[Spinal surgery in the elderly: does age have an influence on the complication rate?].
In accordance with the demographic trend, the number of elderly patients with spinal diseases which require surgery will increase continuously. Up to now, age has often been regarded as a contraindication for an elective operation. However, a review of the existing literature, the results of the European spine register "Spine Tango" and our own results show that the rate of complications after minimally invasive spinal surgery is as low in the elderly as it is in the younger population. But the higher the complexity of surgery, the higher the rate of complications with increasing age. However, even elderly (>65 years) and very elderly (>80 years) patients seem to benefit from surgical treatment, independent of the extent of spinal surgery. Because chronic pain leads to physical limitations, an impaired quality of life as well as a declined state of health, and because surgery can significantly improve these factors, even while remaining aware of the operational risks, age itself should not be considered as a contraindication for spinal surgery.


Impact of anastomotic leakage on long-term survival of patients undergoing curative resection for colorectal cancer.
The impact of anastomotic leakage on immediate postoperative mortality in patients undergoing potentially curative resection for colorectal cancer is well recognized. Its impact on long-term survival is less clear. The aim of the present study was to evaluate the relationship between anastomotic leakage and long-term survival in patients undergoing potentially curative resection for colorectal cancer. A total of 2235 patients who underwent potentially curative resection for colorectal cancer between 1991 and 1994 in Scotland were included in the study. Five-year survival rates and adjusted hazard ratios were calculated. Fourteen (16 per cent) of the 86 patients with an anastomotic leak died within 30 days of surgery compared with 83 (3.9 per cent) of 2149 without a leak. The 5-year cancer-specific survival rate, including postoperative deaths, was 42 per cent in patients with an anastomotic leak compared with 66.9 per cent in those with no leak (P < 0.001). Excluding postoperative deaths, respective values were 50 and 68.0 per cent (P < 0.001). The adjusted relative hazard ratios, for patients with an anastomotic leak compared with those without a leak, and excluding 30-day mortality, were 1.61 (95 per cent confidence interval (c.i.) 1.19 to 2.16; P = 0.002) for overall survival and 1.99 (95 per cent c.i. 1.42 to 2.79; P < 0.001) for cancer-specific survival. Development of an anastomotic leak is associated with worse long-term survival after potentially curative resection for colorectal cancer.


Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia.
Recent studies have indicated the beneficial effects of vascular endothelial growth factor (VEGF), and transplanted neural stem cells (NSCs) in cerebral ischemia. We investigated the effects of the combined administration of NSCs and VEGF on focal cerebral ischemia in adult rats. Four groups (n = 12, respectively)--group 1 (ischemia-only), group 2 (ischemia + VEGF), group 3 (ischemia + NSCs) and group 4 (ischemia + NSCs + VEGF)--were compared. Human NSCs (HB1.F3), labeled with Lac Z+ or PKH26, were given intravenously 24h after surgery (5 x 10(6) cells). At 48 h after surgery, recombinant human VEGF (50 microg/kg) was infused intravenously (1 microg/(kg min)). Behavioral tests using the modified limb placing and rotarod tests were performed every week following ischemia. Immunohistochemistry for endothelial barrier antigen (EBA), VEGF and Nissl staining were performed at day 35 after ischemia. Group 4 showed better behavioral recovery at 7, 14 and 28 days than group 3 (p = 0.020, 0.005 and 0.043, respectively). These functional recoveries were correlated with enhanced EBA immunoreactivities at day 35 after ischemia, especially in the ipsilesional striatum. Group 4 showed lesser degree of brain atrophy in cortex and striatum, when compared with other groups. The distribution of VEGF was not co-localized with NSCs. Our results suggest that VEGF may act synergistically on NSC-transplanted, ischemic brain via a pro-angiogenic effect.


Development and application of a multi-residue method for the determination of 53 pharmaceuticals in water, sediment, and suspended solids using liquid chromatography-tandem mass spectrometry.
Comprehensive source and fate studies of pharmaceuticals in the environment require analytical methods able to quantify a wide range of molecules over various therapeutic classes, in aqueous and solid matrices. Considering this need, the development of an analytical method to determine 53 pharmaceuticals in aqueous phase and in solid matrices using a combination of microwave-assisted extraction, solid phase extraction, and liquid chromatography coupled with tandem mass spectrometry is reported. Method was successfully validated regarding linearity, repeatability, and overall protocol recovery. Method detection limits (MDLs) do not exceed 1 ng L(-1) for 40 molecules in aqueous matrices (6 ng L(-1) for the 13 remaining), while subnanogram per gram MDLs were reached for 38 molecules in solid phase (29 ng g(-1) for the 15 remaining). Losses due to preparative steps were assessed for the 32 analytes associated to their labeled homologue, revealing an average loss of 40 % during reconcentration, the most altering step. Presence of analytes in wastewater treatment plant (WWTP) effluent aqueous phase and suspended solids (SS) as well as in river water, SS, and sediments was then investigated on a periurban river located in the suburbs of Bordeaux, France, revealing a major contribution of WWTP effluent to the river contamination. Sorption on river SS exceeded 5 % of total concentration for amitriptyline, fluoxetine, imipramine, ritonavir, sildenafil, and propranolol and appeared to be submitted to a seasonal influence. Sediment contamination was lower than the one of SS, organic carbon content, and sediment fine element proportion was accountable for the highest measured concentrations.


Non-malignant CSF lymphocytosis in a patient with acute lymphoblastic leukemia.
Patients with haematological malignancy are often profoundly immune suppressed, and more so if they require more than one line of therapy. Infection should always be considered when they become unwell. We discuss the differential diagnoses of a young man with multiply-relapsed Philadelphia chromosome-positive B-cell acute lymphoblastic leukaemia who presented with neurological symptoms and cerebrospinal fluid lymphocytosis. The diagnostic approach needs to be rapid and structured, and may require microbiology and neurology support.


A State Transition Model for Health Outcomes Associated with Vorapaxar Treatment as an Add-on to Standard Care Antiplatelet Therapy in the Prevention of Thrombotic Events for Patients with a Recent Myocardial Infarction.
The TRA 2°P-TIMI 50 trial showed the addition of vorapaxar to standard care (SC) antiplatelet therapy reduced the combined risk of death, myocardial infarction (MI), and stroke, while exhibiting an increase in moderate, but not other bleeding events. Our objective was to estimate the long-term health benefits and risks of vorapaxar as an add-on to SC treatment (lifetime aspirin and up to 12 months of clopidogrel) for patients with a prior MI and without a history of cerebrovascular disease. In the state transition model we developed, the patients transition between states due to recurrent MI, stroke, or death, and are at risk of non-fatal bleeding. Risk equations were developed from individual patient-level data from the TRA 2°P-TIMI 50 trial to predict long-term cardiovascular (CV) outcomes. Additional sources informed inputs for case fatality, bleeding rates on SC, risk of non-CV death, and utilities. Over a lifetime horizon, fewer CV events and more bleeding events occurred in the vorapaxar (VOR) + SC arm, relative to the SC-only arm. These results were ultimately accompanied by an increase in life expectancy and health benefits associated with add-on vorapaxar treatment, as the VOR + SC arm yielded an average of 8.27 discounted quality-adjusted life-years (QALYs) compared with an average of 7.96 discounted QALYs in the SC-only arm. This model framework leveraged novel risk equations to make long-term projections of CV events in a population at high risk of recurrence. Model results suggest vorapaxar is most effective as add-on therapy to SC antiplatelet treatment when initiated upon hospital discharge post-MI.


Determination of amantadine in human plasma by capillary gas chromatography using electron-capture detection following derivatization with pentafluorobenzoyl chloride.
A specific, sensitive, and accurate capillary gas chromatographic method for the quantitation of amantadine in human plasma is described. Amantadine and the internal standard, rimantadine were extracted from plasma under alkaline conditions into toluene. Both compounds were derivatized with pentafluorobenzoyl chloride. The derivatives were separated on a HP-1 capillary column at 180 degrees C and detected using a 63Ni electron-capture detector. The minimum quantifiable limit of the assay is 2.3 ng ml-1 of amantadine base using 1 ml of plasma. The method was used to evaluate the bioequivalence of two different formulations of amantadine hydrochloride.


Impact of Allergic Rhinitis and Asthma on COVID-19 Infection, Hospitalization, and Mortality.
It remains unclear if patients with allergic rhinitis (AR) and/or asthma are susceptible to corona virus disease 2019 (COVID-19) infection, severity, and mortality. To investigate the role of AR and/or asthma in COVID-19 infection, severity, and mortality, and assess whether long-term AR and/or asthma medications affected the outcomes of COVID-19. Demographic and clinical data of 70,557 adult participants completed SARS-CoV-2 testing between March 16 and December 31, 2020, in the UK Biobank were analyzed. The rates of COVID-19 infection, hospitalization, and mortality in relation to pre-existing AR and/or asthma were assessed based on adjusted generalized linear models. We further analyzed the impact of long-term AR and/or asthma medications on the risk of COVID-19 hospitalization and mortality. Patients with AR of all ages had lower positive rates of SARS-CoV-2 tests (relative risk [RR]: 0.75, 95% confidence interval [CI]: 0.69-0.81, P < .001), with lower susceptibility in males (RR: 0.74, 95% CI: 0.65-0.85, P < .001) than females (RR: 0.8, 95% CI: 0.72-0.9, P < .001). However, similar effects of asthma against COVID-19 hospitalization were only major in participants aged <65 (RR: 0.93, 95% CI: 0.86-1, P = .044) instead of elderlies. In contrast, patients with asthma tested positively had higher risk of hospitalization (RR: 1.42, 95% CI: 1.32-1.54, P < .001). Neither AR nor asthma had an impact on COVID-19 mortality. None of conventional medications for AR or asthma, for example, antihistamines, corticosteroids, or β2 adrenoceptor agonists, showed association with COVID-19 infection or severity. AR (all ages) and asthma (aged <65) act as protective factors against COVID-19 infection, whereas asthma increases risk for COVID-19 hospitalization. None of the long-term medications had a significant association with infection, severity, and mortality of COVID-19 among patients with AR and/or asthma.


A promiscuous T cell epitope-based HIV vaccine providing redundant population coverage of the HLA class II elicits broad, polyfunctional T cell responses in nonhuman primates.
Over the last few decades, several emerging or reemerging viral diseases with no readily available vaccines have ravaged the world. A platform to fastly generate vaccines inducing potent and durable neutralizing antibody and T cell responses is sorely needed. Bioinformatically identified epitope-based vaccines can focus on immunodominant T cell epitopes and induce more potent immune responses than a whole antigen vaccine and may be deployed more rapidly and less costly than whole-gene vaccines. Increasing evidence has shown the importance of the CD4+ T cell response in protection against HIV and other viral infections. The previously described DNA vaccine HIVBr18 encodes 18 conserved, promiscuous epitopes binding to multiple HLA-DR-binding HIV epitopes amply recognized by HIV-1-infected patients. HIVBr18 elicited broad, polyfunctional, and durable CD4+and CD8+ T cell responses in BALB/c and mice transgenic to HLA class II alleles, showing cross-species promiscuity. To fully delineate the promiscuity of the HLA class II vaccine epitopes, we assessed their binding to 34 human class II (HLA-DR, DQ, and -DP) molecules, and immunized nonhuman primates. Results ascertained redundant 100% coverage of the human population for multiple peptides. We then immunized Rhesus macaques with HIVBr18 under in vivo electroporation. The immunization induced strong, predominantly polyfunctional CD4+ T cell responses in all animals to 13 out of the 18 epitopes; T cells from each animal recognized 7-11 epitopes. Our results provide a preliminary proof of concept that immunization with a vaccine encoding epitopes with high and redundant coverage of the human population can elicit potent T cell responses to multiple epitopes, across species and MHC barriers. This approach may facilitate the rapid deployment of immunogens eliciting cellular immunity against emerging infectious diseases, such as COVID-19.


Effect of cisapride on esophageal pH monitoring in children with reflux-associated bronchopulmonary disease.
Clinical evaluation and prolonged esophageal pH monitoring were performed before and during treatment with cisapride (0.3 mg/kg t.i.d.) for 1 month in 19 children with reflux-associated bronchopulmonary disease. Results (mean +/- SEM) show that cisapride significantly decreases the frequency of long duration (greater than 5 min) reflux episodes (from 9.7 +/- 0.7 to 5.7 +/- 1.2), the percentage of total time pH was less than 4 (from 15.9 +/- 2.5 to 7.7 +/- 1.1%), the percentage of time pH was less than 4 at night (from 18.0 +/- 3.9 to 4.9 +/- 1.5%), the duration of the longest reflux episodes (from 44.5 +/- 6.4 to 19.7 +/- 2.7 min), as well as the duration of reflux at night (from 100.1 +/- 28.0 to 28.2 +/- 10.1 min). The frequency of reflux episodes, however, remains unaffected by cisapride. Cough fits at night disappeared completely in 12 out of 13 children. We conclude that cisapride given for 1 month significantly decreased gastroesophageal reflux as well as cough episodes at night.


Enumeration takes time: Accuracy improves even after stimuli disappear.
Numerical cognition is widespread among animal species and present from birth in humans. Laboratory studies show that longer stimulus duration improves numerical discrimination accuracy (Inglis & Gilmore, 2013; Wood & Spelke, 2005). Inglis and Gilmore (2013) suggested that longer durations allow subjects to resample the stimulus image multiple times, resulting in a more accurate final estimate. The current study tested this "multiple sampling" model alongside two competing models - "serial foveal accumulator" (Cheyette & Piantadosi, 2019) and "longer processing time" - to determine how stimulus duration relates to accuracy. Adult subjects completed a fully within-subject, 2AFC task in which they judged which of two arrays had more dots; accuracy was the dependent measure. Experiment 1 revealed higher accuracy in the 500 ms stimulus duration condition compared to the 100 ms condition, replicating previous results. Experiments 2 and 4 extended this finding. When stimulus duration was held constant at 100 ms, adding a 400 ms delay between stimulus offset and mask onset improved accuracy. Accuracy was similar in the 500 ms stimulus duration condition (E1) and the 100 ms duration + 400 ms mask delay conditions (E2 and E4), indicating that post-stimulus processing time improves accuracy, rather than stimulus duration per se. This contrasts with both the multiple sampling model and the serial foveal model, although we cannot exclude the possibility that sampling continues in iconic memory. Numerosity was a significant factor in all four experiments, suggesting a serial component in the enumeration process. These findings shed light on the cognitive processes underlying nonverbal number representation in humans.


Genomic ancestry, diet and microbiomes of Upper Palaeolithic hunter-gatherers from San Teodoro cave.
Recent improvements in the analysis of ancient biomolecules from human remains and associated dental calculus have provided new insights into the prehistoric diet and genetic diversity of our species. Here we present a multi-omics study, integrating metagenomic and proteomic analyses of dental calculus, and human ancient DNA analysis of the petrous bones of two post-Last Glacial Maximum (LGM) individuals from San Teodoro cave (Italy), to reconstruct their lifestyle and the post-LGM resettlement of Europe. Our analyses show genetic homogeneity in Sicily during the Palaeolithic, representing a hitherto unknown Italian genetic lineage within the previously identified Villabruna cluster. We argue that this lineage took refuge in Italy during the LGM, followed by a subsequent spread to central-western Europe. Analysis of dental calculus showed a diet rich in animal proteins which is also reflected on the oral microbiome composition. Our results demonstrate the power of this approach in the study of prehistoric humans and will enable future research to reach a more holistic understanding of the population dynamics and ecology.


Heterophile antibodies. Part II. An evaluation of the effect of autologous blood group substances on the natural formation of agglutinating antibodies to sheep red blood cells.
This study shows that some substances in human secretions can inhibit the agglutination of sheep red blood cells by human antibodies. When present in adequate concentrations, they can also inhibit the reaction of the donor's own sheep red blood cell antibody activity in vito. The subjects in whom this phenomenon was found almost always had low agglutinating antibody titers to sheep red blood cells. The inhibiting activity of saliva for sheep red blood cell antibodies was influenced by the ABH secretor status. Substances reacting against sheep red blood cell antibodies occur in the secretions in considerably smaller quantities than ABH substances.


PET assessment of acute gastrointestinal graft versus host disease.
Acute gastrointestinal graft versus host disease (GI-GVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT), and is characterised by severe morbidity, frequent treatment-refractoriness, and high mortality. Early, accurate identification of GI-GVHD could allow for therapeutic interventions to ameliorate its severity, improve response rates and survival; however, standard endoscopic biopsy is inadequately informative in terms of diagnostic sensitivity or outcome prediction. In an era where rapid technological and laboratory advances have dramatically expanded our understanding of GI-GVHD biology and potential therapeutic targets, there is substantial scope for novel investigations that can precisely guide GI-GVHD management. In particular, the combination of tissue-based biomarker assessment (plasma cytokines, faecal microbiome) and molecular imaging by positron emission tomography (PET) offers the potential for non-invasive, real-time in vivo assessment of donor:recipient immune activity within the GI tract for GI-GVHD prediction or diagnosis. In this article, we review the evidence regarding GI-GVHD diagnosis, and examine the potential roles and translational opportunities posed by these novel diagnostic tools, with a focus on the evolving role of PET.


Modulation of lymphoproliferation by human growth hormone.
This study was designed to investigate the capacity of human growth hormone (hGH) to induce proliferation of human peripheral blood lymphocytes (PBL) and its effect on lectin-induced lymphoproliferation, as measured by [3H]-thymidine (3H-TdR) incorporation into lymphocyte DNA. We observed that hGH itself induced lymphoproliferation. Maximal responses were reached with 50 ng/ml after 4 days and 25 ng/ml after 7 days. Anti-hGH-antiserum completely blocked the stimulatory capacity of hGH. Further evidence for the specificity of the effect was obtained by the finding that no other hormone present in the hGH preparation produced any effect on lymphocyte cultures. In contrast to its stimulatory capacity, hGH reduced the proliferative response of PBL to phytohaemagglutinin (PHA). This effect was also neutralized by anti-hgH-antiserum. These results show a direct stimulatory effect of hGH on PBL and a regulatory effect of the hormone on lectin-induced lymphoproliferation.


Management of Scapular Tumors.
Scapular resections are large oncologic undertakings. Due to the soft tissue coverage of the scapula, tumors are often able to be resected with a negative margin. Involvement of the brachial plexus and axillary vessels is rare, allowing for a limb-salvage surgery in most cases. Functional outcomes are based on the magnitude of resection; patients undergoing a partial scapulectomy and those with glenoid preservation demonstrate improved outcomes compared to patients undergoing a total scapulectomy or glenoid resection. Although scapular endoprosthetics are available, there is limited data to support their routine use.


Chromosomal location of genomic SSR markers associated with yellow rust resistance in Turkish bread wheat (Triticum aestivum L.).
We have previously reported Xgwm382 as a diagnostic marker for disease resistance against yellow rust in Izgi2001 x ES14 F2 population. Among the same earlier tested 230 primers, one SSR marker (Xgwm311) also amplified a fragment which is present in the resistant parent and in the resistant bulks, but absent in the susceptible parent and in the susceptible bulks. To understand the chromosome group location of these diagnostic markers, Xgwm382 and Xgwm311, in the same population, we selected 16 SSR markers mapped only in one genome of chromosome group 2 around 1-21 cM distance to these diagnostic markers based on the SSR consensus map of wheat. Out of 16 SSRs, Xwmc658 identified resistant F2 individuals as a diagnostic marker for yellow rust disease and provided the location of Xgwm382 and Xgwm311 on chromosome 2AL in our plant material.


Noninvasive detection of left ventricular systolic dysfunction by acoustic cardiography in cardiac failure patients.
Despite its shortcomings, ejection fraction (EF) is widely used to detect left ventricular systolic dysfunction (LVSD) as has prolonged QRS duration as indirect evidence of LVSD. However, acoustic cardiography provides other parameters for detecting LVSD without these limitations. One parameter, the electromechanical activation time (EMAT), is prolonged in LVSD. We compared the abilities of acoustic cardiography, EF, and QRS duration to detect LVSD. We studied a sample of 108 patients who underwent elective diagnostic cardiac catheterization. The diagnostic findings included left ventricular filling pressures, angiographic EF, and maximum left ventricular dP/dt. We defined LVSD as a maximum left ventricular dP/dt of <1600 mm Hg/s. At thresholds of 35% and 50% to detect LVSD, the sensitivities of angiographic EF were 39% and 74%; specificities were 89% and 70%, respectively. At QRS duration thresholds of 100 and 120 ms, sensitivities were 63% and 35%; specificities, 63% and 89%, respectively. At thresholds of 100 and 110 ms, EMAT had sensitivities of 53% and 42%, and specificities of 90% and 100%, respectively. EMAT performed better than LV EF or QRS duration in hemodynamic subgroups. Acoustic cardiography is a convenient, automated diagnostic method whose performance for detecting LVSD exceeds both angiographic EF and QRS duration alone.


MitoVisualize: a resource for analysis of variants in human mitochondrial RNAs and DNA.
We present MitoVisualize, a new tool for analysis of the human mitochondrial DNA (mtDNA). MitoVisualize enables visualization of: (i) the position and effect of variants in mitochondrial transfer RNA and ribosomal RNA secondary structures alongside curated variant annotations, (ii) data across RNA structures, such as to show all positions with disease-associated variants or with post-transcriptional modifications and (iii) the position of a base, gene or region in the circular mtDNA map, such as to show the location of a large deletion. All visualizations can be easily downloaded as figures for reuse. MitoVisualize can be useful for anyone interested in exploring mtDNA variation, though is designed to facilitate mtDNA variant interpretation in particular. MitoVisualize can be accessed via https://www.mitovisualize.org/. The source code is available at https://github.com/leklab/mito_visualize/. Supplementary data are available at Bioinformatics online.


Heterotropic cooperativity between putative recognition sites for progesterone metabolites and the atypical benzodiazepine Ro 5-4864.
The binding of the cage convulsant t-butylbicyclophosphorothionate (TBPS) and 36Cl- uptake by synaptoneurosomes were used to test the ability of progesterone metabolites to modulate allosterically the Ro 5-4864 (4'-chlorodiazepam) binding site that is functionally coupled to the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex (GBRC) in rat brain. Dose-dependent enhancement of [35S]TBPS binding by Ro 5-4864 occurs in rat cerebral cortex in the presence of the progesterone metabolites 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) and 5 alpha-pregnan-3 alpha, 20 alpha-diol (pregnanediol). The pregnanediol effect is completely GABA dependent, whereas that of 3 alpha-OH-DHP is not. Conversely, Ro 5-4864 opposed the action of 3 alpha-OH-DHP by increasing the IC50 for 3 alpha-OH-DHP inhibition of [35S]TBPS binding. In cortical synaptoneurosomes, Ro 5-4864 antagonized both 3 alpha-OH-DHP and pregnanediol enhancement of GABA-stimulated 36Cl- uptake. In both binding and functional studies, pregnanediol showed limited efficacy relative to 3 alpha-OH-DHP, as previously reported. These findings provide the initial evidence that the GBRC-linked Ro 5-4864 binding site is allosterically coupled to the putative progesterone metabolite recognition site and confirm the GABA-mimetic properties of 3 alpha-OH-DHP and pregnanediol.


Structural equation modeling of the relationship between nursing students' quality of life and academic resilience.
Across the Middle Eastern countries, there is a lack of studies exploring the connection between the quality of life (QoL) and academic resilience of nursing students. This study determines the association between nursing students' profile variables and their QoL and academic resilience (AR). A descriptive cross-sectional design with structural equation modeling (SEM) was adopted. This study was conducted at the College of Nursing at the University of Ha'il, KSA. Survey questionnaires using the 12-item Brunnsviken Brief Quality of Life Scale (BBQ) and 30-item Academic Resilience Scale (ARS-30) were utilised to collect data from nursing students (n = 384). SEM via latent variable analysis (lavaan) software version 0.6-7 was used for statistical derivation and analysis. SEM revealed no correlation with QoL and AR when compared using the participants' profile variables (gender, year level, and enrolled units). There was a correlation between the grade point average (GPA) and QoL. However, no association was found between QoL and AR. GPA exhibited a positive correlation with QoL; thus, nursing students with higher GPA have a more stable and desirable QoL. Additionally, our findings illustrate the individuality of nursing students despite their shared characteristics.


Protective activities of ribosomal ribonucleic acid and lipopolysaccharide of Pseudomonas aeruginosa: a comparative study.
Ribosomal ribonucleic acid (RNA) and lipopolysaccharide (LPS) from P. aeruginosa were compared with respect to their protective activities in mice against an infection with P. aeruginosa. This study is concentrated on the protective activity of RNA. RNA isolated from purified ribosomes did not contain LPS as determined with the Limulus test. Injection of RNA with the adjuvant dimethyldioctadecylammonium bromide (DDA) protected mice against P. aeruginosa without inducing LPS-specific antibodies. C3H/HeJ mice which are relatively insensitive to the protective activity of LPS could be protected with RNA. The protective activities of RNA and LPS from a mutant strain of P. aeruginosa, PAC 605, containing defective lipopolysaccharide, were compared with the protective activities of RNA and LPS from the parent strain, PAC IR. The protective activity of LPS from PAC 605 was 1000 fold lower than the protective activity of LPS from PAC IR. RNA preparations of both strains induced similar percentages of survival. The protective activity of ribosomal RNA from P. aeruginosa was nonspecific since mice were also protected against a heterologous serotype of P. aeruginosa and against Escherichia coli. RNA from ribosomes of P. aeruginosa, E. coli and the non-lipopolysaccharide containing Saccharomyces cerevisiae had similar protective activities. No protection was obtained with the ribonucleic acid from the E. coli phage MS2. It is concluded that ribosomal RNA has protective activities distinct from those of LPS.


Evaluation of bitter compounds in Zanthoxylum schinifolium Sieb. et Zucc. by instrumental and sensory analyses.
As a common food seasoning in China, Zanthoxylum schinifolium Sieb. et Zucc. is desired by consumers for its special aroma; however, its bitter taste has a negative economic impact on the food industry. In this study, untargeted metabolomics was used to perform full-coverage detection of metabolites in Z. schinifolium Sieb. et Zucc. A total of 53 potential bitter metabolites were screened. Additionally, key bitter compounds were concentrated using sensory-guided fractionation technique and subsequently characterized by UPLC-Q-TOF-MS, and a total of 13 bitter compounds were obtained. Then, dose over threshold values (DOT) of these 13 compounds were calculated, showing that 11 compounds significantly contribute to the bitterness of Z. schinifolium Sieb. et Zucc., with quercetin, isorhamnetin and kaempferol have particularly low thresholds and high contents. This study is the first to comprehensively define the bitter substances in Z. schinifolium Sieb. et Zucc., providing a reliable theoretical basis for future research on bitterness mechanisms.


[Possibilities of sonographic image fusion: Current developments].
For diagnostic and interventional procedures ultrasound (US) image fusion can be used as a complementary imaging technique. Image fusion has the advantage of real time imaging and can be combined with other cross-sectional imaging techniques. With the introduction of US contrast agents sonography and image fusion have gained more importance in the detection and characterization of liver lesions. Fusion of US images with computed tomography (CT) or magnetic resonance imaging (MRI) facilitates the diagnostics and postinterventional therapy control. In addition to the primary application of image fusion in the diagnosis and treatment of liver lesions, there are more useful indications for contrast-enhanced US (CEUS) in routine clinical diagnostic procedures, such as intraoperative US (IOUS), vascular imaging and diagnostics of other organs, such as the kidneys and prostate gland.


Changing dynamics of drug overdoses in the United Kingdom: An attempt to replicate the Jalal et al. findings of steady exponential growth.
Jalal et al. discovered that between 1979 and 2020 total rates and counts of fatal drug overdoses in the United States exhibited exponential growth at a very steady rate even though deaths from individual drugs did not. That is a startling result because it means that the different drugs are in effect "taking turns", with one growing faster just as another drug's death rate growth ebbs. That raises the question of whether this steadiness in the all-drug death rates is in some sense just a coincidence peculiar to the United States or whether it might reflect some more general phenomenon and so manifest in other countries. We fit the same model used by Jalal et al. to data on drug-related death rates for the countries of the United Kingdom. The main finding is largely a failure to replicate the United States result. Simple graphical display of the trends and a number of statistical measures show that the growth in the United Kingdom was not only slower than in the United States, it was also less steady, with the exception of Northern Ireland. Steady exponential growth in the all-drugs mortality rate may be a phenomenon specific to certain contexts. It remains an open question whether the explanation of steady exponential growth in the United States and Northern Ireland relates to demand and supply mechanisms, to social and political conditions, or to coincidence.


Vestibular and cochlear nerve enhancement on MRI and its correlation with vestibulocochlear functional deficits in patients with Ramsay Hunt syndrome.
The correlation between enhancement of the vestibulocochlear nerves on gadolinium-enhanced magnetic resonance imaging (MRI) and vestibulocochlear functional deficits was examined in patients with Ramsay Hunt syndrome (RHS). Nineteen patients with RHS who showed herpes zoster oticus, peripheral facial palsy, and vertigo were enrolled. Canal paresis (CP) in the caloric test, abnormal response to ocular and cervical vestibular myogenic potentials (oVEMP and cVEMP), and refractory sensorineural hearing loss were evaluated. MRI images perpendicular to the internal auditory canal were reconstructed to identify the superior (SVN) and inferior vestibular nerves (IVN) and the cochlear nerve (CV). The signal intensity increase (SIinc) of the four-nerve enhancement was calculated as an index. Among RHS patients, 79%, 53%, 17% and 26% showed CP in the caloric test, abnormal responses to oVEMP and cVEMP, and refractory sensorineural hearing loss, respectively. SIinc rates of the SVN were significantly increased in RHS patients with CP in the caloric test, and with abnormal responses to oVEMP and cVEMP. SIinc rates of the SVN tended to increase in RHS patients with refractory sensorineural hearing loss (p = 0.052). SIinc rates of the IVN were significantly increased in RHS patients with abnormal responses to oVEMP and cVEMP, and refractory sensorineural hearing loss, but not in those with CP in the caloric test. SIinc rates of the CN were significantly increased in RHS patients with CP in the caloric test, abnormal response to oVEMP and refractory sensorineural hearing loss, but not in those with abnormal response to cVEMP. In patients with RHS, the origin of vertigo may be superior vestibular neuritis, which is affected by reactive varicella-zoster virus from the geniculate ganglion of the facial nerve through the faciovestibular anastomosis. The results also suggested that in some RHS patients, inferior vestibular neuritis contributes to the development of vertigo and that the origin of refractory sensorineural hearing loss is cochlear neuritis.


Cyclic AMP and free fatty acids in the longer-term regulation of pyruvate dehydrogenase kinase in rat soleus muscle.
Starvation increased pyruvate dehydrogenase (PDH) kinase activity in extracts of freshly excised rat soleus 2.2-fold (from 0.6 min-1 in fed rats to 1.31 min-1 in 48-h-starved rats). In fed rats, activities were unchanged following 24 h of culture in medium 199, but increased 2.1-fold on 24 h of culture with 50 microM dibutyryl cAMP plus 1 mM n-octanoate and 1.6-1.7-fold with either agent alone. Approx. 70% of the increase in PDH kinase induced by starvation was lost following 24 h of culture in medium 199; the loss was prevented by 50 microM dibutyryl cAMP plus 1 mM n-octanoate. cAMP concentrations in fresh soleus muscle were 1 nmol/g (fed rats) and 1.6 nmol/g (starved rats). After 20-60 min of culture the fed-starved difference disappeared and [cAMP] fell to 0.4 nmol/g. Calcitonin-gene-related peptide (CGRP) increased cAMP 3-fold; the increase was maintained throughout 24 h of culture, but was readily reversed at 30 min or 24 h of culture by 60-min incubation with CGRP-free medium. Starvation of the rat (48 h) had no effect on the sensitivity of soleus towards the [cAMP]-increasing effect of CGRP. It is concluded that culture may reverse effects of starvation on PDH kinase activity by lowering cAMP and by removal from the in vivo effects of circulating free fatty acids; and that starvation and CGRP had no detectable long-term effects on the cAMP system in soleus muscle.


An investigation into the impact of approaches to learning on final-year student nurses' clinical decision-making.
This research aimed to investigate whether a correlation exists between students' approach to learning and clinical decision-making and to determine whether an educational learning intervention would impact on clinical decision-making outcomes. Tait, Entwistle and McCune's Approaches to Study Skills for Students (ASSIST) and Jenkins' Clinical Decision Making Nursing Scale (CDMNS) was administered to a convenience sample of adult nursing students (n = 78) at a university in central London, UK, at the beginning of the final year of their nursing course and, following the learning intervention, again at the end of the year. Pre-intervention, 38% of participants predisposed to the surface approach to learning; post-intervention, less than 8%. Clinical decision-making scores were statistically significantly higher for students adopting the strategic approach at the pre-intervention point and significantly higher for those adopting the deep approach at the post-intervention point. At both pre- and post- intervention data collection points there was a negative correlation between the surface approach and clinical decision-making scores. Findings indicate a statistically significant relationship exists between participants' approach to learning and their clinical decision-making. Changing from the surface to either the strategic or deep approach to learning is shown to impact positively on clinical decision-making outcomes.


Meiosis in two human reciprocal translocations.
Analysis of meiotic chromosomes from two human male translocation heterozygotes is reported. One had total sterility after maturation arrest and chain configurations at meiosis, and the second had a abnormal children who were presumed to be genetically unbalanced.


Computer-assisted reading of DNA sequences.
DNA sequencing is increasingly used in a range of medical activities involving DNA diagnostics and research. This is the result of improving technology and cheaper costs. Paradoxically, a greater demand for DNA sequencing has placed additional work on the laboratory because sequencing profiles must be checked visually despite the availability of informatics-based tools in interpreting DNA sequence traces. In this environment it is essential to have more sophisticated software that will allow the sites of known and unknown DNA variants to be quickly identified, as well as providing an objective assessment of quality for the DNA sequence generated. This chapter describes the Applied Biosystems SeqScape software program (version 2.5) and how it has assisted in the interpretation of DNA sequencing in a DNA diagnostic laboratory.


Alterations in retinal neurotransmitter receptors and neuropeptides of the chick by kainic acid and acrylamide.
The effects of intraocular injection of kainic acid and acrylamide upon retinal neuropeptides and high affinity binding sites have been determined in the chick. Kainic acid causes a sharp reduction in Met-enkephalin and somatostatin while neurotensin levels are unchanged. This treatment also lowers the extent of cholinergic muscarinic but not of [3H]naloxone or [3H]spiroperidol binding. In contrast, acrylamide treatment causes major increases of retinal Met-enkephalin and neurotensin concentrations. The binding of [3H]naloxone is also increased, and no reductions of any peptide or binding intensity were observed. The results indicate the plasticity of retinal neuropeptide levels and the selectivity with which these can be modulated.


The functional role of longitudinal, circumferential, and radial myocardial deformation for regulating the early impairment of left ventricular contraction and relaxation in patients with cardiovascular risk factors: a study with two-dimensional strain imaging.
Two-dimensional strain imaging allows rapid and accurate analysis of regional left ventricular (LV) systolic and diastolic mechanics in the longitudinal, radial, and circumferential directions. The aim of this study was to assess precisely the differences in early impairment of LV myocardial contraction and relaxation among the 3 directions in 70 patients with cardiovascular risk factors and preserved LV pump function. The patients were classified into 2 groups according to the ratio of early diastolic to atrial systolic velocity (E/A) of transmitral flow: E/A > or = 1 (n = 35, 57 +/- 6.8 years) or E/A < 1 (n = 35, 60 +/- 4.9 years). The longitudinal strain and strain rate curves were determined in apical 2- and 4-chamber views, and radial and circumferential strain and strain rate curves and LV torsion curve were determined in the parasternal short-axis views. The mean peak systolic longitudinal strain and strain rate were lower, whereas the mean peak systolic circumferential strain and strain rate were greater in the E/A < 1 group. There were no significant differences in the mean peak systolic radial strain and strain rate between the 2 groups. The mean peak early diastolic longitudinal strain rate was markedly lower in the E/A < 1 group. The mean peak LV strain rates during atrial systole in all 3 directions were greater in the E/A < 1 group. The mean peak LV systolic longitudinal strain and longitudinal strain rate during atrial systole were independent predictors related to E/A in all patients. There were no significant differences in torsion and torsional and untwisting rates between the 2 groups. LV myocardial contraction and relaxation were first impaired in the longitudinal direction among the 3 directions in subclinical patients with cardiovascular risk factors. However, LV pump function and LV filling were compensated by circumferential shortening at ventricular systole and 3 directional lengthenings at atrial systole, respectively.


Actions taken by the European commission to address the safety of sunbeds.
The safety of sunbed, especially when it comes to protecting young and vulnerable consumers, is a key concern that the Directorate-General for Health and Consumers has been trying to address in various ways. This document presents a brief overview of activities undertaken at European level to address the main concerns related to the use of this product.


Low melting Li/K/Cs acetate salt mixtures as new ionic media for catalytic applications--first physico-chemical characterization.
In order to expand the temperature limits of Supported Ionic Liquid Phase (SILP) or Solid Catalyst with Ionic Liquid Layer (SCILL) systems to higher operation temperatures, the mixture of lithium acetate, potassium acetate, and caesium acetate (molar ratio of 0.2/0.275/0.525) has been studied in detail. Physico-chemical properties of the bulk melt are reported together with stability data of the modern salt on various solid support materials showing attractive properties for many potential high temperature applications.


Characterization of avian thymic hormone and chicken parvalbumin 3 target cells.
Avian thymic hormone (ATH) is a β-parvalbumin produced by epithelial cells in the thymic cortex and in the eyes of chickens. Chicken parvalbumin 3 (CPV3) is a homologous protein produced in the thymus and in hair cells of the chicken ear. ATH circulates in the blood on a five-day cycle and stimulates cell-mediated immunity when administered to young chickens. We report the identification of target cells for ATH and CPV3 and the immunophenotype of target cells for ATH. Newly hatched chicks were injected intracoelomically with ATH and killed 5, 10, 15 or 20 min later. Naïve chickens also were killed at 1, 7 and 14 days of age. Various tissues were examined by EM for the presence of either ATH or CPV3 using colloidal gold labeling. Gold particles were initially present on plasma membranes of lymphocytes in T cell areas of spleen and cecal tonsils from the chicks injected with ATH, internalized within 10 min, and accumulated in nuclei by 20 min. Immunofluorescence staining also identified the presence of ATH in T cell areas of spleen and cecal tonsils. Target cells labeled for ATH were immunophenotyped by double labeling. They were positive for CD3, CD8 and the lymphocyte receptor TCR-1, a phenotype characteristic of cytotoxic γδ T cells. Some of the target cells in the spleen were TCR-3 positive. Targeting of lymphocytes by CPV3 indicated that it may also be an immunomodulating hormone.


Polydatin ameliorates diabetic cardiomyopathy via Sirt3 activation.
Diabetic cardiomyopathy is identified as cardiac ventricular dysfunction induced by an insulin shortage in diabetic patients. Our previous studies have shown that Polydatin (PD) alleviates cardiac dysfunction after myocardial infarction (MI) injury. Nevertheless, the mechanism by which PD regulates diabetic cardiomyopathy has not been reported. In this study, we demonstrated the effects and described the mechanisms of PD in diabetic cardiomyopathy in both adult mouse hearts and neonatal mouse cardiomyocytes. We injected streptozotocin (STZ) to induce the DM model in wild-type (WT) and Sirt3 knockout (Sirt3-/-) mice. Mitochondrial bioenergetics in diabetic mice were detected by measuring citrate synthase activity and ATP content. The extent of autophagy regulation by PD was investigated by detecting the levels of Beclin 1, Atg5, LC3 and p62. Compared to the WT mouse hearts, hearts from the diabetic mice exhibited better cardiac function and a higher level of autophagy. Moreover, mitochondrial function in the diabetic mouse hearts was improved after PD treatment. However, PD treatment had no effect on the Sirt3 knockout diabetic mouse hearts. Additionally, PD increased autophagy flux in the cardiomyocytes that were cultured in high-glucose medium for 48 h. In addition, PD had no effects on the cardiomyocytes under high-glucose conditions when we down-regulated Sirt3. Altogether, PD attenuated cardiac dysfunction, increased autophagy flux and improved mitochondrial bioenergetics by up-regulating Sirt3 in the diabetic mice.


CardioWest total artificial heart: Bad Oeynhausen experience.
The use of ventricular assist devices (VAD) has become a widely accepted therapeutic option. However, there are still limitations to the patient collective eligible for VAD placement, who might therefore benefit from the implantation of a total artificial heart. We present the first German single-center experience with the CardioWest total artificial heart (TAH) (SynCardia Systems, Tucson, AZ) in 42 patients. Between February 2001 and December 2003, 42 patients (37 men, 5 women, mean age 51 +/- 13 years) received a TAH at our Center. Their body surface area ranged between 1.5 and 2.4 (mean, 1.9 +/- 0.19) m2. All patients were in persistent cardiogenic shock in spite of maximum inotropic support and had numerous preoperative risk factors (intraaortic balloon pumping, mechanical ventilation, acute renal failure, previous cardiac surgery, recent cardiopulmonary resuscitation). Duration of support was 1 to 291 days. Eleven patients (26%) underwent successful transplantation; 9 of them could be discharged home. Twenty-two patients died under support, 21 of them from multiple organ failure and 1 patient from a technical problem. Nine patients are still on the device, 4 of them at home after the original CardioWest console was replaced by the Berlin Heart EXCOR driver (Berlin Heart, Berlin, Germany). Exceptional results were achieved in patients with cardiogenic shock after cardiac surgery or after acute myocardial infarction. Against the background of the extremely poor preoperative situation of our patients, the overall survival rate of 48% can be considered as favorable. A prospective, randomized study is planned to find out whether patients with idiopathic dilated or ischemic cardiomyopathy are more likely to benefit from a biventricular assist device or a total artificial heart.


Evaluating the cytotoxicity of flaxseed orbitides for potential cancer treatment.
Flaxseed as well as its oil component possess antitumor activities against different types of cancer and have been used by some patients as complementary and/or alternative medicine. Linoorbitides (LOBs) are one family of flaxseed compounds that has implications for anticancer and antioxidant activity. The cytotoxicity of [1-9-NαC]-linusorb-B3 (LOB3), [1-9-NαC]-linusorb-B2 (LOB2), [1-9-NαC],[1-Rs,Ss-MetO]-linusorb-B2 ([MetO]-LOB2) and [1-8-NαC],[1-Rs,Ss-MetO]-linusorb-B1 ([MetO]-LOB1) was measured against human breast cancer Sk-Br-3 and MCF7 cell lines and melanoma A375 cell line. Overall cytotoxicity is cell-type specific. It scales as the hydrophobicity and concentration of the LOBs with the most abundant LOB3 being the most cytotoxic. Oral administration of LOB3 as a potential therapeutic agent might not be applicable as a much too high and/or frequent dose would be required to achieve a serum concentration of 400-500 μg/mL due to bioavailability and pharmacokinetic factors. However, LOB3 may be suitable for topical treatment formulations or as a lead compound in developing anticancer LOB derivatives.


The activation of porcine pancreatic phospholipase A2 by dipalmitoylphosphatidylcholine large unilamellar vesicles. Analysis of the state of aggregation of the activated enzyme.
Previous work from this laboratory and others has shown that the hydrolysis of pure dipalmitoylphosphatidylcholine (DPPC) liposomes by porcine pancreatic phospholipase A2 in the vicinity of the gel-to-liquid crystal phase transition is characterized by a slow initial phase followed by an apparent burst of activity. In this article we report a detailed quantitative analysis of the early time course of the hydrolysis of dipalmitoylphosphatidylcholine large unilamellar vesicles at 38 degrees C. Several kinetic models to quantitatively describe the data were considered. The most conservative model consistent with the kinetic data is one in which the enzyme initially binds the bilayer and becomes activated via a process that requires the formation of protein dimers on the surface of the membrane. The relevant kinetic parameters of the model are reported.


Tonic vibration reflex and muscle afferent block in writer's cramp.
Patients with focal dystonia take advantage of certain cutaneous or proprioceptive sensory inputs to alleviate their symptoms ("sensory trick"). We examined the effects of increasing muscle spindle activity by the tonic vibration reflex maneuver and decreasing it by intramuscular injection of lidocaine. The vibration was applied to the palm or the tendon of forearm muscles in 15 patients with writer's cramp and 15 age-matched normal subjects. In 11 patients, the vibration induced dystonic postures or movements typical of those seen during writing. Normal subjects showed either no response to the vibration or a gradually developing tonic vibration reflex only in the wrist and finger flexors, which produced visible movements with a significantly longer latency (12.5 +/- 6.7 seconds [mean +/- standard deviation]) than what was observed in the patients (2.7 +/- 2.5 seconds, p < 0.0001). Local injection of lidocaine (0.5%, 5-40 ml/muscle) attenuated the tendon reflex with relatively little effect on the M response. Injection into muscles with increased activity produced marked reduction of dystonic movements and significant clinical improvement in 13 patients, whereas injection into the other muscles had no effect. The clinical benefit lasted for 1 to 24 hours after injection. In 13 patients who had additional injections of 10% ethanol, which blocks sodium channels for a longer period than does lidocaine, the duration of action was prolonged to 5 to 21 days. These findings suggest that muscles causing dystonic movements have abnormal sensitivities to vibration at rest and that muscle afferents may play a pivotal role in producing dystonic movements.(ABSTRACT TRUNCATED AT 250 WORDS)


Evidence that revascularization by ventricular-internal mammary artery implants increases longevity. Twenty-four year, nine month follow-up.
Revascularization of the heart is a means of relieving symptoms of coronary artery disease--such as angina, fatigue, and dyspnea. The question of whether revascularization prolongs the life of the patient has been debated. My colleagues and I have reviewed our years of experience with patients treated by implantation of internal mammary arteries into the ventricles. We have compared our series with other groups of patients treated medically. Our conclusion is that revascularization via internal mammary artery implants does increase longevity.


Carcass chilling method effects on color and tenderness of bison meat.
Carcasses were conventionally (C, n = 9) or vascularly chilled using the Rinse & Chill® process (RC; n = 9). Muscles (Longissimus lumborum, LL; Triceps brachii, TB) were processed (LL, steaks; TB, ground), packaged (polyvinyl chloride, PVC; vacuum, VAC), and displayed or stored dark. Measurements included color, purge, pH, sarcomere length, shear force, and cooking loss. Data were analyzed as a split plot design with carcass chilling treatment as whole plot and display day as split plot. Data were analyzed separately by packaging method. RC increased (P < .05) cooking loss 1.7% but decreased shear force 24% (C, 42.5 N; P < .05) in steaks. RC ground bison packaged in PVC and VAC had greater (P < .05) CIE L*, a*, and b* values than C. RC VAC bison steaks had greater (P < .05) oxymyoglobin, deoxymyoglobin and decreased (P < .05) metmyoglobin than C VAC steaks. RC positively impacted bison steak tenderness and color in ground bison and steaks.


β-Lactoglobulin: An efficient nanocarrier for advanced delivery systems.
Thanks to the progress of nanotechnology there are several agent-delivery systems that can be selected to achieve rapid and specific delivery of a wide variety of biologically active agents. Consequently, the manipulation and engineering of biopolymers has become one of the most exciting subjects for those who study delivery systems on the nanoscale. In this regard, both nanoparticle formation and a carrier role have been observed in the case of the globular milk whey protein, β-lactoglobulin (β-LG), setting it apart from many other proteins. To date, many efforts adopting different approaches have created β-LG nanoparticles useful in forming delivery systems for various agents with specific targets. In this review, the potential of β-LG to play the role of an efficient and diverse carrier protein, as well as its ability to form a well-targeted nano-scale delivery system is discussed.


Electrophysiologic study of globus pallidus projections to the thalamic reticular nucleus.
This study was designed to explore the electrophysiological relationships between the globus pallidus (GP), the substantia nigra pars reticulata (SNr) and the thalamic reticular nucleus (TRN) in urethane-anesthetized rats. The neuronal activity of the rostral part of the TRN was recorded by microelectrodes. Single pulse electrical stimulation of the GP and SNr produced inhibition of the spontaneous activity of the majority of TRN neurons. Stimulation of the GP by microinjections of bicuculline (25 ng/300 nl) produced also inhibition of the spontaneous activity of the reticular neurons. This could lead to facilitation of the cerebral cortex, as the reticular nucleus is reciprocally connected to, and inhibits, the thalamic motor nuclei, that in turn excite the motor cortex.


Intestinal metaplasia in Barrett's oesophagus: An essential factor to predict the risk of dysplasia and cancer development.
To date, there is still uncertainty on the role of specialized intestinal metaplasia in the carcinogenic process of Barrett's oesophagus (BE); this fact seems of importance for planning adequate surveillance programs. To predict the risk of progression towards dysplasia/cancer based on typical morphological features by evaluating the importance of intestinal metaplasia in BE patients. 647 cases with a histological diagnosis of BE, referred to the Endoscopy Unit of a tertiary centre between 2000 and 2012 were retrospectively identified, and divided into two groups according to the presence/absence of intestinal metaplasia. For each patient, all histological reports performed during a follow-up of 4-8 years were analyzed. Overall, 537 cases (83%) with intestinal metaplasia and 110 cases (17%) without intestinal metaplasia were included. During the follow-up period, none of the patients without intestinal metaplasia developed dysplasia/cancer nor progressed to metaplasia, whereas 72 patients with intestinal metaplasia (13.4%) showed histological progression of the disease. The histological identification of intestinal metaplasia seems to be an essential factor for the progression towards dysplasia and cancer in BE patients.


Static and dynamic biomechanical properties of the regenerating rabbit Achilles tendon.
Since tendons show viscoelastic behavior, dynamic viscoelastic properties should be assessed in addition to static biomechanical properties. We evaluated differences between static and dynamic biomechanical properties of the regenerating rabbit Achilles tendon following tenotomy. At 3, 6, or 12 weeks after right Achilles tenotomy, the right (regenerating) and left (control) tendons were collected with the calcaneus from 49 rabbits. A unidirectional failure test and a dynamic viscoelastic test were conducted. Tensile strength and Young's modulus (static biomechanical properties) in the regenerating group at Week 6 were significantly greater than at Week 3, while at Week 12, these were significantly greater than at Week 6. However, even at Week 12, both parameters were less than in the control group. The value of tan delta represents dynamic viscoelasticity, a smaller tan delta indicates greater elasticity. tan delta for the regenerating group was significantly greater than for the control group at Week 3, but regenerating and control groups did not significantly differ at Week 6. No marked change was seen from Weeks 6 to 12 in the regenerating group, and no significant difference in tan delta was evident between the regenerating and control groups at Week 12. Dynamic biomechanical properties of regenerating rabbit Achilles tendons may improve more rapidly than static biomechanical properties. Ability to tolerate dynamic movement in the healing Achilles tendon may improve more rapidly than ability to withstand static stresses.


Performance of active learning models for screening prioritization in systematic reviews: a simulation study into the Average Time to Discover relevant records.
Conducting a systematic review demands a significant amount of effort in screening titles and abstracts. To accelerate this process, various tools that utilize active learning have been proposed. These tools allow the reviewer to interact with machine learning software to identify relevant publications as early as possible. The goal of this study is to gain a comprehensive understanding of active learning models for reducing the workload in systematic reviews through a simulation study. The simulation study mimics the process of a human reviewer screening records while interacting with an active learning model. Different active learning models were compared based on four classification techniques (naive Bayes, logistic regression, support vector machines, and random forest) and two feature extraction strategies (TF-IDF and doc2vec). The performance of the models was compared for six systematic review datasets from different research areas. The evaluation of the models was based on the Work Saved over Sampling (WSS) and recall. Additionally, this study introduces two new statistics, Time to Discovery (TD) and Average Time to Discovery (ATD). The models reduce the number of publications needed to screen by 91.7 to 63.9% while still finding 95% of all relevant records (WSS@95). Recall of the models was defined as the proportion of relevant records found after screening 10% of of all records and ranges from 53.6 to 99.8%. The ATD values range from 1.4% till 11.7%, which indicate the average proportion of labeling decisions the researcher needs to make to detect a relevant record. The ATD values display a similar ranking across the simulations as the recall and WSS values. Active learning models for screening prioritization demonstrate significant potential for reducing the workload in systematic reviews. The Naive Bayes + TF-IDF model yielded the best results overall. The Average Time to Discovery (ATD) measures performance of active learning models throughout the entire screening process without the need for an arbitrary cut-off point. This makes the ATD a promising metric for comparing the performance of different models across different datasets.


Prolonged perioperative thoracic epidural analgesia may improve survival after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A comparative study.
To assess the effectiveness of prolonged perioperative thoracic epidural analgesia (PEA) on long term survival of patients who underwent a complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM). Grade III-IV morbidity affects long term outcomes after CRS and HIPEC. As compared with opioid administered via patient-controlled analgesia (PCA), PEA reduces morbidity. From 2005 to 2016, 150 patients underwent CRS plus HIPEC with or without prolonged PEA. Clinical data and outcomes collected from prospective database were analyzed. Survival was assessed in terms of analgesic method using Kaplan-Meier plots and a propensity score. Patients 'characteristics of 59 patients in PCA group were comparable to those of 91 patients in PEA group, except for age, ASA score and fluid requirements, significantly more important in PEA group. Grade III-IV morbidity was 62.7% in PCA group compared with 36.3% in PEA group (p = 0.0015). Median overall survival (OS) of PEA group was 54.7 months compared to 39.5 months in PCA group (p = 0.0078). When adjusted on the covariates, using the propensity score, the PEA significantly improves OS [HR 0.40 (95% CI: 0.28-0.56)] (p < 0.0001) and disease free survival (DFS) [HR 0.61 (95% CI: 0.45-0.81] (p < 0.0007) CONCLUSIONS: In this retrospective study of patients who underwent a complete CRS and HIPEC for colorectal peritoneal metastases, the perioperative thoracic epidural analgesia prolonged for over 72 h reduced significantly the grade III-IV morbidity and may improve OS and DFS.


Esophageal adenocarcinoma with metastasis to the prostatic urethra and bladder.
Metastatic esophageal adenocarcinoma to the urinary bladder is extremely rare and aggressive. We discuss here the case of an 83-year-old male with history of esophageal adenocarcinoma treated with chemoradiation therapy and esophagectomy who presented with gross hematuria and lower urinary tract symptoms. Pathology of the bladder tumor after transurethral resection demonstrated invasive adenocarcinoma of both the bladder and the prostatic urethra consistent with metastatic esophageal adenocarcinoma.


Charge transfer in P-type ATPases investigated on planar membranes.
Planar lipid bilayers, e.g., black lipid membranes (BLM) and solid supported membranes (SSM), have been employed to investigate charge movements during the reaction cycle of P-type ATPases. The BLM/SSM method allows a direct measurement of the electrical currents generated by the cation transporter following chemical activation by a substrate concentration jump. The electrical current transients provides information about the reaction mechanism of the enzyme. In particular, the BLM/SSM technique allows identification of electrogenic steps which in turn may be used to localize ion translocation during the reaction cycle of the pump. In addition, using the high time resolution of the technique, especially when rapid activation via caged ATP is employed, rate constants of electrogenic and electroneutral steps can be determined. In the present review, we will discuss the main results obtained by the BLM and SSM methods and how they have contributed to unravel the transport mechanism of P-type ATPases.


Nanolayered tin phosphate: a remarkably selective Cs ion sieve for acidic waste solutions.
Herein, we report a unique tin phosphate that is remarkably selective to (137)Cs(+) from extremly acidic solutions because of its special layered structure with an unusually large interlayer space. This acidic exchanger is superior to other existing materials in terms of its selectivity and capacity for (137)Cs(+) from acidic solutions.


A carbon dioxide air-gap microelectrode based on a neutral hydrogen ion exchanger pH microelectrode.
A relatively simple potentiometric pCO2 gas-sensing microelectrode is described. It is based on an ion-exchanger pH electrode, has a 2- to 5-microns tip, and has an air gap which is formed by means of hydrophobic treatments. The microelectrode exhibits a linear response in the range 10(-4)-10(-2) M with a Nernstian slope of 59 to 62 mV/decade at 25 degrees C. Ninety-five percent of the steady-state response time is about 20-30 s at the flow system when the concentration of sodium bicarbonate in buffer solution (pH 4.5) suddenly shifts from 0.2 to 2 mM and the lifetime is longer than 1 week.


Orthotopic liver transplantation for hepatitis C infection: the best Christmas present?
We report the case of a 60-year-old man with mild Christmas disease, Factor IX 10% of normal, who developed chronic hepatitis C infection after receiving coagulation factor concentrates. Subsequently he developed encephalopathy and liver failure and was referred for liver transplantation. Following transplantation, Factor IX levels rapidly normalised and have remained so, representing a phenotypic cure of his Christmas disease.


High prevalence of inducible clindamycin resistance among Staphylococcus aureus isolates from patients with cystic fibrosis.
Staphylococcus aureus (SA) is an important pathogen among patients with cystic fibrosis (CF). Inducible clindamycin resistance (ICR) has been described as a cause of treatment failure in non-CF related infections. The prevalence of ICR among SA from patients with CF is unknown. We compared clindamycin susceptibilities of SA isolated from patients with and without cystic fibrosis (CF) using hospital microbiology data. Patients with CF were primarily identified using CF registry data. We evaluated all patients who had SA isolated at the Children's Healthcare of Atlanta microbiology laboratory during May 2004-May 2005. We performed antimicrobial susceptibility testing using broth microdilution and performed D-zone testing for ICR in accordance with the Clinical Laboratory Standards Institute (CLSI) document M100-S16. Proportions were compared using a 2-sided Pearson's Chi-square test or Fisher's exact test to assess for significance. Of 703 patients with methicillin-resistant SA (MRSA), 48% of CF patients (68/143) had at least one isolate demonstrating ICR, compared to 8% of non-CF patients (43/560) (P<0.01). Of 762 patients with methicillin-susceptible SA (MSSA), 29% of CF patients (73/254) had at least one isolate demonstrating ICR compared to 17% of non-CF patients (88/508) (P<0.01). SA demonstrating ICR are significantly more prevalent among patients with CF than among those without CF.


Regional differences in veins wall viscosity, compliance, energetics and damping: analysis of the pressure-diameter relationship during cyclical overloads.
The characterization of the dynamic process of veins walls is essential to understand venous functioning under normal and pathological conditions. However, little work has been done on dynamic venous properties. To characterize vein compliance (C), viscosity (eta), peak-strain (W St) and dissipated (W(D)) energy, damping (zeta), and their regional differences in order to evaluate their role in venous functioning during volume-pressure overloads. In a mock circulation, pressure (P) and diameter (D) of different veins (anterior cava, jugular and femoral; from 7 sheep), were registered during cyclical volume-pressure pulses. From the P-D relationship, C, W(St) and zeta (at low and high P-D levels), eta and W(D) were calculated. For each vein there were P-dependent differences in biomechanical, energetics, and damping capability. There were regional-differences in C, eta), W(St) and W(D) (p<0.05), but not in zeta. The regional-dependent differences in dynamics and energetics, and regional-similitude in damping could be important to ensure venous functioning during acute overloads. The lower C and higher W(St) and W(D) found in back-limb veins (femoral), commonly submitted to high volume-pressure loads (i.e. during walking), could be considered relevant to ensure adequate venous system functionality and venous wall protection simultaneously.


Chromosomal localization of the human interleukin 1 alpha (IL-1 alpha) gene.
The human interleukin 1 alpha gene was assigned to chromosome 2 using Southern transfer analysis of human-rodent somatic cell hybrid DNAs. The gene was regionally localized to 2q12-21 using in situ hybridization to metaphase chromosomes. These results indicate that the IL-1 alpha gene maps to the same general region on the long arm of chromosome 2 as the IL-1 beta gene, which has been previously assigned.


Donor and recipient origin of herpesvirus-reactive lymphocytes after bone marrow transplantation. Brief report.
Cellular reactivity to herpesviruses was studied after bone marrow transplantation (BMT). In 3 patients all virus-stimulated lymphocytes were of donor type. In the fourth patient, 14 per cent of the HSV stimulated cells were of recipient origin at 6 months after BMT.


A new allele for aluminium tolerance gene in barley (Hordeum vulgare L.).
Aluminium (Al) toxicity is the main factor limiting the crop production in acid soils and barley (Hordeum vulgare L.) is one of the most Al-sensitive of the small-grained cereals. The major gene for Al tolerance in barley is HvAACT1 (HvMATE) on chromosome 4H which encodes a multidrug and toxic compound extrusion (MATE) protein. The HvAACT1 protein facilitates the Al-activated release of citrate from root apices which protects the growing cells and enables root elongation to continue. A 1 kb transposable element-like insert in the 5' untranslated region (UTR) of HvAACT1 is associated with increased gene expression and tolerance and a PCR-based marker is available to score for this insertion. We screened a wide range of barley genotypes for Al tolerance and identified a moderately tolerant Chinese genotype named CXHKSL which did not show the typical allele in the 5' UTR of HvAACT1 associated with tolerance. We investigated the mechanism of Al tolerance in CXHKSL and concluded it also relies on the Al-activated release of citrate from roots. Quantitative trait loci (QTL) analysis of double haploid lines generated with CXHKSL and the Al-sensitive variety Gairdner mapped the tolerance locus to the same region as HvAACT1 on chromosome 4H. Our results show that the Chinese barley genotype CXHKSL possesses a novel allele of the major Al tolerance gene HvAACT1.


Population Pharmacokinetic Evaluation with External Validation of Tacrolimus in Chinese Primary Nephrotic Syndrome Patients.
The generalizability of numerous tacrolimus population pharmacokinetic (popPK) models constructed to promote optimal tacrolimus dosing in patients with primary nephrotic syndrome (PNS) is unclear. This study aimed to evaluate the predictive performance of published tacrolimus popPK models for PNS patients with an external data set. We prospectively collected 223 concentrations from 50 Chinese adult patients with PNS who were undergoing tacrolimus treatment. Data on published tacrolimus popPK models for adults and children with PNS were extracted from the literature. Model predictability was evaluated with prediction-based and simulation-based diagnostics and Bayesian forecasting. In prediction-based evaluation, none of the 11 identified published popPK models of tacrolimus had met a predefined criteria of a mean prediction error ≤ ± 20%, and the prediction error within ± 30% of the identified models didn't exceed 50%. Simulation-based diagnostics also indicated unsatisfactory predictability. Bayesian forecasting demonstrated amelioration in the model predictability with the inclusion of 2-3 prior observations. Moreover, the predictive performance of nonlinear models was not better than that of one-compartment models. The prediction of tacrolimus concentrations for patients with PNS remains challenging; published models are not applicable for extrapolation to other hospitals. Bayesian forecasting significantly improved model predictability and thereby helped to individualize tacrolimus dosing.


ECoG spiking activity and signal dimension are early predictive measures of epileptogenesis in a translational mouse model of traumatic brain injury.
The latency between traumatic brain injury (TBI) and the onset of epilepsy (PTE) represents an opportunity for counteracting epileptogenesis. Antiepileptogenesis trials are hampered by the lack of sensitive biomarkers that allow to enrich patient's population at-risk for PTE. We aimed to assess whether specific ECoG signals predict PTE in a clinically relevant mouse model with ∼60% epilepsy incidence. TBI was provoked in adult CD1 male mice by controlled cortical impact on the left parieto-temporal cortex, then mice were implanted with two perilesional cortical screw electrodes and two similar electrodes in the hemisphere contralateral to the lesion site. Acute seizures and spikes/sharp waves were ECoG-recorded during 1 week post-TBI. These early ECoG events were analyzed according to PTE incidence as assessed by measuring spontaneous recurrent seizures (SRS) at 5 months post-TBI. We found that incidence, number and duration of acute seizures during 3 days post-TBI were similar in PTE mice and mice not developing epilepsy (No SRS mice). Control mice with cortical electrodes (naïve, n = 5) or with electrodes and craniotomy (sham, n = 5) exhibited acute seizures but did not develop epilepsy. The daily number of spikes/sharp waves at the perilesional electrodes was increased similarly in PTE (n = 15) and No SRS (n = 8) mice vs controls (p < 0.05, n = 10) from day 2 post-injury. Differently, the daily number of spikes/sharp waves at both contralateral electrodes showed a progressive increase in PTE mice vs No SRS and control mice. In particular, spikes number was higher in PTE vs No SRS mice (p < 0.05) at 6 and 7 days post-TBI, and this measure predicted epilepsy development with high accuracy (AUC = 0.77, p = 0.03; CI 0.5830-0.9670). The cut-off value was validated in an independent cohort of TBI mice (n = 12). The daily spike number at the contralateral electrodes showed a circadian distribution in PTE mice which was not observed in No SRS mice. Analysis of non-linear dynamics at each electrode site showed changes in dimensionality during 4 days post-TBI. This measure yielded the best discrimination between PTE and No SRS mice (p < 0.01) at the cortical electrodes contralateral to injury. Data show that epileptiform activity contralateral to the lesion site has the the highest predictive value for PTE in this model reinforcing the hypothesis that the hemisphere contralateral to the lesion core may drive epileptogenic networks after TBI.


Glutathione peroxidase, thioredoxin, and membrane protein changes in erythrocytes predict ribavirin-induced anemia.
Low erythrocyte membrane protein sulfhydril concentrations are a risk factor for ribavirin-induced anemia. We further studied the role of oxidative stress and erythrocyte membrane alterations in ribavirin-induced anemia. The levels of thioredoxin, glutathione peroxidase, protein sulfhydrils, and protein-mixed disulfides, as well as the electrophoretic membrane protein pattern, were determined in freshly isolated erythrocytes from healthy control subjects, patients without severe anemia during previous ribavirin treatment (still hepatitis C virus [HCV]-positive), and patients who had had severe anemia with ribavirin (still HCV-positive or HCV-negative), 6 months after full recovery. Erythrocytes were also incubated with buffer, ribavirin, phenylhydrazine, or dehydroepiandrosterone, and concentrations of protein sulfhydrils, protein-mixed disulfides, thiobarbituric acid-reactive substances, and total and oxidized glutathione, as well as osmotic resistance, were determined. Patients with previous severe ribavirin-induced anemia had lower levels of protein sulfhydrils (30.9 nmol/mg protein versus 43.2 nmol/mg protein, P<.001) and thioredoxin (0.6 nmol/g hemoglobin versus 1.2 nmol/g hemoglobin, P<.001), higher levels of protein-mixed disulfides (1.5 nmol/g hemoglobin versus 0.5 nmol/g hemoglobin, P<.001) and glutathione peroxidase (618 mU/mg protein versus 393 mU/mg protein, P<.001), and a membrane protein pattern consistent with band 4 dimer disaggregation. These differences were independent of HCV seropositivity. There were negative correlations between levels of glutathione peroxidase and thioredoxin (r=-0.87) and between levels of protein sulfhydrils and protein-mixed disulfides (r=-0.93). In vitro studies showed that erythrocytes of patients who had had hemolysis during treatment of HCV are more susceptible to oxidative stress. Pronounced differences in markers of oxidative stress and membrane proteins exist between patients with and without a history of ribavirin-induced anemia. Our findings suggest that there are erythrocyte-related risk factors for ribavirin-induced severe anemia.


Development of a toxin-binding agent as a treatment for tunicaminyluracil toxicity: protection against tunicamycin poisoning of sheep.
To assess the ability of certain derivatives of beta-cyclodextrin to treat sheep affected by tunicaminyluracil toxicity, using tunicamycin poisoning as a model system. Controlled treatment trial. One hundred and sixty Merino wethers were used in the studies. Groups of sheep were experimentally poisoned with tunicamycin. Derivatives of beta-cyclodextrin, with or without magnesium sulphate and magnesium gluconate, were administered to treatment groups daily for 2 to 3 days. Treatment groups were compared with untreated groups in terms of survival. A significant increase in survival was observed following treatment of tunicamycin-affected sheep with hydroxypropyl-beta-cyclodextrin (HP beta-CD) and magnesium sulphate in solution (P < 0.05). In subsequent trials, formulation of the cyclodextrin in the form of a magnesium gluconate gel suspension demonstrated significant protection (P < 0.01) and was equally as effective as the cyclodextrin in solution, but required half the frequency of administration, even when the treatment was not commenced until 24 h after the final toxin dose. Beta-cyclodextrin-epichlorohydrin copolymer also improved the survival rate. After toxin administration, the sheep lost significantly less weight if treatment with HP beta-CD was commenced early (P < 0.001). Protection studies using these two beta-cyclodextrin derivatives suggest that they may be effective in increasing the survival of sheep poisoned by tunicamycin and warrant further testing in field outbreaks of annual ryegrass toxicity.


Characterization of two molecules at 30,33 kDa as major target antigens of natural thymocytotoxic autoantibodies.
We have attempted to characterize, by immunoblotting, the cell surface determinants which are recognized by natural thymocytotoxic autoantibodies (NTA). NTA-positive sera from spontaneously autoimmune mice and from mice rendered autoreactive by neonatal induction of tolerance were used as probes on blots of thymocytes. Fifty percent of the sera screened under these conditions reacted with a doublet of 30,33 kDa molecular weight present on membranes, but not detectable on blots of total cell extracts. Additional bands of various molecular weights were detected by NTA-positive sera at a much lower frequency than the 30,33 kDa determinants. Direct evidence of identity between the antibodies inducing thymocytotoxicity and those detecting the doublet in immunoblotting was provided by immunoadsorption tests. Among a panel of immunoadsorbents prepared with thymocyte membrane proteins of various molecular weights, only the one containing the 30,33 kDa molecules efficiently adsorbed cytotoxic antibodies whereas the other preparations containing some of the bands occasionally detected in immunoblotting had practically no effect. In addition we showed that the 30,33 kDa doublet is also detected on membrane preparations of T and B lymphocytes but not on preparations of a nonlymphoid cell line, and is composed of two independent molecules not covalently linked, in their native configuration, by disulfide bonds. Altogether these results strongly suggest that the 30,33 kDa molecules represent major cell surface determinants for thymocytotoxic autoantibodies.


The Computerized ECG: Friend and Foe.
Computerized interpretation of the electrocardiogram (ECG) began in the 1950s when conversion of its analog signal to digital form became available. Since then, automatic computer interpretations of the ECG have become routine, even at the point of care, by the addition of interpretive algorithms to portable ECG carts. Now, more than 100 million computerized ECG interpretations are recorded yearly in the United States. These interpretations have contributed to medical care by reducing physician reading time and accurately interpreting most normal ECGs. But errors do occur. The computer cannot be held responsible for misinterpretations due to recording errors, such as muscle artifacts or lead reversal. But, in many abnormal ECGs, the computer makes its own errors-sometimes critical-in its incorrect detection of arrhythmias, pacemakers, and myocardial infarctions. These errors require that all computerized statements be over-read by trained physicians who have the advantage of clinical context, unavailable to the computer. Together, the computer and over-readers now provide the most accurate ECG interpretations available.


PP2A methylation controls sensitivity and resistance to β-amyloid-induced cognitive and electrophysiological impairments.
Elevated levels of the β-amyloid peptide (Aβ) are thought to contribute to cognitive and behavioral impairments observed in Alzheimer's disease (AD). Protein phosphatase 2A (PP2A) participates in multiple molecular pathways implicated in AD, and its expression and activity are reduced in postmortem brains of AD patients. PP2A is regulated by protein methylation, and impaired PP2A methylation is thought to contribute to increased AD risk in hyperhomocysteinemic individuals. To examine further the link between PP2A and AD, we generated transgenic mice that overexpress the PP2A methylesterase, protein phosphatase methylesterase-1 (PME-1), or the PP2A methyltransferase, leucine carboxyl methyltransferase-1 (LCMT-1), and examined the sensitivity of these animals to behavioral and electrophysiological impairments caused by exogenous Aβ exposure. We found that PME-1 overexpression enhanced these impairments, whereas LCMT-1 overexpression protected against Aβ-induced impairments. Neither transgene affected Aβ production or the electrophysiological response to low concentrations of Aβ, suggesting that these manipulations selectively affect the pathological response to elevated Aβ levels. Together these data identify a molecular mechanism linking PP2A to the development of AD-related cognitive impairments that might be therapeutically exploited to target selectively the pathological effects caused by elevated Aβ levels in AD patients.


Plantibodies: applications, advantages and bottlenecks.
Various strategies have been developed to exploit plants as bioreactors for the production of pharmaceutical antibodies, to engineer antibody-mediated pathogen resistance or to alter the plant phenotype by immunomodulation. Recent research developments focus on the fine-tuning of expression systems and the detailed characterisation of recombinant products, including the implications of plant-specific glycosylation. Meanwhile, the first of these plant-derived antibody products has successfully completed early phase clinical trials.


Impact of atypical antipsychotics on outcomes of care in schizophrenia.
To compare persistence, compliance, and psychiatric treatment costs in patients who were initiated on atypical antipsychotics. Medical and pharmacy claims data were used to compare persistence (days of therapy between first and last prescriptions, allowing therapy gaps < 90 days); compliance (ratio of days of medication supplied to total days on therapy); treatment costs in adults with schizophrenia having claims for atypical antipsychotics from March 2001 to August 2003; and enrollment for > or =6 months before and > or =12 months after therapy initiation. Psychiatric treatment costs for 1 year were examined before and after therapy initiation. Differences in costs were tested by univariate analyses. Persistence was approximately 30 days longer for patients receiving ziprasidone (n = 217; 228 days) than risperidone (n = 831; 193 days) or olanzapine (n = 762; 201 days). Compliance was significantly (P<.05) higher among patients receiving ziprasidone (87%) compared with other treatments (78%-80%). Ziprasidone patients had significantly larger decreases (- USD 6866) in mean annual psychiatric-related costs following therapy initiation than those on risperidone (- USD 3353; P = .0116) or olanzapine (- USD 4764; P = .0021). The primary driver of cost savings was reduced hospitalization after treatment initiation. Patients initiated on ziprasidone had longer persistence, better compliance, and greater decreases in psychiatric-related costs than those initiated on other atypicals.


A review on urban agriculture: technology, socio-economy, and policy.
It has been a challenge to support the expansion of urban agriculture (UA) in cities due to its poor economic profitability. However, it is also hard to deny the increasing benefits of UA in improving the socio-environmental dimension of cities. Hence, in this review, different aspects of UA were examined to highlight its value beyond profitability such as social, health and well-being, disaster risk reduction, and environmental perspectives. A case study and relevant policies were analyzed to determine how policy makers can bridge the gap between current and future UA practices and sustainable development. Bridging these policy gaps can help the UA sector to sustainably grow and become successfully integrated in cities. Moreover, advancements in UA technologies and plant biotechnology were presented as potential solutions in increasing the future profitability of commercial UA. Consequently, as new UA-related technologies evolve, the multidisciplinary nature of UA and its changing identity from agriculture to digital technology, similarly require adaptive policies. These policies should maximize the potential of UA in contributing to resiliency and sustainability and incentivize the organic integration of UA in cities, while equally serving social justice.


Chronic post-operative opioid use after open cardiac surgery: A Danish population-based cohort study.
Knowledge of chronic opioid use after cardiac surgery is sparse. We therefore aimed to describe the proportion of new chronic post-operative opioid use after open cardiac surgery. We used prospectively registered data from a national prescription registry and a clinical registry of 29 815 first-time cardiac surgeries from three Danish university hospitals. Data collection spanned from 2003 to 2016. The main outcome was chronic post-operative opioid use, defined as at least one opioid dispensing in the fourth post-operative quarter. Data were assessed for patient-level predictors of chronic post-operative opioid use, including pre-operative opioid use, opioid use at discharge, comorbidities, and procedural related variables. The overall proportion of post-operative opioid use was 10.6% (95% CI: 10.2-10.9). The proportion of new chronic post-operative opioid use was 5.7% (95% CI: 5.5-6.0) among pre-operative opioid naïve patients. The corresponding proportions among patients, who pre-operatively used low or high dose opioid (1-500 mg or > 500 mg cumulative morphine equivalent opioid), were 68.3% (95% CI: 66.1-70.4) and 76.3% (95% CI: 74.0-78.5) respectively. Risk factors associated with new chronic post-operative opioid use included: female gender, underweight and obesity, pre-operative comorbidities, acute surgery, ICU-time > 1 day, and post-operative complications. Strongest predictor of chronic post-operative opioid use was post-discharge use of opioid within one month after surgery (odds ratio 3.3, 95% CI: 2.8-4.0). New chronic post-operative opioid use after open cardiac surgery is common. Focus on post-discharge opioid use may help clinicians to reduce rates of new chronic opioid users.


Effect of ascovertin on morphofunctional changes in the ovaries in monopolar coagulation.
A course of ascovertin therapy reduced manifestations of perifocal inflammation and atresia of growing follicles, corrected vascular disorders and changes in the tissue volume ratios outside the necrotic zone after monopolar coagulation of the ovaries in rats. The drug prevented the increase in blood viscosity, erythrocyte aggregation, and LPO activation in the early postoperation period.


[Stanisław Kopczyński, a specialist in internal medicine and neurology--pioneer of school sanitary sciences in Poland].
The beginnings of school hygiene are connected with the work of dr Stanisław Kopczyński (1873-1933), specilist in internal medicine and neurologist, who after the First World War organised hygenic and medical care in schools all over the country.


Covert preleukemia driven by MLL gene fusion.
Acute leukemia is considered to be a two- or multiple-step process. Although there is a considerable knowledge regarding the character of the "first hit," the nature of the "second hit" remains unanswered in most of the cases including leukemias with MLL gene rearrangement. We demonstrate here a striking sequence of events, which include a covert, protracted preleukemic phase characterized by a dominant MLL/FOXO3A clone with intact myeloid differentiation and the subsequent acquisition of a secondary genetic abnormality, leading to overt lymphoblastic leukemia. Backtracking of the secondary acute lymphoblastic leukemia (sALL) with the MLL rearrangement showed no blasts in the bone marrow (BM) during the protracted preleukemic phase. However, at the same time (more than 1 year before the sALL diagnosis) the MLL/FOXO3A was present in up to 90% of BM cells including myeloid lineage, suggesting that the fusion arose in a multipotent progenitor. To identify potential "second hit" precipitating sALL we compared DNA in preleukemic versus fully leukemic samples. The analysis revealed a 10 Mb gain on 19q13.32 in the sALL, absent in the preleukemic specimen. These data provide insight into the dynamics of leukemogenesis in secondary leukemia with MLL rearrangement.


3-Methylcrotonylglycine excretion in 3-hydroxy-3-methylglutaric aciduria.
1. 3-Methylcrotonylglycine was identified in urine from an infant with 3-hydroxy-3-methylglutaric aciduria. 2. The concentration of 3-methylcrotonylglycine in urine was approximately one sixth of that of the other metabolite of 3-methylcrotonyl-CoA, 3-hydroxyisovaleric acid. 3. The presence of both metabolites in the infant's urine indicates an inhibition of 3-methylcrotonyl-CoA carboxylase activity in tissues of the infant.


Constructing porous carbon nitride nanosheets for efficient visible-light-responsive photocatalytic hydrogen evolution.
The photocatalytic performance of polymeric carbon nitride (CN) is mainly restricted by the poor mass charge separation efficiency and poor light absorption due to its polymeric nature. The conventional strategies to address these problems involved constructing a nanosheets structure would result in a blue shifted light absorption and increased exciton binding energy. Here, with combination of ammonia etching and selectively hydrogen-bond breaking, holey carbon nitride nanosheets (hCNNS) were constructed, thus widening the light absorption range, and spontaneously shortening the migration distance of electrons and holes in the lateral and vertical directions, respectively. Further analysis also found out the reserved atomic structure order endowed hCNNS with the relatively high redox potential. When irradiated with visible light (λ > 420 nm) and loaded with 3 wt% Pt as the cocatalyst, the hydrogen evolution rate of hCNNS was about 40 times higher than the bulk CN, and the apparent quantum yield (AQY) of hCNNS is 1.47% at 435 ± 15 nm. We expect this research can provide a new sight for achieving highly efficient solar utilization of CN-based photocatalysts.


Pharmacokinetics of intravenous immunoglobulin in neonates.
Intravenous immunoglobulin (IVIG) may be a therapeutic adjunct to antibiotic treatment of neonatal infections. We examined the pharmacokinetics and safety of IVIG in human neonates. Thirty neonates with suspected sepsis were randomly assigned either to a treatment (receiving either 250, 500, or 1,000 mg/kg of IVIG plus antibiotics) or control (antibiotics alone) group. The 500 mg/kg dose produced a rise in total IgG for greater than 8 and in group B streptococcus (GBS) type-specific IgG for greater than 4-14 days. The type-specific antibody elevation varied with the amount of pathogen-specific antibody and dose of IVIG. Pharmacokinetic analysis suggests a Vdss of 42 ml/kg, Cl of 3.0 ml/kg/day, a biphasic elimination curve, and a terminal elimination half-life of 24.2 days. No toxicity was observed. These data may be valuable in determining optimal dosing schedules for IVIG in treating or preventing neonatal infections.


Molecular characterization of methionine aminopeptidase1 from Eimeria tenella.
Coccidiosis, a serious intestinal parasitic disease caused by Eimeria spp., can result in huge annual economic losses to the poultry industry worldwide. At present, coccidiosis is mainly controlled by anticoccidial drugs. However, drug resistance has developed in Eimeria because of the long-term and unreasonable use of the drugs currently available. In our previous study, RNA-seq showed that the expression of methionine aminopeptidase1 (EtMetAP1) was up-regulated in diclazuril-resistant (DZR) and maduramicin-resistant (MRR) strains compared to drug-sensitive (DS) strain of Eimeria tenella. In this study, EtMetAP1 was cloned and expressed, and the function and characteristics of the EtMetAP1 protein were analyzed. The transcription and translation levels of EtMetAP1 in DS strain of E. tenella at different developmental stages were analyzed by qPCR and western blotting. We found that the transcription and translation levels of EtMetAP1 in second-generation merozoites (SM) were higher than those of the other three stages (unsporulated oocyst, sporulated oocyst, and sporozoites). Simultaneously, qPCR was used to analyze the mRNA transcription levels of EtMetAP1 in DS, DZR, MRR, and salinomycin-resistant (SMR) strain. The results showed that compared to the sensitive strain, the transcription levels of EtMetAP1 in DZR and MRR were up-regulated. There was no significant difference in transcription level in SMR. Indirect immunofluorescence localization showed that the protein was mainly localised in the cell membrane and cytoplasm of sporozoites and SM. An invasion inhibition test showed that anti-rEtMetAP1 polyclonal antibody could effectively inhibit the sporozoite invasion of host cells. These results suggest that the protein may be involved in the growth and development of parasites in host cells, the generation of drug resistance, and host cell invasion.


Microbial production of valuable chemicals by modular co-culture strategy.
Nowadays, microbial synthesis has become a common way for producing valuable chemicals. Traditionally, microbial production of valuable chemicals is accomplished by a single strain. For the purpose of increasing the production titer and yield of a recombinant strain, complicated pathways and regulation layers should be fine-tuned, which also brings a heavy metabolic burden to the host. In addition, utilization of various complex and mixed substrates further interferes with the normal growth of the host strain and increases the complexity of strain engineering. As a result, modular co-culture technology, which aims to divide a target complex pathway into separate modules located at different single strains, poses an alternative solution for microbial production. Recently, modular co-culture strategy has been employed for the synthesis of different natural products. Therefore, in this review, various chemicals produced with application of co-cultivation technology are summarized, including co-culture with same species or different species, and regulation of population composition between the co-culture members. In addition, development prospects and challenges of this promising field are also addressed, and possible solution for these issues were also provided.