than developments in male contraception - which are still limited to the condom. These technological advancements have arguably shaped views around who should take responsibility for contraception. We investigate the notion that responsibility relates to gender-specific contraceptives. We aimed to explore young women's reports of contraceptive responsibility based on the last time they had sex, using demographic and free-text data from 1906 women who completed a longitudinal survey about contraceptive use. We analysed four patterns of responsibility: the woman took responsibility; the sexual partner took responsibility; both took responsibility; neither took responsibility. Our quantitative analyses found significant differences between the four groups on the following variables: contraceptive use at last sex, relationship status, ever been pregnant, parity, and medical consultations for contraception in the past six months. Our qualitative analysis identified distinct variability within and between the four patterns of responsibility in terms of contraceptive use and gender responsible. These findings challenge the gendered portrayal of contraceptive responsibility, in that women's responsibility is not necessarily tied to women-specific methods and vice versa. We encourage increased dialogue around contraceptive responsibility and decision-making in both clinical and educational settings.


Adult croup--a case report.
A case of a female adult patient with croup is described. Inflammation, as well as pseudomembranes, restricting the patency of trachea, developed within several hours after the first symptoms of infection were observed. Tracheostomy was performed Bronchofiberoscopies were repeated on a regular basis several times a day over a period of two weeks, with the removal of fibrinous casts and dense secretion being the only way to save the patient's life.


Predicting Obesity in Adults Using Machine Learning Techniques: An Analysis of Indonesian Basic Health Research 2018.
Obesity is strongly associated with multiple risk factors. It is significantly contributing to an increased risk of chronic disease morbidity and mortality worldwide. There are various challenges to better understand the association between risk factors and the occurrence of obesity. The traditional regression approach limits analysis to a small number of predictors and imposes assumptions of independence and linearity. Machine Learning (ML) methods are an alternative that provide information with a unique approach to the application stage of data analysis on obesity. This study aims to assess the ability of ML methods, namely Logistic Regression, Classification and Regression Trees (CART), and Naïve Bayes to identify the presence of obesity using publicly available health data, using a novel approach with sophisticated ML methods to predict obesity as an attempt to go beyond traditional prediction models, and to compare the performance of three different methods. Meanwhile, the main objective of this study is to establish a set of risk factors for obesity in adults among the available study variables. Furthermore, we address data imbalance using Synthetic Minority Oversampling Technique (SMOTE) to predict obesity status based on risk factors available in the dataset. This study indicates that the Logistic Regression method shows the highest performance. Nevertheless, kappa coefficients show only moderate concordance between predicted and measured obesity. Location, marital status, age groups, education, sweet drinks, fatty/oily foods, grilled foods, preserved foods, seasoning powders, soft/carbonated drinks, alcoholic drinks, mental emotional disorders, diagnosed hypertension, physical activity, smoking, and fruit and vegetables consumptions are significant in predicting obesity status in adults. Identifying these risk factors could inform health authorities in designing or modifying existing policies for better controlling chronic diseases especially in relation to risk factors associated with obesity. Moreover, applying ML methods on publicly available health data, such as Indonesian Basic Health Research (RISKESDAS) is a promising strategy to fill the gap for a more robust understanding of the associations of multiple risk factors in predicting health outcomes.


[Management of a foot deformity, caused by paralysis of the peroneal nerve, by transfer of the tendon of the posterior tibial muscle].
Author describes two cases: in the first, in consequence of a lesion of the deep peroneal nerve during operation, the development a paralytic drop foot, in the second, in consequence of a lesion of unknown etiology of the common peroneal nerve, paralytic club foot could be observed. In both cases the intraosseal transposition of the tendon of the posterior tibial muscle on the second cuneiform bone was performed with good result.


Percutaneous electrode guidance: a noninvasive technique for prelocation of peripheral nerves to facilitate peripheral plexus or nerve block.
Typically, peripheral nerve block is done by approximating nerve location, usually by use of anatomical landmarks. Precise nerve location has been done by needle exploration. A new method, percutaneous electrode guidance (PEG) of the block needle, was performed. A transcutaneous stimulating cylindrical electrode was used to indent the skin, locate the underlying nerve, and guide a block needle near it. PEG was used to prelocate the desired nerve or neural plexus by use of a shielded cylindrical electrode with a 1-mm-diameter conductive area of skin contact at the distal end, the center of which contained a 22-gauge (1/2 mm) hole, which precisely matched a shielded conventional block needle. Transcutaneous stimulation began at less than 10 mA and was decreased to minimal amperage that elicited the desired motor response. Electrode position was fixed, and electrode current was discontinued. A shielded 22-gauge block needle was advanced through the electrode guide to near the underlying nerve. Initial needle current was only 0.5 mA. Local anesthetic was injected to block the targeted nerve or nerves. Standard sensory/motor testing was performed at 20 minutes. Nine upper or lower extremity blocks were performed on 7 patients. All were successful. Minimal stimulating currents were 1.3 to 8.2 mA for transcutaneous electrode stimulation and 0.20 to 0.70 for needle stimulation. Needle depth was 0.4 to 1.1 cm beyond the electrode tip and correlated with minimal electrode stimulating current. A smooth, metal-tipped electrically shielded skin electrode probe can be used to comfortably and accurately indent the skin over a desired nerve or plexus, define its anatomical course, and subsequently guide a block needle near it.


Syntheses of taiwaniaquinone F and taiwaniaquinol A via an unusual remote C-H functionalization.
A protecting-group-free route to (-)-taiwaniaquinone F based on a ring contraction and subsequent aromatic oxidation of a sugiol derivative is reported. In addition, the first synthesis of (+)-taiwaniaquinol A is reported via short time exposure of (-)-taiwaniaquinone F to sunlight triggering a remote C-H functionalization. The hypothesis that the biogenesis of some methylenedioxy bridged natural products could proceed via similar nonenzymatic mechanisms is presented.


Unified protocol for transdiagnostic treatment of emotional disorders: a randomized controlled trial.
This study further evaluates the efficacy of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP). A diagnostically heterogeneous clinical sample of 37 patients with a principal anxiety disorder diagnosis was enrolled in a randomized controlled trial (RCT) involving up to 18 sessions of treatment and a 6-month follow-up period. Patients were randomly assigned to receive either immediate treatment with the UP (n=26) or delayed treatment, following a 16-week wait-list control period (WLC; n=11). The UP resulted in significant improvement on measures of clinical severity, general symptoms of depression and anxiety, levels of negative and positive affect, and a measure of symptom interference in daily functioning across diagnoses. In comparison, participants in the WLC condition exhibited little to no change following the 16-week wait-list period. The effects of UP treatment were maintained over the 6-month follow-up period. Results from this RCT provide additional evidence for the efficacy of the UP in the treatment of anxiety and comorbid depressive disorders, and provide additional support for a transdiagnostic approach to the treatment of emotional disorders.


Nano-Calorimetry based point of care biosensor for metabolic disease management.
Point of care (POC) diagnostics represents one of the fastest growing health care technology segments. Developments in microfabrication have led to the development of highly-sensitive nanocalorimeters ideal for directly measuring heat generated in POC biosensors. Here we present a novel nano-calorimeter-based biosensor design with differential sensing to eliminate common mode noise and capillary microfluidic channels for sample delivery to the thermoelectric sensor. The calorimeter has a resolution of 1.4 ± 0.2 nJ/(Hz)1/2 utilizing a 27 junction bismuth/titanium thermopile, with a total Seebeck coefficient of 2160 μV/K. Sample is wicked to the calorimeter through a capillary channel making it suitable for monitoring blood obtained through a finger prick (<1 μL sample required). We demonstrate device performance in a model assay using catalase, achieving a threshold for hydrogen peroxide quantification of 50 μM. The potential for our device as a POC blood test for metabolic diseases is shown through the quantification of phenylalanine (Phe) in serum, an unmet necessary service in the management of Phenylketonuria (PKU). Pegylated phenylalanine ammonia-lyase (PEG-PAL) was utilized to react with Phe, but reliable detection was limited to <5 mM due to low enzymatic activity. The POC biosensor concept can be multiplexed and adapted to a large number of metabolic diseases utilizing different immobilized enzymes.


The effects of a partially purified fraction of an ant venom in rheumatoid arthritis.
A partially purified extract of an ant venom from the South American tree ant Pseudomyrmex sp. was tested in a double-blind, controlled study of patients with rheumatoid arthritis. Venom treated patients demonstrated an improvement in global efficacy and a decrease in the number of tender/painful joints and swollen joints. Swollen joint index improved in 60% of venom treated patients. Other parameters did not demonstrate significant change. Reduction of joint swelling was followed by symptomatic improvement that was sometimes delayed by weeks. Reactions were limited to erythema at the injection site (all patients), local pruritus (two-thirds of the patients), and fever with malaise (one-third of the patients). Further study of this venom in rheumatoid arthritis appears warranted in view of its apparent favorable efficacy-to-toxicity ratio.


Nrarp functions to modulate neural-crest-cell differentiation by regulating LEF1 protein stability.
Nrarp (Notch-regulated ankyrin repeat protein) is a small protein that has two ankyrin repeats. Although Nrarp is known to be an inhibitory component of the Notch signalling pathway that operates in different developmental processes, the in vivo roles of Nrarp have not been fully characterized. Here, we show that Nrarp is a positive regulator in the Wnt signalling pathway. In zebrafish, knockdown of Nrarp-a expression by an antisense morpholino oligonucleotide (MO) results in altered Wnt-signalling-dependent neural-crest-cell development. Nrarp stabilizes LEF1 protein, a pivotal transcription factor in the Wnt signalling cascade, by blocking LEF1 ubiquitination. In accordance with this, the knockdown phenotype of lef1 is similar to that of nrarp-a, at least in part, in its effect on the development of multiple tissues in zebrafish. Furthermore, activation of LEF1 does not affect Notch activity or vice versa. These findings reveal that Nrarp independently regulates canonical Wnt and Notch signalling by modulating LEF1 and Notch protein turnover, respectively.


Evolving principles of office quality assurance.
The application of medical quality assurance principles to ambulatory patient care using the traditional methods of medical chart audit, process review, and physician education has yielded generally disappointing results in improving patient care and physician performance. Newer methods assist physicians by providing patient and medical reference data at the time of a patient's visit. Techniques for tracking treatment outcomes and patients' test results and for providing instructions to patients may improve both care and patients' and physicians' satisfaction. This feature appears regularly in THE WESTERN JOURNAL OF MEDICINE. It is intended to cover recent developments in a broad range of issues that will have an impact-either directly or indirectly-on clinical practice. Occasionally the seminars may include informed speculation about likely future developments.


Ischemic peripheral arterial disease and recurrent iliofemoral venous thrombosis in a 24-year-old man with antiphospholipid syndrome.
The following is a case report of a young man with antiphospholipid syndrome, present with a recurrent iliofemoral venous thrombosis and premature peripheral arterial disease. This case report highlights the high risk of recurrent thrombosis upon discontinuation of anticoagulation therapy, particularly in the presence of persistent spontaneously increased aPTT and a high antiphospholipid antibody titer. The case report also reviews the potential of endovascular treatment of iliac vein thrombosis and points out the good 24-month patency rates of stents implanted into the pelvic vein region.Key words: antiphospholipid syndrome - iliofemoral deep vein thrombosis - recurrent thrombosis - accelerated atherosclerosis - peripheral arterial disease.


Detection of circulating and endothelial cell polymers of Z and wild type alpha 1-antitrypsin by a monoclonal antibody.
Globular inclusions of abnormal alpha1-antitrypsin (AAT) in the endoplasmic reticulum of hepatocytes are a characteristic feature of AAT deficiency of the PiZZ phenotype. Monoclonal antibodies, which contain constant specificity and affinity, are often used for the identification of Z-mutation carriers. A mouse monoclonal antibody (ATZ11) raised against PiZZ hepatocytic AAT was successfully used in enzyme-linked immunosorbent assays (ELISA) and in identification of Z-related AAT globular inclusions by immunohistochemical techniques. Using electrophoresis, Western blotting, and ELISA procedures, we have shown in the present study that this monoclonal antibody specifically detects a conformation-dependent neoepitope on both polymerized and elastase-complexed molecular forms of AAT. The antibody has no apparent affinity for native, latent, or cleaved forms of AAT. The antibody ATZ11 illustrates the structural resemblance between the polymerized form of AAT and its complex with elastase and provides evidence that Z-homozygotes beyond the native form may have at least one more circulating molecular form of AAT, i.e. its polymerized form. In addition, staining of endothelial cells with ATZ11 antibody in both M- and Z-AAT individuals shows that AAT attached to endothelial cells is in a polymerized form. The antibody can be a powerful tool for the study of the molecular profile of AAT, not only in Z-deficiency cases but also in other (patho)physiological conditions.


[Genome-wide linkage scan for an ethnic Han Chinese pedigree affected with schizophrenia].
To perform genome-wide linkage analysis for an ethnic Han Chinese pedigree with schizophrenia in order to locate the susceptibility genes. Genomic DNA was extracted from 4 mL of peripheral blood using conventional phenol-chloroform method. Illumina Infinium Linkage 24 BeadChips chip was used for determining the genotypes through detection of single nucleotide polymorphisms (SNPs). After processing the raw data using Illumina BeadStudio software, two-point nonparametric linkage analysis and two-point parametric linkage analysis were performed with Merlin software. By two-point nonparametric linkage analysis, 27 sites with high LOD scores (LOD=0.63-0.75, P U+003C 0.05) were identified. Among these, 3 SNPs(rs993694, rs992690 rs1861577) were located in 12p12.3 region, whilst the remainders were located in 4p12-q22 region. Two-point parametric linkage analysis under a dominant model has yielded almost identical results. Chromosomal regions 4p12-q22 and 12p12.3 probably contain susceptibility genes for schizophrenia.


A process for solvent/detergent treatment of plasma for transfusion at blood centers that use a disposable-bag system.
Solvent/detergent (S/D) inactivates enveloped viruses in plasma. The current technology requires a plasma fractionation facility and is applied to large plasma pools, which increases the cost and risks of exposure to S/D-resistant pathogens and lowers the content of protein S and alpha2-antiplasmin. Two S/D treatment procedures for single donations or minipools of plasma have been developed with a single-use bag system. Frozen plasma samples were thawed and treated in disposable bags with either 2 percent tri(n-butyl)phosphate (TnBP) at 37 degrees C or 1 percent TnBP and 1 percent Triton X-45 at 31 degrees C for 4 hours. Plasma samples were extracted three times with 7.5 percent sterile castor oil to remove TnBP and Triton X-45. The TnBP-treated plasma samples were further subjected to a clarifying centrifugation (3800 x g, 30 min). Final plasma samples were dispensed into individual bags and frozen at -30 degrees C. Plasma quality was assessed at each step of the procedures. Both processes yielded greater than 90 percent mean recovery of coagulation factors (clottable fibrinogen, von Willebrand factor, and factors VIII, V, VII, IX, X, and XI), anticoagulants (protein C, protein S), protease inhibitors (antithrombin, alpha2-antiplasmin), total protein, albumin, and immunoglobulins. Global coagulation tests of the treated plasma samples were normal. Final TnBP and Triton X-45 content was less than 10 and 50 ppm, respectively. S/D treatment of plasma can be performed in a closed-bag system under conditions that maintain plasma protein quality. The technology is simple, presents advantages over the industrial large-scale S/D plasma process, and could be performed in blood centers.


Breakpoints for predicting Pseudomonas aeruginosa susceptibility to inhaled tobramycin in cystic fibrosis patients: use of high-range Etest strips.
Inhaled administration of tobramycin assures high concentrations in cystic fibrotic lungs, improving the therapeutic ratio over that of parenteral tobramycin levels, particularly against Pseudomonas aeruginosa. Conventional Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards) breakpoints only consider parenteral levels and do not take into account these high antimicrobial concentrations. The Spanish Antibiogram Committee (The MENSURA Group) has tentatively defined specific breakpoint values for inhaled tobramycin when testing P. aeruginosa isolates from cystic fibrosis (CF) patients (susceptible, < or =64 microg/ml; resistant, > or =128 microg/ml). The antimicrobial susceptibilities of 206 prospectively collected CF P. aeruginosa isolates were determined by the reference agar dilution method. For tobramycin, the performance of high range tobramycin Etest strips (AB Biodisk, Solna, Sweden) and conventional tobramycin disks were assessed with the same collection. Applying MENSURA proposed breakpoints, 95.1% of the strains were categorized as susceptible to tobramycin, either using agar dilution or Etest high-range strips (99% categorical agreement between both methods). With CLSI breakpoints, susceptibility rates decreased to 79.1 and 81.1% for agar dilution and Etest strips, respectively (83.5% categorical agreement). Minor, major, and very major errors for Etest strips (CLSI criteria) were 13.6, 1.2, and 14.8%, respectively. Upon applying the new proposed criteria for inhaled tobramycin, only one major and one very major error were observed with Etest strips. Whenever inhaled tobramycin is considered for therapy, we suggest that P. aeruginosa strains from CF patients categorized as intermediate or resistant to tobramycin according to the CLSI criteria should be retested with high-range Etest strips and recategorized using MENSURA interpretive criteria. CLSI breakpoints should still be followed when intravenous tobramycin is used in CF patients, particularly during the course of exacerbations.


PKA and CaMKII mediate PI3K activation in bovine sperm by inhibition of the PKC/PP1 cascade.
To enable fertilization, spermatozoa must undergo several biochemical processes in the female reproductive tract, collectively called capacitation. These processes involve protein kinase A (PKA)-dependent protein tyrosine phosphorylation including phosphatidylinositol-3-kinase (PI3K). It is not known how PKA, a serine/threonine (S/T) kinase, mediates tyrosine phosphorylation of proteins. We recently showed that inhibition of S/T phosphatase 1 (PP1) causes a significant increase in phospho-PI3K. In this study, we propose a mechanism by which PKA and PP1 mediate an increase in PI3K tyrosine phosphorylation and implicate calmodulin-dependent kinase II (CaMKII) in this process. Inhibition of sperm PP1 or PKC, stimulated CaMKII phosphorylation/activation, and inhibition of PKC enhanced PP1 phosphorylation/inactivation. Inhibition of CaMKII, using KN-93, caused significant reduction in phospho-PP1, indicating its activation. Moreover, KN-93 prevented the dephosphorylation/inactivation of PKC. We therefore suggest that CaMKII inhibits PKC, leading to PP1 inhibition and the reciprocal auto-activation of CaMKII. Thus, CaMKII can regulate its own activation by inhibiting the PKC/PP1 cascade. Inhibition of Src family kinases (SFK) caused significant inhibition of CaMKII and PP1 phosphorylation, suggesting that SFK activity results in PP1 inhibition and CaMKII activation. Activation of sperm PKA by 8Br-cAMP revealed an increase in phospho-CaMKII, which was inhibited by PKA inhibitor. Tyrosine phosphorylation of PI3K was stimulated by 8Br-cAMP and by PKC or PP1 inhibition and was abrogated by CaMKII inhibition. Furthermore, phosphorylation/activation of the tyrosine kinase Pyk2 was enhanced by PP1 inhibition, and this activation is blocked by CaMKII inhibition. Thus, PKA activates Src, which inhibits PP1, leading to CaMKII and Pyk2 activation, resulting in PI3K tyrosine phosphorylation/activation.


A geometry-driven optical flow warping for spatial normalization of cortical surfaces.
Spatial normalization is frequently used to map data to a standard coordinate system by removing intersubject morphological differences, thereby allowing for group analysis to be carried out. The work presented in this paper is motivated by the need for an automated cortical surface normalization technique that will automatically identify homologous cortical landmarks and map them to the same coordinates on a standard manifold. The geometry of a cortical surface is analyzed using two shape measures that distinguish the sulcal and gyral regions in a multiscale framework. A multichannel optical flow warping procedure aligns these shape measures between a reference brain and a subject brain, creating the desired normalization. The partial differential equation that carries out the warping is implemented in a Euclidean framework in order to facilitate a multiresolution strategy, thereby permitting large deformations between the two surfaces. The technique is demonstrated by aligning 33 normal cortical surfaces and showing both improved structural alignment in manually labeled sulci and improved functional alignment in positron emission tomography data mapped to the surfaces. A quantitative comparison between our proposed surface-based spatial normalization method and a leading volumetric spatial normalization method is included to show that the surface-based spatial normalization performs better in matching homologous cortical anatomies.


A four-dimensional CT-based evaluation of techniques for gastric irradiation.
To evaluate three-dimensional conformal (3D-CRT), intensity-modulated (IMRT) and respiration-gated radiotherapy (RGRT) techniques for gastric irradiation for target coverage and minimization of renal doses. All techniques were four-dimensional (4D)-CT based, incorporating the intrafractional mobility of the target volume and organs at risk (OAR). The stomach, duodenal C-loop, and OAR (kidneys, liver, and heart) were contoured in all 10 phases of planning 4D-CT scans for five patients who underwent abdominal radiotherapy. Planning target volumes (PTVs) encompassing all positions of the stomach (PTV(all phases)) were generated. Three respiratory phases for RGRT in inspiration and expiration were identified, and corresponding PTV(inspiration) and PTV(expiration) and OAR volumes were created. Landmark-based fields recommended for the Radiation Therapy Oncology Group (RTOG) 99-04 study protocol were simulated to assess PTV coverage. IMRT and 3D-CRT planning with and without additional RGRT planning were performed for all PTVs, and corresponding dose volume histograms were analyzed. Use of landmark-based fields did not result in full geometric coverage of the PTV(all phases) in any patient. IMRT significantly reduced mean renal doses compared with 3D-CRT (15.0 Gy +/- 0.9 Gy vs. 20.1 Gy +/- 9.3 Gy and 16.6 Gy +/- 1.5 Gy vs. 32.6 Gy +/- 7.1 Gy for the left and right kidneys, respectively; p = 0.04). No significant increase in renal sparing was seen when adding RGRT to either 3D-CRT or IMRT. Tolerance doses to the other OAR were not exceeded. Individualized field margins are essential for gastric irradiation. IMRT plans significantly reduce renal doses, but the benefits of RGRT in gastric irradiation appear to be limited.


Concatenated hERG1 tetramers reveal stoichiometry of altered channel gating by RPR-260243.
Activation of human ether-a-go-go-related gene 1 (hERG1) K(+) channels mediates repolarization of action potentials in cardiomyocytes. RPR-260243 [(3R,4R)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluorophenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid] (RPR) slows deactivation and attenuates inactivation of hERG1 channels. A detailed understanding of the molecular mechanism of hERG1 agonists such as RPR may facilitate the design of more selective and potent compounds for prevention of arrhythmia associated with abnormally prolonged ventricular repolarization. RPR binds to a hydrophobic pocket located between two adjacent hERG1 subunits, and, hence, a homotetrameric channel has four identical RPR binding sites. To investigate the stoichiometry of altered channel gating induced by RPR, we constructed and characterized tetrameric hERG1 concatemers containing a variable number of wild-type subunits and subunits containing a point mutation (L553A) that rendered the channel insensitive to RPR, ostensibly by preventing ligand binding. The slowing of deactivation by RPR was proportional to the number of wild-type subunits incorporated into a concatenated tetrameric channel, and four wild-type subunits were required to achieve maximal slowing of deactivation. In contrast, a single wild-type subunit within a concatenated tetramer was sufficient to achieve half of the maximal RPR-induced shift in the voltage dependence of hERG1 inactivation, and maximal effect was achieved in channels containing three or four wild-type subunits. Together our findings suggest that the allosteric modulation of channel gating involves distinct mechanisms of coupling between drug binding and altered deactivation and inactivation.


The ticking time-bomb. Health literacy in the context of genetic risk prediction in familial breast-ovarian cancer; A qualitative study.
Personalised methods of predicting breast and ovarian cancer risk through genetic testing increasingly demand a person's understanding and critical appraisal of risk-related information, as well as decision-making and acting upon disclosure of a positive test result. The current study aims at understanding health literacy (HL) among persons at risk of developing familial breast-ovarian cancer (FBOC) from a bottom-up perspective-incorporating their viewpoints into the research process. Its qualitative design integrates an ethnographic-narrative approach and findings from 10 narrative interviews with women who have undergone genetic testing, analysed by using reflexive grounded theory. The collected data reveal the entanglement of the women's perceptions concerning the risk of getting ill, their identity, and their strategies of managing health. The analysis of this interplay provides an empirical basis for approaching HL in its communicative dimension, considering individuals' understandings of health and illness, and emphasizing the role of critical HL.


Aryl-phosphonate lanthanide complexes and their fluorinated derivatives: investigation of their unusual relaxometric behavior and potential application as dual frequency 1H/19F MRI probes.
A series of low molecular weight lanthanide complexes were developed that have high (1)H longitudinal relaxivities (r1) and the potential to be used as dual frequency (1)H and (19)F MR probes. Their behavior was investigated in more detail through relaxometry, pH-potentiometry, luminescence, and multinuclear NMR spectroscopy. Fitting of the (1)H NMRD and (17)O NMR profiles demonstrated a very short water residence lifetime (<10 ns) and an appreciable second sphere effect. At lower field strengths (20 MHz), two of the complexes displayed a peak in r1 (21.7 and 16.3 mM(-1) s(-1)) caused by an agglomeration, that can be disrupted through the addition of phosphate anions. NMR spectroscopy revealed that at least two species are present in solution interconverting through an intramolecular binding process. Two complexes provided a suitable signal in (19)F NMR spectroscopy and through the selection of optimized imaging parameters, phantom images were obtained in a MRI scanner at concentrations as low as 1 mM. The developed probes could be visualized through both (1)H and (19)F MRI, showing their capability to function as dual frequency MRI contrast agents.


Geometric microenvironment directs cell morphology on topographically patterned hydrogel substrates.
Cell behavior is influenced by numerous factors in the physical environment, and a deep understanding of these interactions can lead to the design of better scaffolds for tissue engineering. In vitro substrates can be used to evaluate a wide range of factors, such as topography, and identify which show promise for further evaluating in vivo. Polyacrylamide hydrogels featuring a combinatorial, micropatterned array of posts with varied shape, width, and spacing were produced using a one-step technique. Substrates were covalently modified with collagen and seeded with D1 ORL UVA mesenchymal stem cells. Patterning was shown to direct several quantitative measures of cell morphology. Cell bodies tended to be located in gaps 15mum and wider, but on top of posts when gaps were 5mum and smaller. Cells on substrates with square posts and narrow gaps tended to elongate in the direction of gaps. Finally, smaller gaps on all substrates were also shown to influence the placement of cell extensions. The parameters identified may be incorporated into substrates to direct specific aspects of cell morphology.


Development, linguistic and clinimetric validation of the WOMAC VA3.01 Bangla for Bangladesh Index.
The aim of this study was to develop and to validate a Bengali version of the Western Ontario and McMaster Osteoarthritis (WOMAC) index in Bangladesh. The WOMAC was translated into the local language of Bangladesh (Bengali) and adapted in the local sociocultural context, following the standard guidelines by Beaton et al. Content validity of the preliminary Bengali version was assessed by using the index of content validity (ICV) and floor and ceiling effects. Patients were assessed at the Department of Rheumatology of Bangabandhu Sheikh Mujib Medical University and were diagnosed to have knee OA by American College of Rheumatology criteria and recruited according to the requirements of the validation study. Convergent and divergent validity were measured by comparing with Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36), and internal consistency was assessed using Cronbach's alpha coefficient. The questionnaire was readministered to 40 patients within a week for assessing reliability by using intra-class correlation coefficient (ICC) and Spearman's rank correlation coefficient. In addition, factor analysis of Bengali WOMAC questionnaire was performed to examine the number of factors influencing a common set of items. A Bengali version was developed with changes in three items to suit local practices. The ICV of the content validity was 1 for all items. The Bengali WOMAC had similar construct validity when compared to the HAQ (ρ 0.74, n = 70) and SF-36 bodily pain and physical functioning. It had dissimilar construct validity to SF-36 mental health domain except WOMAC pain. Factor analysis revealed five factors with eigenvalues of more than 1.0. Cronbach's alpha and ICC exceeded 0.7 in all domains. In the test-retest reliability testing, Spearman's ρ for all items exceeded 0.4 (n = 40). This study has demonstrated that the Bengali version of WOMAC is a valid tool for assessing quality of life of patients with knee osteoarthritis in Bangladesh and is reliable.


High Prevalence of Campylobacter ureolyticus in Stool Specimens of Children with Diarrhea in Japan.
Campylobacter ureolyticus has been considered as a potentially pathogenic bacterium. In this study, a total of 586 stool samples were collected from 0-12-year-old children with diarrhea between November 2013 and April 2015 and examined with microbiological tests in the hospital for the diagnosis of common enteric pathogens including C. jejuni and C. coli. Then in our laboratory, these samples were analyzed by 16S rRNA sequence-based Campylobacter genus-specific PCR (C16S PCR); 283 (48.3%) samples showed positive results with this PCR assay. Furthermore, C. ureolyticus was screened in these 283 samples by PCR assay, which can detect this species specifically. Surprisingly, C. ureolyticus was detected in 147 of the 283 C16S PCR-positive diarrheal stool samples (51.9%), which is much higher than the prevalence of C. jejuni and C. coli (15.5%), and 96 samples out of 147 were negative for any of the other enteric pathogens tested in the hospital; namely, C. ureolyticus was detected as a single pathogen in 96 samples. This finding suggests that C. ureolyticus may be a pathogen associated with diarrhea in children in Japan. To the best of our knowledge, this is the first report in which C. ureolyticus was detected among Japanese children with diarrhea.


Attention deficit hyperactivity disorder associated with orbitofrontal epilepsy in a father and a son.
The authors report on a father and son with frontal lobe epilepsy and symptoms of attention deficit hyperactivity disorder (ADHD). Attention deficit hyperactivity is a syndrome defined by criteria that include inattention, impulsive behavior, impaired concentration and motor restlessness. It does not require medical or neurobehavioral evaluation to determine an underlying etiology. The father is a 45-year-old man evaluated for possible ADHD. His referral came after the diagnosis of ADHD in his 6-year-old son who responded well to treatment with methylphenidate HCL. Neurobehavioral evaluation of the father suggested frontal lobe dysfunction. Magnetic resonance imaging and electroencephalography (EEG) were normal. Brain 99mTc HMPAO single-photon emission computed tomography (SPECT) revealed left orbitofrontal hypoperfusion. Additional history from his wife revealed episodic symptoms suggestive of nonconvulsive epilepsy that included nonresponsive staring, complex automatic behavior, and amnesic lacunas. Treatment of the father with carbmazepine produced dramatic improvement. Subsequent evaluation of his son, currently on maintenance treatment with methylphenidate HCL for ADHD, elicited a history consistent with atonic and simple motor partial epilepsy. The son's brain SPECT revealed bilateral orbitofrontal hypoperfusion defects. Attention deficit hyperactivity disorder is a syndrome that may be caused by frontal lobe lesions or epilepsy. In the setting of possible ADHD, neurological evaluation is warranted. Although overreliance on structural imaging or EEG in such an evaluation must be discouraged, brain SPECT may be useful to evaluate patients with symptoms of attention disorders for frontal epilepsy.


Surface properties of Lactobacilli isolated from healthy subject.
Lactobacilli were isolated from mouth, stomach and intestine of healthy subjects and identified by using standard bacteriological methods. The aim of the study was to determine the cell surface characteristics of Lactobacilli and to correlate them with ability to adhere to KB cell line. Our results revealed that all isolated Lactobacillus strains showed basic surface character and those with high hydrophobicity scores and auto-aggregation were highly adherent to KB cell line.


Quantitative three-dimensional intravascular ultrasound.
Three-dimensional (3-D) intravascular ultrasound (IVUS) allows for the visualization of entire coronary segments, provides more detailed insights into the geometry of atherosclerotic plaques and facilitates serial studies. Automated quantitative 3-D IVUS methods reduce the analysis time and the subjectivity of boundary tracing, and permit complex IVUS studies. The 3-D IVUS approach is not restricted to research applications, but may be used as a valuable clinical tool. Evaluation of the coronary segment of interest before catheter-based coronary interventions provides information which may facilitate the selection of interventional devices. Moreover, 3-D IVUS allows for a careful assessment of the procedural results and potential post-procedural complications. ECG-gated image acquisition, automated contour detection, and approaches using data of both 3-D IVUS and biplane angiography represent the recent progress in this field. Three-dimensional IVUS will surely gain further importance and become a routine technique, if the interest and research effort is sustained.


Review of Ehlers-Danlos syndrome. Successful repair of rupture and dissection of abdominal aorta.
Successful surgical treatment of spontaneous rupture and dissection of the abdominal aorta in Ehlers-Danlos syndrome has not been previously reported. A 16-year-old male sustained spontaneous rupture and dissection of the abdominal aorta. Successful surgical treatment included placement of an abdominal aortic bifurcation graft. Genetical, biochemical and clinical differences of seven types of the syndrome are outlined. A brief guideline for treatment and prevention of vascular complications is discussed.


Local infiltration analgesia in hip and knee arthroplasty: an emerging technique.
The optimal form of post-operative analgesia in hip and knee arthroplasty is still debated. Traditionally, patient-controlled analgesia and epidural anaesthesia were used. Potential side-effects such as nausea, confusion, urinary retention, hypotension and immobility have resulted in the emergence of newer techniques that limit opioid use. Peripheral nerve blockade provides excellent analgesia but limits patient ability to ambulate in the immediate post-operative period. Local infiltrative analgesia (LIA) is an emerging technique that has shown to provide superior analgesia, higher patient satisfaction and earlier discharge from hospital when compared to some of the more traditional methods. This review article highlights the advantages of LIA in hip and knee arthroplasty surgery. We describe the technique used, including additional measures that aid early ambulation and discharge from hospital in this cohort of patients.


Assessment of Vegetation Indices Derived by UAV Imagery for Durum Wheat Phenotyping under a Water Limited and Heat Stressed Mediterranean Environment.
There is growing interest for using Spectral Vegetation Indices (SVI) derived by Unmanned Aerial Vehicle (UAV) imagery as a fast and cost-efficient tool for plant phenotyping. The development of such tools is of paramount importance to continue progress through plant breeding, especially in the Mediterranean basin, where climate change is expected to further increase yield uncertainty. In the present study, Normalized Difference Vegetation Index (NDVI), Simple Ratio (SR) and Green Normalized Difference Vegetation Index (GNDVI) derived from UAV imagery were calculated for two consecutive years in a set of twenty durum wheat varieties grown under a water limited and heat stressed environment. Statistically significant differences between genotypes were observed for SVIs. GNDVI explained more variability than NDVI and SR, when recorded at booting. GNDVI was significantly correlated with grain yield when recorded at booting and anthesis during the 1st and 2nd year, respectively, while NDVI was correlated to grain yield when recorded at booting, but only for the 1st year. These results suggest that GNDVI has a better discriminating efficiency and can be a better predictor of yield when recorded at early reproductive stages. The predictive ability of SVIs was affected by plant phenology. Correlations of grain yield with SVIs were stronger as the correlations of SVIs with heading were weaker or not significant. NDVIs recorded at the experimental site were significantly correlated with grain yield of the same set of genotypes grown in other environments. Both positive and negative correlations were observed indicating that the environmental conditions during grain filling can affect the sign of the correlations. These findings highlight the potential use of SVIs derived by UAV imagery for durum wheat phenotyping under low yielding Mediterranean conditions.


Simple method to determine beta-lactam resistance phenotypes in Pseudomonas aeruginosa using the disc agar diffusion test.
Pseudomonas aeruginosa is a major opportunistic bacterial pathogen in nosocomial infections because of the increasing prevalence of resistance to many of the commonly used antibiotics. To ensure optimal efficiency of antibiotic treatment against this species, antibiotic susceptibility tests must be interpreted with caution. Most microbiologists now consider it essential to characterize the antibiotic resistance expressed by isolates. Particular resistance mechanisms may be suspected when the bacterium is resistant to several antibiotics in the same family (for example beta-lactam agents). Using the disc agar diffusion test, a simple method was developed to distinguish between the common beta-lactam resistance phenotypes of P. aeruginosa and, consequently, the possible resistance mechanism(s). Over a period of 5 years, we analysed 6300 P. aeruginosa strains isolated from various pathological specimens collected from different wards of Cochin Port-Royal Hospital, and reference and collection strains. Each strain had the wild-type phenotype or an acquired resistance phenotype. Eight anti-pseudomonal beta-lactams (ticarcillin, cefotaxime or moxalactam, cefepime or cefpirome, imipenem, ceftazidime, aztreonam, cefsulodin and ticarcillin + clavulanic acid) were used as phenotypic markers. The following markers were sufficient to distinguish between the wild-type phenotype and the various acquired resistance phenotypes: beta-lactamase synthesis, reduced cell wall permeability and/or increased expression of efflux transporters (active efflux). Detection of resistance phenotypes allows 'interpretive reading' of antibiotic susceptibility tests. Clearly, improved interpretation of antibiotic susceptibility tests is important for a better appreciation of the effect of antimicrobial agents on bacteria such as P. aeruginosa.


28S rRNA sequences for Linguatula spp.
Identification of specimens belonging to the genus Linguatula (Pentastomida) is relatively easy due to their unique morphology. However, differentiation between species of Linguatula can be challenging for several reasons, including considerable differences between different developmental stages of the parasite within and between species. Currently, 18S rRNA and Cox1 sequences are the only available comparable sequences in GenBank, but recent research has discussed the utility of 28S rRNA for pentastomid phylogenetics. This study presents 28S rRNA gene sequences for two members of the genus Linguatula. Sequences of 28S rRNA were successfully obtained from well-identified samples of L. serrata (collected in Australia) and L. nuttalli (collected in South Africa), with voucher specimens. Phylogenetic analysis of the 28S rRNA region showed 6% difference between L. serrata and L. nuttalli, with low levels of intraspecific variation. In comparison, 18S rRNA and Cox1 sequences from the same specimens showed 0.23% and 13% interspecific differences, respectively. The results of this study show that 28S rRNA has greater genetic diversity to allow for improved differentiation between species of Linguatula than 18S rRNA but is on par with Cox1. Records that do not provide adequate morphological or molecular data to justify independent specific diagnoses must be regarded cautiously, and the need for continued research on species of Linguatula, using a combined morphological and molecular analysis, across a number of different hosts, development stages, geographical regions and molecular markers is highlighted.


Left atrial appendage thrombus on full-dose dabigatran treatment: a case report.
Dabigatran is a direct competitive thrombin inhibitor approved for stroke prevention in non-valvular atrial fibrillation. At full-dose, dabigatran showed similar rates of bleedings and higher efficacy compared to warfarin. We report a case of acute ischaemic stroke in a patient treated with dabigatran 150 mg b.i.d. for atrial fibrillation. After an off-label treatment with idarucizumab, a humanized monoclonal antibody approved for dabigatran reversal, we performed a successful intravenous thrombolysis (IVT). Transoesophageal echocardiography showed a left atrial appendage (LAA) thrombus, despite full-dose dabigatran and an adequate therapy adherence. There are few cases of LAA thrombus during dabigatran treatment reported in literature till date. We analyse the possible pathogenetic mechanisms involved in dabigatran failure, including drug interactions and unexpected genetic variations interfering with dabigatran serum levels suggesting periodical assessment of direct Oral Anticoagulant levels. Furthermore, we confirm initial reports of safety and efficacy of intravenous thrombolysis after idarucizumab, in case of dabigatran failure.


Immune responses against hepatitis C virus structural proteins following genetic immunisation.
We have used direct DNA inoculation to study the in vivo induction of both humoral and cellular immune responses to hepatitis C virus (HCV) encoded structural antigens. Following immunisation of mice, immune responses were compared using plasmids encoding full-length or partial HCV gene sequences for the nucleocapsid and envelope E2 proteins. Plasmids encoding secreted or non-secreted forms of the immunogens, including constructs expressing HCV sequences fused with the hepatitis B virus surface antigen (HCV-HBV chimeras), were evaluated. Results indicate that: (i) all constructs induced specific anti-HCV antibodies; (ii) antibody titres ranged from 1:100 to > 1:100,000; (iii) all HCV DNA immunogens induced a predominant Th1 response with the induction of IgG2a antibodies; (iv) the secretion level of the antigens and immune responses was not always correlated and (v) CTL could be detected against both HCV and HBV determinants.


Implementation of an attention training programme with a sample of children who have sustained traumatic brain injuries in South Africa: A pilot study.
This pilot study evaluated the feasibility of implementing an attention-training programme for children who have sustained moderate-to-severe traumatic brain injuries (TBIs) in a South African context. We compared the performance on the programme of children with TBI (TBI Intervention Group) to children who had been diagnosed with Attention Deficit Hyperactivity Disorder (ADHD Intervention Group), a TBI Art group and a TBI No-intervention Group (n=5 in each group) in this preliminary study. Children in the two Intervention Groups participated in the "Pay Attention!" programme for 45 minutes twice a week for 12 weeks. All children were aged 6-8 years and underwent neuropsychological testing pre- and post-intervention. Behavioural data were collected from parents. Children in the ADHD Intervention Group showed individual clinically significant attentional improvements on measures of the Conners' Continuous Performance Test II using the Reliable Change Index (≥ 2.58 SD). Despite mixed results, the pilot study demonstrates that implementing a cognitive rehabilitation programme in South Africa is feasible and necessary, despite limited infrastructure and access to resources.


Importance of main-chain flexibility and the insulin fold in insulin-receptor interactions.
We have investigated the effects of altering the disposition between the COOH-terminal B chain domain of insulin and the core of the insulin molecule on ligand interactions with the hepatocyte insulin receptor. Analogues include those in which ArgB22 of des-octapeptide(B23-B30)-insulin is extended by one to three residues of glycine prior to termination in Phe-NH2, by one to five residues of glycine prior to termination in Phe-Phe-NH2, or by an additional residue of glycine prior to termination in more extended sequences derived from insulin or [GlyB24]insulin. Analogues were also examined with respect to their abilities to form hexamers in solution in the presence of Co2+, phenol, and NaSCN. Overall, our studies of ligand-receptor interactions identify that (a) the energetic penalty for the introduction of a single residue of glycine is uniform in all classes of analogues for up to three residues of glycine but diminishes somewhat for analogues with longer insertions and (b) the COOH-terminal residues of the B chain retain their importance for all classes of analogues, no matter the number of glycine residues introduced. Analogues with glycine insertions, but not those with glycine substitutions, readily form thiocyanate-stabilized complexes with Co2+ in the presence of phenol.(ABSTRACT TRUNCATED AT 250 WORDS)


Negative Affect and Excessive Alcohol Intake Incubate during Protracted Withdrawal from Binge-Drinking in Adolescent, But Not Adult, Mice.
Binge-drinking is common in underage alcohol users, yet we know little regarding the biopsychological impact of binge-drinking during early periods of development. Prior work indicated that adolescent male C57BL6/J mice with a 2-week history of binge-drinking (PND28-41) are resilient to the anxiogenic effects of early alcohol withdrawal. Herein, we employed a comparable Drinking-in-the-Dark model to determine how a prior history of binge-drinking during adolescence (EtOHadolescents) influences emotionality (assayed with the light-dark box, marble burying test, and the forced swim test) and the propensity to consume alcohol in later life, compared to animals without prior drinking experience. For additional comparison, adult mice (EtOHadults) with comparable drinking history (PND56-69) were subdivided into groups tested for anxiety/drinking either on PND70 (24 h withdrawal) or PND98 (28 days withdrawal). Tissue from the nucleus accumbens shell (AcbSh) and central nucleus of the amygdala (CeA) was examined by immunoblotting for changes in the expression of glutamate-related proteins. EtOHadults exhibited some signs of hyperanxiety during early withdrawal (PND70), but not during protracted withdrawal (PND98). In contrast, EtOHadolescents exhibited robust signs of anxiety-l and depressive-like behaviors when tested as adults on PND70. While all alcohol-experienced animals subsequently consumed more alcohol than mice drinking for the first time, alcohol intake was greatest in EtOHadolescents. Independent of drinking age, the manifestation of withdrawal-induced hyperanxiety was accompanied by reduced Homer2b expression within the CeA and increased Group1 mGlu receptor expression within the AcbSh. The present data provide novel evidence that binge-drinking during adolescence produces a state characterized by profound negative affect and excessive alcohol consumption that incubates with the passage of time in withdrawal. These data extend our prior studies on the effects of subchronic binge-drinking during adulthood by demonstrating that the increase in alcoholism-related behaviors and glutamate-related proteins observed in early withdrawal dissipate with the passage of time. Our results to date highlight a critical interaction between the age of binge-drinking onset and the duration of alcohol withdrawal in glutamate-related neuroplasticity within the extended amygdala of relevance to the etiology of psychopathology, including pathological drinking, in later life.


Protein S-acyl transferase 4 controls nucleus position during root hair tip growth.
Protein S-acyl transferases (PATs) play critical roles in plant developmental and environmental responses by catalyzing S-acylation of substrate proteins, most of which are involved in cellular signaling. However, only few plant PATs have been functionally characterized. We recently demonstrated that Arabidopsis PAT4 mediates root hair elongation by positively regulating the membrane association of ROP2 and actin microfilament organization. Here, we show that apex-associated re-positioning of nucleus during root hair elongation was impaired by PAT4 loss-of-function. Results presented here pose a significant question concerning the molecular machinery mediating nuclear migration during root hair growth.


Combined transcatheter device closure of ruptured sinus of valsalva and a post-surgical residual ventricular septal defect.
Sinus of Valsalva aneurysms are commonly associated with ventricular septal defects (VSDs). We describe a 14-year-old boy who presented with rupture of right sinus of Valsalva (RSOV) into the right ventricular outflow tract (through two openings) along with a residual VSD, four years after surgical closure of the VSD. Both antegrade and retrograde approaches were used to close the RSOV defects. The larger defect was closed from the venous side using an Amplatzer Duct Occluder (ADO-I) device while the smaller defect was closed from the arterial end using and ADO-II device. The residual VSD was also closed percutaneously using a ADO-I device. Successful transcatheter closure of all defects was possible thereby preventing the morbidity and mortality associated with a repeat surgery.


[Litholytic therapy for urate nephrolithiasis].
To evaluate the effectiveness of ESWL combined with litholytic therapy in patients with uric acid kidney stones. A total of 59 patients with urate nephrolithiasis were observed at the Department of Urology, First Pavlov SMU of St. Peterburg. The patients were divided into two groups according to the treatment regimen. The study group comprised 30 patients who were administered litholytic therapy before ESWL. The comparison group included 29 patients with nephrolithiasis who underwent ESWL without prior litholytic therapy. After 4 weeks of treatment with Blemaren, in 60% of patients of the study group a decrease in the calculus size was noted; in 83.3% of patients according to MSCT there was a decrease in calculus density. Disintegration of kidney stones after a single ESWL session was achieved in 86.7% of patients of the study group and in 65.5% of patients of the control group. The results of this study allow us to recommend a 4-week course of Blemaren to treat patients with urate nephrolithiasis to prepare for ESWL.


Analysis of the presence and physiological relevance of subconducting states of Connexin43-derived gap junction channels in cultured human corporal vascular smooth muscle cells.
Subconductance states are a commonly observed feature of gap junction channels. Their overt frequency and consistent appearance in both single and multichannel records have led to speculation that they might be of physiological importance in terms of altering the rate of small solute transfer from cell to cell. Among the connexin gene family, connexin43 (Cx43) is the most ubiquitous connexin that has been shown to generate subconductive states. Therefore, it was the explicit aim of this investigation to more fully evaluate the potential contribution of human Cx43-derived subconducting states to intercellular communication in cultured human corporal vascular smooth muscle cells. To determine the weight of subconductive states in our records, we analyzed amplitude histograms of multichannel and single-channel data during the application of transjunctional voltages larger than expected for physiological conditions but still smaller than transjunctional voltages known to induce lower conductive states (Vo>Vj). The data clearly indicated that the subconducting states occupy only a small fraction of the total channel open time. This was reflected by the fact that the average open probability for the subconductive state(s) determined from the 9 records analyzed was approximately 2%. Closer inspection of the data revealed that the frequency of subconductive states was actually higher than the frequency of the main state conductance. In summary, recording conditions sufficient for evaluation of the intrinsic gating characteristics of human Cx43-derived gap junction channels have been used. Under these conditions, our data clearly indicate that despite their greater frequency, the duration of subconductance events is so short relative to the main state duration as to render them physiologically insignificant.


Sorption of Sb(III) and Sb(V) to goethite: influence on Sb(III) oxidation and mobilization.
Antimony is an element of growing interest for a variety of industrial applications, even though Sb compounds are classified as priority pollutants by the Environmental Protection Agency of the United States. Iron (Fe) hydroxides appear to be important sorbents for Sb in soils and sediments, but mineral surfaces can also catalyze oxidation processes and may thus mobilize Sb. The aim of this study was to investigate whether goethite immobilizes Sb by sorption or whether Sb(III) adsorbed on goethite is oxidized and then released. The sorption of both Sb(III) and Sb(V) on goethite was studied in 0.01 and 0.1 M KClO4 M solutions as a function of pH and Sb concentration. To monitor oxidation processes Sb species were measured in solution and in the solid phase. The results show that both Sb(III) and Sb(V) form inner-sphere surface complexes at the goethite surface. Antimony(III) strongly adsorbs on goethite over a wide pH range (3-12), whereas maximum Sb(V) adsorption is found below pH 7. At higher ionic strength, the desorption of Sb(V) is shifted to lower pH values, most likely due to the formation of ion pairs KSb(OH)6 degrees. The sorption data of Sb(V) can be fitted by the modified triple-layer surface complexation model. Within 7 days, Sb(III) adsorbed on goethite is partly oxidized at pH 3, 5.9 and 9.7. The weak pH-dependence of the rate coefficients suggests that adsorbed Sb(III) is oxidized by 02 and that the coordination of Sb(III) to the surface increases the electron density of the Sb atom, which enhances the oxidation process. At pH values below pH 7, the oxidation of Sb(III) did not mobilize Sb within 35 days, while 30% of adsorbed Sb(III) was released into the solution at pH 9.9 within the same time. The adsorption of Sb(III) on Fe hydroxides over a wide pH range may be a major pathway for the oxidation and release of Sb(V).


A quantitative comparison of traditional and non-peroxide bleaching agents.
Single-rooted premolar teeth, stained with blood utilizing the technique devised by Freccia & Peters (1981), were subjected to traditional and non-peroxide bleaching agents. Colour changes were recorded over a period of 7 days using a Speedmaster R75-CP Reflection Densitometer. The most efficient removal of staining occurred after the application of 30% hydrogen peroxide, with sodium perborate being 75% as effective. All bleaching agents realized their optimum efficacy within the first 3 days. A combination of three enzymes (amylase, lipase and trypsin) with disodium edetate was not as effective as the routine bleaching agents; however, the combination did have a modifying effect on the blood stains. It is suggested that other non-peroxide agents should be investigated to determine their efficacy in removing staining from experimentally induced blood-stained teeth.


[Medical treatment of Behçet's disease].
The treatment of Behçet's disease is essentially symptomatic and depends on the severity of the manifestations. Colchicine is usefull in the minor, particularly mucocutaneous forms. It can be safely used at a dose of 1 mg/day as maintenance treatment to prevent or limit the acute episodes. Other immunomodulators have been proposed: levamisole, disulon, thalidomide, the indications for which are limited by the side effects. Non-steroidal anti-inflammatory agents are indicated in the articular forms. Steroid therapy remains essential in the severe neurological and ophthalmological forms at an initial dose of 1 mg/kg/day. It can be preceded by the intravenous bolus administration of high doses of methylprednisolone. Immunosuppressants are useful in the same indications. Although some authors propose them right from the start, we prefer to reserve them for second line treatment in the event of steroid dependence or recurrence, because of their short-term infectious and long-term oncogenic risks. Cyclosporin, which has been proven to be effective by randomized studies, is difficult to manage and responsible for complications, in particular renal. It can therefore only be used as second line treatment by experienced users. Plasmapheresis is reserved as an emergency procedure for functionally threatening forms. Venous or arterial thromboses justify long-term anticoagulation, possibly associated with platelet anti-aggregants. In this chronic disease, the quality of follow-up and the patient's cooperation are essential in order to intervene rapidly and to detect as early as possible the complications of the disease and of the treatment.


The effect of item observability, clarity and wording on patient/nurse ratings when using the ASA scale.
Many studies show discrepancies between patients' and professionals' ratings on the same questionnaire regarding the patient's health. A relevant question is whether the differences in ratings reflect real differences between patients and professionals or whether they are caused by characteristics of the instrument. In this study, we address the latter option by examining the effects of 3 item characteristics (item wording, observability and clarity) on the degree of patient/nurse discrepancies in ratings of the items of the Appraisal of Self-care Agency (ASA) scale. Secondary analysis on 252 patient/nurse ratings showed that item wording (positively and negatively formulated items), and the observability of the items have a significant effect on the mean absolute difference score. No effect was found for clarity. These results were generally confirmed by subgroup analyses.


Understanding the implications of the biobehavioral basis of nicotine addiction and its impact on the efficacy of treatment.
Tobacco use remains the leading cause of preventable death in the United States. There are efficacious behavioral and pharmacological options for smoking cessation including three FDA approved therapies - nicotine replacement therapy, varenicline and bupropion. Nevertheless, uptake of smoking cessation treatments continues to be poor and there is a need for novel smoking cessation treatments. Areas covered: This article reviews the biobehavioral basis of nicotine addiction, its implications for smoking cessation treatments, the various neurotransmitter systems involved in nicotine addictive effects, and their potential therapeutic value. Included are discussions around the role of genetic factors in predicting response to pharmacotherapy and what we know about appropriate application of pharmacotherapy and behavioral interventions for tobacco use disorder. The evidence for harm reduction measures in individuals who are not willing or able to quit smoking is also reviewed. Expert commentary: Many neurotransmitter system targets have been investigated as a result of our understanding of the underlying neurobiology of tobacco use disorder, and there remain important targets that have yet to be fully explored. rTMS or combination therapies are proposed as possible novel strategies to improve smoking cessation.


Functional organization of trigeminal subnucleus interpolaris: nociceptive and innocuous afferent inputs, projections to thalamus, cerebellum, and spinal cord, and descending modulation from periaqueductal gray.
In view of continuing uncertainties concerning the organization, afferent inputs, and projection sites of neurons in the subnucleus interpolaris of the trigeminal (V) spinal tract nucleus, the characteristics of 222 single neurons in and adjacent to the subnucleus were examined electrophysiologically in adult cats anesthetized with chloralose. Neurons were tested for orthodromic responsiveness to a variety of stimuli that included nonnoxious tactile stimuli, noxious mechanical and radiant-heat stimuli, and graded electrical stimulation of the skin, mucosa, tooth pulp, and masseter nerve. Antidromic activation techniques were also used to determine if the functionally identified neurons projected directly to the contralateral posterior thalamus, ipsilateral cerebellum, or cervical spinal cord. In addition, the periaqueductal gray matter (PAG) was stimulated to test for conditioning influences from the PAG on orthodromic responses to noxious and nonnoxious oral-facial stimuli. Interpolaris neurons were somatotopically arranged in subnucleus interpolaris in a pattern conforming in general to the medially facing, inverted-head representation characteristic of other parts of the V brain stem sensory nuclear complex. On the basis of their responsiveness to cutaneous stimuli, the neurons could be functionally classified as either cutaneous nociceptive or low-threshold mechanoreceptive (LTM) neurons. The LTM neurons constituted the major neuron type, accounting for over 75% of our neuron sample. Most of them had a localized mechanoreceptive field of less than 100 mm2 in area that was restricted to one V division, and they had skin-evoked response latencies indicative of afferent input predominantly from A-beta cutaneous afferents. A population of nociceptive neurons was also encountered in the lateral, marginal region of interpolaris and at its medial or ventral border with the reticular formation. These neurons were of two types: nociceptive-specific (NS) neurons, which did not respond to nonnoxious stimuli but which required noxious stimuli for their activation; and wide dynamic range ( WDR ) neurons, which responded to both noxious and nonnoxious stimuli applied to the facial skin. Most had an ipsilateral receptive field that was greater than 100 mm2 in area and that often involved two or three V divisions. Their properties generally conformed to those previously described for nociceptive neurons in the medullary dorsal horn (V subnucleus caudalis) and spinal cord dorsal horn. Interpolaris neurons of all classes (LTM, WDR , and NS) were found to have direct axonal projections to the thalamus, cerebellum, and spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)


Smooth stable manifolds for the non-instantaneous impulsive equations with applications to Duffing oscillators.
In this paper, we present a theory of smooth stable manifold for the non-instantaneous impulsive differential equations on the Banach space or Hilbert space. Assume that the non-instantaneous linear impulsive evolution differential equation admits a uniform exponential dichotomy, we give the conditions of the existence of the global and local stable manifolds. Furthermore, C k -smoothness of the stable manifold is obtained, and the periodicity of the stable manifold is given. Finally, an application to nonlinear Duffing oscillators with non-instantaneous impulsive effects is given, to demonstrate the existence of stable manifold.


Autonomic dysreflexia and telehealth.
With the rapid expansion of telehealth lines in the United States and the establishment of provincially funded lines in Canada, a growing number of people use this convenient approach to establish their initial health needs and to pursue self-care. Telehealth providers, for the most part, rely on electronic protocols to offer triaging and advice. Unfortunately, standard protocols are misleading when a premorbid health condition such as a spinal cord injury is present. Symptoms such as a headache, diaphoresis or an elevated blood pressure, which are common occurrences in the general population, may indicate an emergency situation, namely autonomic dysreflexia (AD), when a mid-thoracic and higher spinal cord lesion is present. Since there is no available electronic protocol on AD, this emergency health condition is not recognized by the telehealth provider and may put the caller at risk of serious morbidity or even death. In this article, the authors present the clinical features of AD, the precipitating factors and the nursing management of an episode. The merits and pitfalls of electronic protocols are reviewed and an algorithm is presented to assist telehealth providers in recognizing AD.


Optical spectroscopy of rare earth ion-doped TiO2 nanophosphors.
Trivalent rare-earth (RE3+) ion-doped TiO2 nanophosphors belong to one kind of novel optical materials and have attracted increasing attention. The luminescence properties of different RE3+ ions in various TiO2 nanomaterials have been reviewed. Much attention is paid to our recent progresses on the luminescence properties of RE3+ (RE = Eu, Er, Sm, Nd) ions in anatase TiO2 nanoparticles prepared by a sol-gel-solvothermal method. Using Eu3+ as a sensitive optical probe, three significantly different luminescence centers of Eu3+ in TiO2 nanoparticles were detected by means of site-selective spectroscopy at 10 K. Based on the crystal-field (CF) splitting of Eu3+ at each site, C2v and D2 symmetries were proposed for Eu3+ incorporated at two lattice sites. A structural model for the formation of multiple sites was proposed based on the optical behaviors of Eu3+ at different sites. Similar multi-site luminescence was observed in Sm(3+)- or Nd(3+)-doped TiO2 nanoparticles. In Eu(3+)-doped TiO2 nanoparticles, only weak energy transfer from the TiO2 host to the Eu3+ ions was observed at 10 K due to the mismatch of energy between the TiO2 band-gap and the Eu3+ excited states. On the contrary, efficient host-sensitized luminescences were realized in Sm(3+)- or Nd(3+)-doped anatase TiO2 nanoparticles due to the match of energy between TiO2 band-gap and the Sm3+ and Nd3+ excited states. The excitation spectra of both Sm(3+)- and Nd(3+)-doped samples exhibit a dominant broad peak centered at approximately 340 nm, which is associated with the band-gap of TiO2, indicating that sensitized emission is much more efficient than direct excitation of the Sm3+ and Nd3+ ions. Single lattice site emission of Er3+ in TiO2 nanocrystals can be achieved by modifying the experimental conditions. Upon excitation by a Ti: sapphire laser at 978 nm, intense green upconverted luminescence was observed. The characteristic emission of Er3+ ions was obtained both in the ultraviolet-visible (UV-vis) and near-infrared regions through the high-resolution experiments at 10 K. The CF experienced by Er3+ in TiO2 nanocrystal was systematically studied by means of the energy level fitting.


Takotsubo cardiomyopathy after intravenous epinephrine administration following cardiac arrest provoked by pneumoperitoneum - a case report.
In stress-induced takotsubo cardiomyopathy (TC) high levels of catecholamines, including epinephrine, may be detected in blood. On the other hand, administration of exogenous epinephrine may occasionally result in TC. The authors describe a case of a 58-year-old, otherwise healthy female, with TC which occurred after intravenous injection of 1 mg of epinephrine against cardiac arrest provoked by pneumoperitoneum performed before planned laparoscopic cholecystectomy. She was admitted 3 days earlier due to biliary colic following a dietary mistake. Bradycardia followed by asystole took place immediately after carbon dioxide insufflation into the peritoneal cavity. Normal heart rhythm, with transient tachycardia, recurred after a short cardiac massage, intravenous atropine and epinephrine administration as well as pneumoperitoneum decompression. ECG after the episode showed nonspecific ST segment changes. Left ventricular dysfunction assessed in echocardiography as contractile abnormalities and decreased global longitudinal strain (GLS) represented an unusual type of TC - intermediate between mid-basal and focal one. These abnormalities, involving mainly the posterior wall, resolved rapidly within 24 hours without any specific treatment. The absence of coronary artery disease was confirmed by 128-row multidetector computed tomography. TC should be considered as a potential complication of epinephrine action; however, different factors related to laparoscopic procedure including general anesthesia, intubation, underlying disease and mental stress might have been also involved in TC triggering in the case presented.


Does low maternal blood pressure during pregnancy increase the risk of perinatal death?
A recent report described an association between low maximum diastolic blood pressure (DBP) during pregnancy and perinatal death (stillbirth and death in the first week combined). The authors did not account for gestational length, a strong predictor of perinatal death. We studied 41,089 singleton pregnancies from the U.S. Collaborative Perinatal Project (1959-1966). We observed an association between low maximum DBP and elevated risk of perinatal death. However, this association disappeared after accounting for reverse causation related to gestational length. At any given gestational week, women whose offspring ultimately experienced perinatal death did not have significantly lower maximum DBP than women whose offspring survived the perinatal period. When accounting for the trend of increasing DBP during late pregnancy through gestational-age-specific DBP standardized score, we saw no association between low diastolic blood pressure and perinatal death. Low maximum maternal DBP during pregnancy is a post hoc correlate of perinatal death, not a true risk factor.


Idiopathic spinal extradural lipomatosis in a non-obese otherwise healthy man.
Spinal extradural lipomatosis is rare and is usually associated with long-term steroid administration or obesity. It is most commonly thoracic in situation. We present a unique case of spinal extradural lipomatosis in a 20-year-old non-obese, clinically normal man. The role of MRI in investigation and the management options are discussed.


Arterial and venous plasma catecholamines during submaximal steady-state exercise.
Arterial and venous plasma catecholamine responses to 15 min of cycling at 60% of maximal oxygen uptake were examined 11 times during exercise and recovery in nine young men. Intra-arterial blood pressure, heart rate and oxygen uptake were recorded continuously. All variables increased significantly during the initial 4 min, after which oxygen uptake, diastolic blood pressure and arterial plasma adrenaline showed no further increase. Heart rate and plasma noradrenaline, however, continued to increase, although significantly more slowly, and were closely correlated (r = 0.81, 95% CI 0.71-0.87), as were systolic blood pressure and heart rate (r = 0.78, 95% CI 0.71-0.87). Venous plasma adrenaline showed a steady increase during the whole exercise period and thus a different response pattern from arterial plasma adrenaline. In conclusion, arterial plasma catecholamines respond to steady-state exercise by a two-phase pattern paralleling the changes in arterial blood pressure and heart rate. Venous sampling does not reveal this association.


Oocyte Developmental Competence: Insights from Cross-Species Differential Gene Expression and Human Oocyte-Specific Functional Gene Networks.
Understanding oocyte developmental competence remains a key challenge for reproductive biology and systems sciences. The transcriptome of oocytes in eutherians is highly complex and is associated with the success of embryo development. Due to sample limitations from humans, animal models are used for investigation of the oocyte transcriptome. Nonetheless, little is known about the diversity of the oocyte transcriptome across eutherians. In this report, comprehensive investigation of 7 public data sets in 4 species, human, macaque, mice, and cattle, shows that 16,572 genes are expressed in oocytes. Approximately 26% of the genes were expressed in all four species. There were 1390, 489, and 187 genes specifically expressed in human, mice, and cattle oocytes, respectively. Coexpression clustering of the genes specifically expressed in human oocytes revealed functional enrichment (FDR <0.05) of Gene Ontology (GO) terms important for oocyte physiology (i.e., "cellular response to metal ion," "negative regulation of growth," "hormone activity," and "receptor activity"). Interrogation of 4 data sets revealed 26 genes whose expressions were significantly (FDR ≤0.1) associated with oocyte developmental competence and concordant fold change in 2 studies. The genes AK2, AKAP1, ECHS1, MRPL10, MRPL24, PTRH2, STX17, SUCLG1, SUOX, and TOMM34 were associated with the GO term "mitochondrion" (FDR <0.01). Collectively, the results offer new insights on gene transcript levels associated with oocyte developmental competence and the central role of mitochondrion for oocyte's health among eutherians. Caution should be exercised, however, when extending the inferences related to gene expression associated with oocyte quality across eutherians.


Postnatal Ethanol-Induced Neurodegeneration Involves CB1R-Mediated β-Catenin Degradation in Neonatal Mice.
Alcohol consumption by pregnant women may produce neurological abnormalities that affect cognitive processes in children and are together defined as fetal alcohol spectrum disorders (FASDs). However, the molecular underpinnings are still poorly defined. In our earlier studies, we found that ethanol exposure of postnatal day 7 (P7) mice significantly induced widespread neurodegeneration mediated via endocannabinoids (eCBs)/cannabinoid receptor type 1 (CB1R). In the current study, we examined changes in the β-catenin protein levels that are involved in the regulation of neuronal function including neuronal death and survival. We found that moderate- and high-dose postnatal ethanol exposure (PEE) significantly reduced active-β-catenin (ABC) (non-phosphorylated form) protein levels in the hippocampus (HP) and neocortex (NC). In addition, we found that moderate- and high-dose PEE significantly increased the phosphorylated-β-catenin (p-β-catenin)/ABC ratios in the HP and NC. Antagonism/null mutation of CB1R before PEE to inhibit CC3 production mitigated the loss of ABC protein levels. Collectively, these findings demonstrated that the CB1R/β-catenin signaling mechanism causes neurodegeneration in neonatal mouse brains following PEE.


The relationship of Campylobacter jejuni infection and the development of Guillain-Barré syndrome.
Campylobacter jejuni is recognized as the most common infectious agent associated with the development of Guillain-Barré syndrome. Available information on the complete genome sequence of C. jejuni NCTC 11168 has helped researchers to identify polysaccharide capsules as well as genetic mechanisms in the synthesis of ganglioside-like cell surface molecules in this bacteria. Toxins may contribute to the host's inflammatory response seen in Guillain-Barré syndrome.


Dynamic headspace solid-phase microextraction combined with one-dimensional gas chromatography-mass spectrometry as a powerful tool to differentiate banana cultivars based on their volatile metabolite profile.
In this study the effect of the cultivar on the volatile profile of five different banana varieties was evaluated and determined by dynamic headspace solid-phase microextraction (dHS-SPME) combined with one-dimensional gas chromatography-mass spectrometry (1D-GC-qMS). This approach allowed the definition of a volatile metabolite profile to each banana variety and can be used as pertinent criteria of differentiation. The investigated banana varieties (Dwarf Cavendish, Prata, Maçã, Ouro and Platano) have certified botanical origin and belong to the Musaceae family, the most common genomic group cultivated in Madeira Island (Portugal). The influence of dHS-SPME experimental factors, namely, fibre coating, extraction time and extraction temperature, on the equilibrium headspace analysis was investigated and optimised using univariate optimisation design. A total of 68 volatile organic metabolites (VOMs) were tentatively identified and used to profile the volatile composition in different banana cultivars, thus emphasising the sensitivity and applicability of SPME for establishment of the volatile metabolomic pattern of plant secondary metabolites. Ethyl esters were found to comprise the largest chemical class accounting 80.9%, 86.5%, 51.2%, 90.1% and 6.1% of total peak area for Dwarf Cavendish, Prata, Ouro, Maçã and Platano volatile fraction, respectively. Gas chromatographic peak areas were submitted to multivariate statistical analysis (principal component and stepwise linear discriminant analysis) in order to visualise clusters within samples and to detect the volatile metabolites able to differentiate banana cultivars. The application of the multivariate analysis on the VOMs data set resulted in predictive abilities of 90% as evaluated by the cross-validation procedure.


Chloro Derivatives of Isomers of a Giant Fullerene C104 : C104 (234)Cl16/18 , C104 (812)Cl12/24 , and C104 (811)Cl28.
The chemistry of a giant fullerene, C104 , has been extended by the synthesis and structural study of several chloro derivatives of three isolated pentagon rule (IPR) isomers of C104 nos. 234, 812, and 811. In the structure of C104 (234)Cl16/18 , two molecules with 16 and 18 attached Cl atoms occupy the same crystallographic site with an occupancy ratio of 61/39. The structures of C104 (812)Cl12 and C104 (812)Cl24 demonstrate substructure relationships of their chlorination patterns with single and double Cl attachments to 12 cage pentagons. The structure of C104 (811)Cl28 is compared with the known C104 (811)Cl24 thus revealing dramatic changes in the chlorination pattern, which occur with relatively small increases in the degree of chlorination.