Long-term effectiveness of the preoperative smoking cessation programme at Western Health.
Smoking is associated with adverse effects in the perioperative period, including elevated risk of death. The perioperative period provides an opportunity to engage with patients who are smokers to encourage smoking cessation, often referred to as a 'teachable moment'. We developed a smoking intervention model for the pre-admission clinic (PAC) at Western Health, Victoria, Australia. This case series aimed to assess the impact of the smoking intervention model, which is standard of care, on the participant's smoking habits over four time points. We enrolled 50 consecutive participants for elective surgery who were smokers and had attended PAC at Western Health, Footscray. All smokers were offered a standard intervention package to address their smoking. Participants underwent a brief interview to elicit their current smoking behaviour on their day of surgery, 3 and 12 months post-operatively. We found a reduction at each time point post-intervention in the average number of cigarettes smoked per day by all participants with a 43% reduction at 12 months compared with PAC. We found that the number of participants who had quit increased at each time point, with 29% abstinent at 12 months post-operatively. At 12 months, we found 71% of participants had either quit or reduced the number of cigarettes smoked compared with the amount reported at PAC. This study adds to the evidence that a simple intervention preoperatively can contribute to long-term changes in smoking behaviour.


Optimization Strategy of College Students' Education Management Based on Smart Cloud Platform Teaching.
With the passage of time and social changes, the form of education is also changing step by step. In just a few decades, information technology has developed by leaps and bounds, and digital education has not yet been widely promoted. Intelligent education cloud platforms based on big data, Internet of things, cloud computing, and artificial intelligence have begun to emerge. The research on the "smart campus" cloud platform is conducive to improving the utilization rate of existing hardware equipment in colleges and universities and is conducive in improving the level of teaching software deployment. At the same time, this research also provides a new idea for the research in the field of cloud security. While cloud computing brings convenience to teaching work, it also brings new problems to system security. At present, virtualization technology is still in the ascendant stage in the construction of "smart campus" in colleges and universities and is gradually applied to cloud computing service products. At present, there are many cases about the construction of teaching resource platform, but most of them are modified from the early resource management system, which has strong coupling of single system, insufficient functions of collecting, processing, searching, sharing, and reusing resources, and weak application support ability for related business systems. Under this social background, this paper studies the teaching process management system for intelligent classroom.


Hepatic and adrenal hemangioendothelioma-a case report.
Haemangioendothelioma (HE) liver is a mesenchymal vascular tumour, intermediate between a haemangioma and an angiosarcoma. It has a variable clinical course, is a low grade malignancy and is associated with long-term survival. It has a characteristic histologic appearance. Immunohistochemical studies have shown that the neoplastic cells in HE are of endothelial derivation. These are essential to distinguish HE from metastatic carcinoma and primary epithelial liver tumour. We report a case of a 36-year-old male with HE of the liver with adrenal involvement, probably metastatic, with tuberculosis as an incidental finding. To our knowledge this is the first such case reported in literature. The confirmation of diagnosis was done by immunohistochemical study.


Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D.
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for "IBS mimickers" such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism.


Macroscopic small bowel mucosal injury caused by chronic nonsteroidal anti-inflammatory drugs (NSAID) use as assessed by capsule endoscopy.
To evaluate the type, frequency, and severity of macroscopic small bowel mucosal injury after chronic NSAID intake as assessed by capsule endoscopy (CE), as well as to correlate the severity of gastroduodenal and intestinal damage in these patients. A prospective, endoscopist-blind, controlled trial. Sixteen patients (14F/2M; age: 57.06 +/- 10.16 yrs) with osteoarthritis (OA) on chronic therapy with NSAIDs underwent CE and upper gastrointestinal endoscopy (UGE). Seventeen patients with OA (9F/2M; age: 57.47 +/- 9.82 yrs) who did not take NSAIDs were included as a control group. A scale ranging from 0 to 2 (0 = no lesions, 1-minor = red spots or petechiae, denuded areas and/or 1-5 mucosal breaks; 2-major = > 5 mucosal breaks and/or strictures, or hemorrhage) was designed to assess the severity of small bowel mucosal injuries. CE found intestinal lesions in 75% (12/16) of patients in the study group and in 11.76% (2/17) of controls (p < 0.01). Seven out of 16 NSAID consumers (43.75%) and none in the control group (0%) had a major small bowel mucosal injury (p < 0.01). The percentages of patients with grade 1 and 2 gastroduodenopathy in the study group, as assessed by UGE, were 37.14 and 23.81%, respectively. There was no significant difference in the rate of major enteropathy between patients with none or minor gastroduodenal injury, and those with major gastroduodenopathy (43.75 vs. 40%; p = N.S.). Chronic NSAID intake is associated with a high rate of small bowel mucosal injuries. Our data have failed to demonstrate a relationship between the severity of gastroduodenal and intestinal injury.


Refractory period after exercise-induced asthma unexplained by respiratory heat loss.
Fifteen asthmatic children and young adults each exercised for 6 min by cycling on a cycle ergometer while breathing either cold (4.1 degrees C +/- 0.5 SEM) and dry (2.05 mg/L +/- 0.05) air or warm (37.2 degrees C +/- 0.3) fully saturated air. Each subject performed 4 tests arranged in pairs. Test pair A consisted of cold dry exercise followed by another cold dry exercise and test pair B consisted of a warm humid exercise followed by a cold dry exercise. Ventilation, heart rate, and gas exchange were closely matched in all 4 tests in each subject with a mean oxygen consumption of 34.8 +/- 0.8 ml/min/kg. In test pair A, all subjects were rendered refractory by the first cold dry exercise as manifested by a significant attenuation of their exercise-induced asthma (EIA) after the second cold dry test (per cent decrease in FEV1, delta FEV1 = 16 +/- 4 compared with 38 +/- 4). In 3 subjects, the warm humid exercise did not cause EIA and did not render them refractory to the second cold dry exercise. The 12 remaining subjects exhibited a refractory period similar to that shown in test pair A. They did not develop EIA after the warm humid test (delta FEV1 = 1 +/- 2), but after the subsequent cold dry exercise the per cent decrease in FEV1 was 19 +/- 3, similar to that in the second of the 2 cold dry exercise tests. These experiments suggest that in the majority of subjects exercise per se appears to be the cause for refractoriness and not airway cooling or bronchoconstriction.


Washout and delayed start designs for identifying disease modifying effects in slowly progressive diseases using disease progression analysis.
Treatment of a slowly progressive disease, such as Parkinson's and Alzheimer's disease should slow down or even reverse progression of the disease. For estimating the actual treatment effect a clinical trial should allow the time course of treatment effects to be distinguished from those due to natural disease progression. A symptomatic treatment effect has a rapid onset, which will disappear after treatment cessation, whereas disease modifying effects are slow and persistent. Our objective was to compare the power of washout and delayed start designs for distinguishing symptomatic and disease modifying effects using disease progression modelling. The effect of dropout due to worsening disease status on the power was also considered.The change in the Unified Parkinson's Disease Rating Scale score over time was simulated, assuming that a treatment has a combined symptomatic and disease modifying effect. The simulated data were then fitted with the combined effect model and also with alternative models with either symptomatic or disease modifying effects alone. The power was derived from the number of times that the true model was correctly distinguished from the alternative models.Including a washout period in which the subjects are followed up after cessation of treatment substantially increases the power to distinguish different treatment effect types (washout>80%; delayed start<60%). Dropout of 40%-50% during the trial has a small effect on power (7% decrease). Under the assumptions of the simulation we found a clear advantage from using the washout design compared with a delayed start design.


Cytotoxic and genotoxic effects of an endemic plant of Turkey Salvia kronenburgii on breast cancer cell lines.
The natural products derived from plants are the important sources that can be used for breast cancer treatment. Salvia species and their derived products were recommended as potential antitumor substances. The potential cytotoxic and genotoxic effects of Salvia kronenburgii have been investigated on breast cancer cell lines, MCF-7 and MDA-MB-231. Determination of chemical compounds of S. kronenburgii was done using a gas chromatography coupled to time-of-flight mass spectrometry system and a dual-stage commercial thermal desorption injector. Growth inhibition of the S. kronenburgii was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and ATP viability assays. The cell death mode was detected by fluorescent dyes. Genotoxic effect of S. kronenburgii was measured by comet assay. S. kronenburgii showed antiproliferative effect in a dose-dependent manner on MCF-7 and MDA-MB-231 cell lines by inducing apoptosis-like cell death. The pyknotic cell nuclei were observed at the cell lines in response to S. kronenburgii. Furthermore, significant increase was shown in genetic damage index and frequencies in the damaged cells. S. kronenburgii might be a promising natural source for cancer therapy. Further experiments need to be done in vivo to understand of the anticancer effects of this plant.


[Sequelae secondary to heat-related illness].
Some patients with heatstroke suffer neurological sequelae. The incidence was 2.2 % in patients with heat-related illness in an analysis of the medical data from the Heatstroke STUDY 2006, the Heatstroke STUDY 2008 and the Heatstroke STUDY 2010, which were carried out by the Heatstroke Surveillance Committee of the Japanese Association for Acute Medicine (JAAM). Heatstroke patients who arrived at the hospital presenting with severe disturbance of consciousness, a higher body temperature or low BE values were more likely to experience central nervous system sequelae, and they were treated for a longer cooling time to achieve the target temperature. It is therefore important to provide aggressive cooling and intensive care as rapidly as possible in order to avoid the occurrence of the neurological sequelae of heatstroke.


The preoperative management of phaeochromocytoma.
Although the preoperative use of alpha-receptor antagonist drugs is generally accepted for patients with phaeochromocytoma, evidence on the most appropriate treatment and its timing is scarce. In this retrospective study, the effectiveness of the preoperative preparation of fourteen patients who required surgical excision of a phaeochromocytoma was examined in the light of their operative stability. A simple score was developed of blood pressure stability by scoring the need for additional antihypertensive agents intraoperatively before, and blood pressure support after, tumour removal. A higher score indicated greater instability. Twelve patients received phenoxybenzamine and their stability was superior to the two patients treated with labetalol and with prazosin. There was no correlation between the duration of treatment with phenoxybenzamine and the operative stability (r = 0.18 P = 0.55 Spearman). The five patients who were treated with phenoxybenzamine for longer than 10 days did not have better perioperative blood pressure stability than the five patients who had treatment for less than a week. Predictive factors for intra-operative blood pressure stability were also sought. The degree of postural hypotension after treatment with phenoxybenzamine did not predict operative stability (r = -0.31, P = 0.33 Spearman). However, the peak total catecholamine level found during surgery correlated quite well with more operative instability (r = 0.65, P = 0.031, Spearman), suggesting that patients with phaeochromocytomas with high production of catecholamines are more likely to show cardiovascular instability.


What are the challenges faced by psychiatrists in the management of Alzheimer's disease?
Alzheimer's disease (AD) is a debilitating condition affecting millions of elderly citizens. The quality of life for AD patients significantly deteriorates in the face of worsening cognitive deficits and disabling functional declines, both contributing to manifestations of difficult behaviors. Of the estimated 4 million individuals with AD, only 60% of probable AD cases are diagnosed, with little more than half of those receiving treatment. One of the possible reasons for this problem is the large role primary care physicians (PCPs) have in diagnosing and treating AD. The barriers that PCPs confront to adequately manage these patients will be discussed. Finally, the specific challenges that geriatric psychiatrists will face in addressing these issues in an environment where there is only a limited number of trained geriatric psychiatrists will be discussed, as well as the possible role that new technology could have in finding the solution to this difficult problem.


Th2-dependent disappearance and phenotypic conversion of mouse alveolar macrophages.
Alveolar macrophages (alvMs) play an important role for maintenance of lung function by constant removal of cellular debris in the alveolar space. They further contribute to defense against microbial or viral infections and limit tissue damage during acute lung injury. alvMs arise from embryonic progenitor cells, seed the alveoli before birth, and have life-long self-renewing capacity. However, recruited monocytes may also help to restore the alvM population after depletion caused by toxins or influenza virus infection. At present, the population dynamics and cellular plasticity of alvMs during allergic lung inflammation is poorly defined. To address this point, we used a mouse model of Aspergillus fumigatus-induced allergic lung inflammation and observed that Th2-derived IL-4 and IL-13 caused almost complete disappearance of alvMs. This effect required STAT6 expression in alvMs and also occurred in various other settings of type 2 immunity-mediated lung inflammation or administration of IL-4 complexes to the lung. In addition, Th2 cells promoted conversion of alvMs to alternatively activated macrophages and multinucleated giant cells. Given the well-established role of alvMs for maintenance of lung function, this process may have implications for resolution of inflammation and tissue homeostasis in allergic asthma.


A preliminary integrated analysis of miRNA-mRNA expression profiles reveals a role of miR-146a-3p/TRAF6 in plasma from gestational diabetes mellitus patients.
To utilize an integrative strategy to construct functional miRNA-mRNA regulatory networks by combining the reverse expression relationships between miRNAs and targets and computational predictions for gestational diabetes mellitus (GDM). A total of three microarray or RNA-seq datasets (GSE98043, GSE19649 and GSE92772) of plasma samples comparing GDM pregnant women and healthy control pregnant women were downloaded from the GEO database. The differentially expressed genes (DEmRNAs) and the differentially expressed miRNAs (DEmiRNAs) was performed. The target genes of DEmiRNAs were identified using two independent and complementary types of information: computational target predictions and expression relationships. An interaction network was constructed to identify hub genes of GDM. Another dataset (GSE92772) was used to externally verify the predictive ability of the hub genes. A total of 264 DEmiRNAs and 1217 DEmRNAs were identified with Hsa-miR-146a-3p ranked first of DEmiRNAs. Functions of GDM-related miRNAs were mainly enriched in the glypican pathway, proteoglycan syndecan-mediated signaling events, and syndecan-1-mediated signaling events. A total of 47 target genes, including TRAF6, were shared between the computational target predictions and DEmRNAs and were identified as target genes of hsa-miR-146a-3p. The interaction network analysis identified TRAF6, CASP8, PTPN6, and CHD3 as hub genes involved in the pathophysiological process of GDM. Next, independent external validation was performed using the GSE19649 dataset. The expression of TRAF6, CASP8 and CHD3 in eight pairs of GDM blood samples was confirmed to be higher than that in healthy pregnant women blood samples with a AUC of 0.813, 0.813, and 0.703, respectively. Our preliminary analysis revealed that miR-146a-3p/TRAF6 might play a central role in the pathogenesis of GDM. Three hub genes, TRAF6, CASP8, and CHD3, were identified and independently externally validated as potential GDM noninvasive serum markers for future biomarkers research.


Calculating the number of undetected active SARS-CoV-2 infections from results of population-wide antigen tests.
Current European research estimates the number of undetected active SARS-CoV-2 infections (dark figure) to be two- to 130-fold the number of detected cases. We revisited the population-wide antigen tests in Slovakia and South Tyrol and calculated the dark figure of active cases in the vulnerable populations and the number of undetected active cases per detected active case at the time of the population-wide tests. Our analysis follows three steps: using the sensitivities and specificities of the used antigen tests, we first calculated the number of test-positive individuals and the proportion of actual positives in those who participated in the antigen tests. We then calculated the dark figure in the total population of Slovakia and South Tyrol, respectively. Finally, we calculated the ratio of the dark figure in the vulnerable population to the number of newly detected infections through PCR tests. Per one positive PCR result, another 0.15 to 0.71 cases must be added in South Tyrol and 0.01 to 1.25 cases in Slovakia. The dark figure was in both countries lower than assumed by earlier studies.


[The selection process in the Faculty of Medicine: the usefulness of a psychological and aptitude assessment].
In almost all the universities worldwide, the admission to the Faculty of Medicine is subject to a specific selection process. In most cases tests are used to assess the cognitive abilities of the candidates. However, a growing number of universities (particularly American and Canadian) is using a set of instruments to evaluate non-cognitive skills in addition to these tests. Among the most commonly used tools are included personal interviews, Multiple Mini Interview (MMI), Personal Quality Assessment (PQA). In Italy in the last decade increasing emphasis was placed on assessing students' attitudes through the use of orientation tests (given in classrooms or online fillable), as part of several projects that involve collaboration between secondary school and university. Nevertheless, the admission to the Faculty of Medicine does not yet provide a psychological and aptitude assessment, but relies exclusively on cognitive features. In a similar way to what is already the case with the selection of personnel in law enforcement agency, we propose a selection model that includes an assessment of psychological features and aptitudes of the candidates, as well as cognitive skills.


Fluorescein-based pI markers for capillary isoelectric focusing with laser-induced fluorescence detection.
We prepared a series of low-molecular-mass fluorescent ampholytes with narrow pI range. These fluorescein-based ampholytes are detection compatible with argon laser-induced fluorescence (LIF) detection. The selected properties, important for their routine use as fluorescent pI markers, were examined. The pI values of new fluorescein-based pI markers were determined by capillary isoelectric focusing (CIEF) using currently available low-molecular-mass pI markers for CIEF with photometric detection. The examples of CIEF with fluorometric detection of new compounds together with fluorescein isothiocyanate (FITC) derivatized proteins are presented.


Scanning electron microscopic study of the tongue in the owl (Strix uralensis).
The dorsal lingual surfaces of adult owl (Strix uralensis) were examined by scanning electron microscopy. The length of the tongue was about 2 cm. The tip of the tongue of the owl was bifid. Three parts were distinguished in the tongue of the owl: the apex, the body and the root of the tongue. The conical region between the lingual apex and lingual root was a very wide area. There were thread-shaped processes/cells of epithelium in the lingual apex. The small or large conical papillae were observed on the lingual body. The many openings of the lingual glands existed in the lingual body and lingual root.


Three bronze medals for Switzerland at the 45(th) International Chemistry Olympiad in Moscow, Russia.
A team of four students from Swiss high schools, selected in a national competition and accompanied by their mentors, represented their country at the 45(th) International Chemistry Olympiad (IChO) held in July 2013 in Moscow, Russia. The exceptional performances of Patrik Willi, Boris Stolz and Mario De Capitani in both practical and theoretical chemistry were rewarded by three bronze medals at the international level, reflecting their efforts during the year-long preparation prior to the competition.


SARS-CoV-2 and ORF3a: Nonsynonymous Mutations, Functional Domains, and Viral Pathogenesis.
The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. Our study aimed at determining the nonsynonymous mutations in the 3a protein in SARS-CoV-2 and determining and characterizing the protein's structure and spatial orientation in comparison to those of 3a in SARS-CoV. A total of 51 different nonsynonymous amino acid substitutions were detected in the 3a proteins among 2,782 SARS-CoV-2 strains. We observed microclonality within the ORF3a gene tree defined by nonsynonymous mutations separating the isolates into distinct subpopulations. We detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. The functional domains were linked to virulence, infectivity, ion channel formation, and virus release. Our study showed the importance of conserved functional domains across the species barrier and revealed the possible role of the 3a protein in the viral life cycle. Observations reported in this study merit experimental confirmation.IMPORTANCE At the surge of the coronavirus disease 2019 (COVID-19) pandemic, we detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. Our analysis showed that the functional domains were linked to virulence, infectivity, ion channel formation, and virus release in SARS-CoV-2 3a. Our study also revealed the functional importance of conserved domains across the species barrier. Observations reported in this study merit experimental confirmation.


[Research progress of lung natural killer cells and their roles in pulmonary diseases].
Lung natural killer (NK) cells can be classified into tissue-resident NK (trNK) cells and conventional NK (cNK) cells. Both trNK and cNK are composed of multiple subsets with unique phenotypes and functional characteristics. However, the phenotypic and functional differences between the two captured less attention. The features of trNK and cNK in the development, phenotypes and functions are sorted, and the interactions between NK cells and other immune cells in the lung are presented. Moreover, the latest research progress of lung NK cells in lung infections, tumors, transplantation, asthma and other diseases is particularly highlighted. It suggests that trNK cells may play a significant role, although lung NK cells are mainly composed of cNK. Further investigations of lung trNK and cNK cells will provide new insights into NK cell-based disease research.


[Effect of melatonin on p38MAPKsignaling pathway in rats with phosgene-induced lung injury].
To investigate the effect of melatonin (MT) on p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with phosgene-induced lung injury. Fifty specific pathogen-free male Sprague-Dawley rats were randomly divided into phosgene inhalation group, air control group, saline control group, MT treatment group, and SB203580 (specific inhibitor of p38 MAPK) group, with 10 mice in each group. All groups except the air control group were exposed to phosgene, and the animals were sacrificed 6 h later. Lung wet/dry weight (W/D) ratio and the content of malondialdehyde (MDA) and nitric oxide (NO) and activity of myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF) were measured. The qualitative and quantitative expression of p38 MAPK and phospho-p38 MAPK (p-p38) was measured by immunohistochemistry (IHC) and Western blot, respectively. Inducible nitric oxide synthase (iNOS) level in lung tissue was determined by Western blot. Compared with the air control group, the phosgene inhalation group had significantly increased lung W/D ratio and neutrophil count in BALF (P < 0.01); the MT treatment group had significantly lower neutrophil count and lung W/D ratio than the phosgene inhalation group (P < 0.05). IHC demonstrated that the air control group had relatively weak expression of p-p38 in lung tissue; the expression of p-p38 was significantly up-regulated after phosgene inhalation, and it was mainly distributed in infiltrating inflammatory cells and vascular endothelial cells, positive in the cytoplasm and nucleus of many cells. The distribution of p-p38-positive cells in the MT treatment and SB203580 groups was similar to that in the phosgene inhalation group, but the MT treatment and SB203580 groups had a significantly reduced number of cells with p-p38-positive nuclei and a significantly reduced intensity of p-p38 expression signals. The phosgene inhalation group had significantly increased content of MDA and NO and activity of MPO compared with the air control group (P < 0.01); the MT treatment and SB203580 groups had significantly reduced content of MDA and NO and activity of MPO compared with the phosgene inhalation group (P < 0.05), but had higher content of MDA and NO and activity of MPO than the air control group. The Western blot showed that the phosgene inhalation group had significantly increased expression of iNOS and p-p38 compared with the air control group (P < 0.01); the MT treatment and SB203580 groups had lower expression of iNOS and p-p38 than the phosgene inhalation group (P < 0.05). MT and SB203580 have a significant protective effect in rats with phosgene-induced lung injury, and the mechanism may be associated with scavenging free radicals and inhibiting activation of p38 MAPK and expression of iNOS.


The envelope of passive motion allowed by the capsular ligaments of the hip.
Laboratory data indicate the hip capsular ligaments prevent excessive range of motion, may protect the joint against adverse edge loading and contribute to synovial fluid replenishment at the cartilage surfaces of the joint. However, their repair after joint preserving or arthroplasty surgery is not routine. In order to restore their biomechanical function after hip surgery, the positions of the hip at which the ligaments engage together with their tensions when they engage is required. Nine cadaveric left hips without pathology were skeletonised except for the hip joint capsule and mounted in a six-degrees-of-freedom testing rig. A 5 N m torque was applied to all rotational degrees-of-freedom separately to quantify the passive restraint envelope throughout the available range of motion with the hip functionally loaded. The capsular ligaments allowed the hip to internally/externally rotate with a large range of un-resisted rotation (up to 50±10°) in mid-flexion and mid-ab/adduction but this was reduced towards the limits of flexion/extension and ab/adduction such that there was a near-zero slack region in some positions (p<0.014). The slack region was not symmetrical; the mid-slack point was found with internal rotation in extension and external rotation in flexion (p<0.001). The torsional stiffness of the capsular ligamentous restraint averaged 0.8±0.3 N m/° and was greater in positions where there were large slack regions. These data provide a target for restoration of normal capsular ligament tensions after joint preserving hip surgery. Ligament repair is technically demanding, particularly for arthroscopic procedures, but failing to restore their function may increase the risk of osteoarthritic degeneration.


A randomized controlled trial of brief and ultrabrief pulse right unilateral electroconvulsive therapy.
Some studies suggest better overall outcomes when right unilateral electroconvulsive therapy (RUL ECT) is given with an ultrabrief, rather than brief, pulse width. The aim of the study was to test if ultrabrief-pulse RUL ECT results in less cognitive side effects than brief- pulse RUL ECT, when given at doses which achieve comparable efficacy. One hundred and two participants were assigned to receive ultrabrief (at 8 times seizure threshold) or brief (at 5 times seizure threshold) pulse RUL ECT in a double-blind, randomized controlled trial. Blinded raters assessed mood and cognitive functioning over the ECT course. Efficacy outcomes were not found to be significantly different. The ultrabrief group showed less cognitive impairment immediately after a single session of ECT, and over the treatment course (autobiographical memory, orientation). In summary, when ultrabrief RUL ECT was given at a higher dosage than brief RUL ECT (8 versus 5 times seizure threshold), efficacy was comparable while cognitive impairment was less.


Complexation of cadmium and copper by fluvial humic matter and effects on their toxicity.
The effects of humic acids and fulvic acids isolated from the River Arno (Italy) on the bioavailability and toxicity of cadmium and copper were assessed in relation to changes in their speciation. Measurements of the complexing capacity of solutions containing these organic ligands were carried out by a titration procedure followed by DPASV and toxicity tests were carried out using lysosomes isolated from rat liver. The complexing capacity of the physiological medium containing about 13 mg/L of humic acids, expressed as ligand concentrations, was 0.30 and 0.072 micromol/L for cadmium and copper respectively; the corresponding conditional stability constants were 4.2 x 10(11) and 1.3 x 10(8) (mol/L)-1. The complexing capacities of the solution containing the same amount of fulvic acids were 0.33 and 0.164 micromol/L for cadmium and copper respectively, the conditional stability constants were 3.2 x 10(11) and 2.4 x 10(7) (mol/L)-1. The humic acids reduced the toxicity of cadmium by about 5 times: the EC50 changed from 4.4 to 20.4 micromol/L. The dose effect curve of copper presented a bi-sigmoid trend and two EC50 values can be determined: The EC50(1) in the presence of humic acids changed from 2.0 to 3.1 micromol/L, while the EC50(2) increased from 22.3 to 45.3 micromol/L. The fulvic acids reduced the cadmium toxicity by about the same amount as humic acids, from 4.4 to 18.6 micromol/L, but they had no effect on copper toxicity. Analysing the chemical speciation of cadmium and copper in the presence of humic components and under toxicity test conditions we can say that the appreciable decrease of EC50 is not related to changes in their speciation; we can hypothesize that this is due to different processes, as well as to blocking of the lysosomal membrane. On the basis of the shape of the dose-effect curves obtained for cadmium and copper respectively, we can say that the toxic effects of the two metals are different and we can hypothesize that copper could exercise its toxic activity by inhibiting the ATP-driven proton pump and the function of the Cl- selective channel.


Protective Effect of Meretrix meretrix Oligopeptides on High-Fat-Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice.
The present study investigated the effects of MMO (Meretrix meretrix oligopeptides) on mice fed a high-fat diet. Mice were fed either a normal control diet (NC) or a high-fat diet (HFD) without or with MMO (50 mg/kg or 250 mg/kg) for four weeks. Levels of ALT, AST, liver tissue GSH-Px, and SOD activities, MDA levels were measured using commercially available kits; HE staining was performed to analyze pathologic changes of the liver; a TEM assay was performed to measure the ultrastructural alterations of the mitochondria, and Western blotting was performed to detect the expression of gene proteins related to lipid metabolism, inflammation, and liver apoptosis. After six weeks, body weight, ALT, AST, and MDA levels were significantly increased, and GSH-Px levels and SOD activities were significantly decreased in the HFD control group compared with the NC group. Consumption of the HFD compared with the NC caused fatty liver abnormal mitochondria with loss of cristae, intramitochondrial granules, and a swollen and rarefied matrix. Administration of MMO significantly decreased body weight gain, and ALT, AST, and MDA levels; increased SOD activity and GSH-Px levels; alleviated fatty liver steatosis; decreased the early apoptosis population; downregulated SREBP-1c, Bax, Caspase-9, Caspase-3, TNF-α, and NF-κB protein levels; and upregulated PPAR-α, Bcl-2, and AMPK-α, compared with the HFD control group. MMO exhibited protective effects in mice with NAFLD by regulating the NF-κB anti-inflammation signaling pathways to inhibit inflammation, regulate AMPK-α, PPAR-α and SREBP-1c to improve lipid metabolism disorder, and regulate Bcl-2/Bax anti-apoptosis signaling pathways to prevent liver cell apoptosis. These results suggest that dietary supplementation with MMO ameliorates high-fat-diet-induced NAFLD.


Seadragon genome analysis provides insights into its phenotype and sex determination locus.
The iconic phenotype of seadragons includes leaf-like appendages, a toothless tubular mouth, and male pregnancy involving incubation of fertilized eggs on an open "brood patch." We de novo-sequenced male and female genomes of the common seadragon (Phyllopteryx taeniolatus) and its closely related species, the alligator pipefish (Syngnathoides biaculeatus). Transcription profiles from an evolutionary novelty, the leaf-like appendages, show that a set of genes typically involved in fin development have been co-opted as well as an enrichment of transcripts for potential tissue repair and immune defense genes. The zebrafish mutants for scpp5, which is lost in all syngnathids, were found to lack or have deformed pharyngeal teeth, supporting the hypothesis that the loss of scpp5 has contributed to the loss of teeth in syngnathids. A putative sex-determining locus encoding a male-specific amhr2y gene shared by common seadragon and alligator pipefish was identified.


Comparative studies on generalized transducing bacteriophages of Proteus mirabilis, phim and pi1.
Comparative studies were made on the generalized transducing bacteriophages of Proteus mirabilis phim (Nakaya and Rownd), pi1(Böhme), and a clear plaque-forming mutant phim-c, derived from phim. Electron microscopic observations revealed that these phages were morphologically identical, indicating that they belonged to the group C of Bradley's classification, or to the type C1 of Ackermann's classification. Phages phim and pi1 formed characteristic turbid plaques different from each other, and the plaques of pi1 were smaller in size than those of phim. The plaques of phage phim-c were clear and also were the largest in size among those studied. Average latent periods of phim and pi1 were 70 and 60 min, respectively. Average burst size was found to be 30 and 10 plaque-forming units per infected cell for phim and pi1, respectively. It was confirmed by cross neutralization tests that phim and pi1 differed serologically from each other. The host range of the two phages also differed, and phage phim was more sensitive to heat than pi1. These results indicate that phages phim and pi1 are different types of phages. Majority of the properties of phage phim-c were nearly identical with those of phage phim except that the multiplication of phim-c was more strongly inhibited by methylene blue than that of phim and pi1. Phage phim-c is considered to be a clear mutant of phim.


Anthelmintic niclosamide suppresses transcription of BCR-ABL fusion oncogene via disabling Sp1 and induces apoptosis in imatinib-resistant CML cells harboring T315I mutant.
Tyrosine kinase BCR-ABL fusion protein is the driver in patients with chronic myeloid leukemia (CML). The gate-keeper mutation T315I is the most challenging mutant due to its resistance to most tyrosine kinase inhibitors (TKIs). The third generation TKI ponatinib is the only effective TKI to treat CML patients harboring T315I-BCR-ABL mutation, but with high rate of major arterial thrombotic events. Alternative strategies to specifically target T315I-BCR-ABL are needed for the treatment of CML patients harboring such a mutation. Given that Sp1 is a fundamental transcriptional factor to positively regulate WT-BCR-ABL fusion oncogene, the purpose of this investigation was aimed at evaluating the anti-tumor activity and the underlying mechanism in terms of Sp1 regulational effect on the transcription of T315I-BCR-ABL fusion oncogene. Like in WT-BCR-ABL, we identified enrichment of Sp1 on the promoter of T315I-BCR-ABL fusion gene. Treatment of WT- and T315I-BCR-ABL-expressing CML cells by niclosamide diminished such an enrichment of Sp1, and decreased WT- and T315I-BCR-ABL transcription and its downstream signaling molecules such as STAT5 and Akt. Further, niclosamide significantly inhibited the proliferation and induced apoptosis through intrinsic pathway. The in vivo efficacy validation of p-niclosamide, a water soluble derivative of niclosamide, showed that p-niclosamide significantly inhibited the tumor burden of nude mice subcutaneously bearing T315I-BCR-ABL-expressing CML cells, and prolonged the survival of allografted leukemic mice harboring BaF3-T315I-BCR-ABL. We conclude that niclosamide is active against T315I-BCR-ABL-expressing cells, and may be a promising agent for CML patients regardless of T315I mutation status.


A generic concept for the implementation of medical image retrieval systems.
This work presents mechanisms to support the development and installation of content-based image retrieval in medical applications (IRMA). A strict separation of feature extraction, feature storage, feature comparison, and the user interfaces is suggested. The concept and implementation of a system following these guidelines is described. The system allows to reuse implemented components in different retrieval algorithms, which improves software quality, shortens the development cycle for applications, and allows to establish standardized end-user interfaces.


Disfranchisement, expulsion and persecution of pathologists in the Third Reich - A sociodemographic study.
This sociodemographic study focuses on the disenfranchisement, expulsion and persecution of pathologists in the Third Reich - a group that has, until now, received little systematic attention in scholarly research. The paper attempts to determine the number of pathologists who suffered persecution, the characteristics they shared, and the effects the repression had on their lives - both in the period from 1933 to 1945 and in the post-war period. The study is based on primary sources from numerous archives as well as on a systematic re-analysis of published secondary literature on the history of Nazi medicine. A total of 89 disenfranchised pathologists were identified and have been included. The vast majority of these pathologists (90%) were persecuted due to their Jewish ancestry or their relation to Jews. A good two-thirds of these pathologists were employed at a university until their disenfranchisement. For two-thirds of these pathologists (n = 62; 70%), documentation of emigration was found. Twenty-four pathologists remained in their home country; of these, five died in concentration camps and two others committed suicide. The preferred country for direct immigration was the United States (n = 19), followed by Great Britain (n = 13). Most of these pathologists were able to establish themselves professionally in their destination country, and little inclination to return to Germany after 1945 was shown. The reasons for this were a lack of career options in their home country, the lack of a welcoming culture among colleagues and universities, and the stigmatizing experiences of individual pathologists had during academic appointments and reparations proceedings in Germany. However, especially in recent decades and in part posthumously, these pathologists are being granted honorary, intangible recognition in Germany and Austria. Even though this recognition can no longer provide tangible reparations, it is nevertheless a sign of a gradual change in consciousness.


Effect of tumor necrosis factor alpha antagonists in a patient with rheumatoid arthritis and primary biliary cirrhosis.
The proinflammatory cytokine tumor necrosis factor alpha seems to play a major role in the pathogenesis of both rheumatoid arthritis and primary biliary cirrhosis. We describe the case of a 46-year-old female patient with rheumatoid arthritis and concomitant primary biliary cirrhosis treated with anti-tumor necrosis factor alpha agents. During infliximab treatment we observed a poor clinical response and persistence of liver function test abnormalities. After infliximab interruption the levels of alkaline phosphatase dropped and had nearly reached normal values when etanercept was started. This new therapeutic regimen was well tolerated with joint clinical improvement and normalization of alkaline phosphatase. This single case shows that etanercept therapy maintained liver enzymes within the normal range and controlled the arthritis with a 30-month follow-up whereas infliximab did not account for similar results.


Outcomes following coronary artery bypass grafting with multiple arterial grafting by pump status in men and women.
Multiple arterial grafting (MAG) and off-pump surgery are strategies proposed to improve outcomes with coronary artery bypass grafting (CABG). This study was conducted to determine the impact of off-pump surgery on outcomes after CABG with MAG in men and women. This cohort study used population-based data to identify all Ontarians undergoing isolated CABG with MAG between October 2008 and September 2019. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE; hospitalization for stroke, myocardial infarction hospitalization or heart failure, or repeat revascularization). Analysis used propensity-score overlap-weighted cause-specific Cox proportional hazard regression. A total of 2989 women (1188 off-pump, 1801 on-pump) and 16,209 men (6065 off-pump, 10,144 on-pump) underwent MAG with a median follow-up of 5.0 years (interquartile range, 2.7-8.0) years. Compared to the on-pump approach, all-cause mortality was not changed with off-pump status (hazard ratio [HR] in women: 1.25 [95% CI, 0.83-1.88]; in men: 1.08 [95% CI, 0.85-1.37]). In women, the risk of MACCE was significantly higher off-pump (HR, 1.45; 95% CI, 1.04-2.03), with nonsignificantly increased risk observed for all component outcomes. In patients undergoing CABG with MAG, this population-based analysis found no association between pump status and survival in either men or women. However, it did suggest that off-pump MAG in women may be associated with an increased risk of MACCE.


Myc tagging along the TRAIL to death receptor 5.
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL; also known as Apo2L) is an apoptotic cytokine that is being developed as a novel anticancer agent. TRAIL mediates its effect via death receptors 4 (DR4) and DR5 and appears to selectively induce apoptosis in cancer cells. The molecular basis of why normal cells seem to better tolerate this novel cytokine remains unknown. Recently, it has been reported that Myc oncoprotein by upregulating DR5 appears to augment cellular susceptibility to TRAIL and to DR5 agonistic antibodies. Several previous studies have already established that various clinically relevant agents by upregulating DR5 sensitize cells to TRAIL. However, the finding that DR5 is upregulated by an oncoprotein that is overexpressed in several tumor types is noteworthy and may spark future investigations aiming to explore the Myc and DR5 expression status of primary tumors and their ultimate vulnerability to DR5-targeted therapeutics.


Effects of foliage litter of a pioneer shrub (Artemisia halodendron) on germination from the soil seedbank in a semi-arid sandy grassland in China.
Vegetation recovery during succession is an important process for ecological restoration of the soil, especially in degraded sandy land. However, the driving mechanisms, such as how a pioneer species competes with other species, is uncertain. In China's Horqin Sandy Land, Artemisia halodendron is an important shrub that is common on semi-fixed dunes, where it replaces Agriophyllum squarrosum during succession, and is an important indicator species of the second stage of dune stabilization. However, how it outcompetes other species is still unclear. In this study, we conducted a seed bank germination experiment using soil from the native habitats of A. halodendron on semi-fixed dunes. We covered the soil with foliage litter of A. halodendron at a range of concentrations. Seed germination and seedling growth were strongly affected by the foliage litter. Seed germination and seedling growth were not harmed by a low concentration (≤50 g m-2) of the foliage litter but severely inhibited by high concentrations (≥100 g m-2). Strong allelopathy, indicated by decreased germination, increased seedling loss, and decreased plant biomass, appeared during the later stages of germination (after about 20 days of incubation). Our results suggest that as a pioneer shrub during the vegetation succession that occurs during dune stabilization, A. halodendron outcompeted other species through the allelopathic effect of its foliage litter. This helps to explain the patchy distribution and heterogeneity of vegetation communities in the Horqin Sandy Land.


Nodular fasciitis in the axillary tail of the breast.
Nodular fasciitis is a benign proliferation of myofibroblasts which presents clinically as a rapidly growing mass with nonspecific features on imaging and high cellular activity on histopathology. Nodular fasciitis can be mistaken for malignant fibrous lesions such as soft tissue sarcoma or breast carcinoma when located within breast tissue. This presents a problem for appropriate treatment planning as the natural history of nodular fasciitis is spontaneous regression. We present the mammographic, sonographic, computed tomography, and histopathologic characteristics of nodular fasciitis in a 68 year female initially presenting with a rapidly enlarging right axillary mass.


End-of-Life Care Challenges from Staff Viewpoints in Emergency Departments: Systematic Review.
The hospital emergency department (ED) is the place where people most commonly seek urgent care. The initial diagnosis of an end-of-life (EOL) condition may occur in the ED. In this review we described the challenges; from the staff members' perspectives, to safe, appropriate, and high quality end-of-life care (EOLC) for people who are diagnosed with non-malignant diseases who present to ED settings internationally. We conducted a systematic review of peer-reviewed literature. PubMed, Scopus, CINAHL, Medline, and Web of Science were searched from 2007 to 2017. In this review the challenges in providing quality EOLC from staff viewpoints, for EOL people who are diagnosed with non-malignant progressive diseases in ED settings, were classified into eight themes: (1) EOLC education and training, (2) ED design, (3) Lack of family support, (4) Work Load, (5) ED staff communication and decision making, (6) EOLC quality in ED, (7) resource availability (time, space, appropriate interdisciplinary personnel) and (8) integrating palliative care (PC) in ED. The formulation of EOLC using this review result may help to improve the quality of life for dying people by providing ED staff with clear guidelines that can guide them in their daily practice.


Self-assembled multi-component catenanes: structural insights into an adaptable class of molecular receptors and [2]-catenanes.
Under acidic conditions (50 equiv of TFA), combinations of hydrazide A-B monomers self-assemble into octameric [2]-catenanes with high selectivity for [1(3)2](2), where 1 is a D-Pro-X (X = Aib, Ac(4)c, Ac(6)c, L-4-Cl-PhGly)-derived monomer and 2 is an L-Pro'-L-arylGly (Pro' = Pro, trans-F-Pro, trans-HO-Pro, aryl = naphthyl, phenyl)-derived monomer. Five different combinations of monomers were studied by X-ray crystallography. In each case, the unique aryl glycine unit is located in the core of the structure where the aryl ring templates a CH-π-CH sandwich. Analysis of metrical parameters indicates that this core region is highly conserved, while the more peripheral zones are flexible. (1)H NMR spectroscopy indicate that the solid-state structures are largely retained in solution, though several non-C(2)-symmetric compounds have a net C(2)-symmetry that indicates accessible dynamic processes. Catenane dynamic processes were additionally probed through H/D exchange, with the core being inflexible relative to the peripheral structure. Mass spectrometry was utilized to identify the constitutional isomerism in the minor asymmetric [1(5)2(3)] catenanes.


Self-reported sleep in late pregnancy in relation to birth size and fetal distress: the E Moe, Māmā prospective cohort study.
To explore associations between features of sleep during pregnancy and adverse outcomes for the infant. E Moe, Māmā is a cohort study in Aotearoa/New Zealand that investigates self-reported sleep and maternal health in late pregnancy and the postpartum period. Women (N=633; 194 Māori) reported detailed information on their sleep duration, quality, disturbances, disorders (snoring, breathing pauses, twitching legs, restless legs) and daytime sleepiness between 35 and 37 weeks gestation. Birthweight and fetal distress during labour were extracted from medical records. Associations between each sleep variable and small or large for gestational age (SGA/LGA) using customised birthweight centile or fetal distress were estimated using multinomial/logistic regression, controlling for potential confounders. Secondary analyses considered differences in associations between Māori and non-Māori women. There was some indication that breathing pauses (a measure of sleep apnoea) were associated with both SGA (OR 2.8, 95% CI 0.9 to 9.0, p=0.08) and LGA (OR 2.0, 95% CI 0.7 to 5.7, p=0.20), with the association for LGA being stronger when only pregnancy-onset breathing pauses were considered (OR 3.5, 95% CI 1.3 to 9.6, p=0.01). There was also some evidence that pregnancy-onset leg twitching (OR 3.3, 95% CI 1.1 to 10.0, p=0.03) and frequent sleep disturbance due to feeling too hot or too cold (OR 1.7, 95% CI 0.9 to 3.6, p=0.13) were associated with higher risk of fetal distress. Other sleep measures, including snoring, were not associated with SGA, LGA or fetal distress. Many of the associations we observed were considerably stronger in Māori compared with non-Māori women. We did not find evidence of previously reported associations between snoring and SGA. Our findings tentatively suggest that self-reported breathing pauses and leg twitching in late pregnancy are associated with infant outcomes, and highlight ethnic inequalities.


High-performance Cu nanoparticles/three-dimensional graphene/Ni foam hybrid for catalytic and sensing applications.
A novel hybrid of Cu nanoparticles/three-dimensional graphene/Ni foam (Cu NPs/3DGr/NiF) was prepared by chemical vapor deposition, followed by a galvanic displacement reaction in Ni- and Cu-ion-containing salt solution through a one-step reaction. The as-prepared Cu NPs/3DGr/NiF hybrid is uniform, stable, recyclable and exhibits an extraordinarily high catalytic efficiency for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) with a reduction rate constant K = 0.056 15 s-1, required time ∼30 s and excellent sensing properties for the non-enzymatic amperometric hydrogen peroxide (H2O2) with a linear range ∼50 μM-9.65 mM, response time ∼3 s, detection limit ∼1 μM. The results indicate that the as-prepared Cu NPs/3DGr/NiF hybrid can be used to replace expensive noble metals in catalysis and sensing applications.


Diagnostic front end for BESSY II.
For BESSY II, synchrotron radiation beam diagnostics will be incorporated in both the insertion-device front ends and the dipole-beamline front ends. In order to gain a complete picture of the source characteristics, a diagnostic front end has been designed and tested for dipole radiation. This consists of (i) a pinhole array imaging system, (ii) a double-blade system for the determination of the vertical center of gravity of the synchrotron radiation fan, and (iii) a Bragg-Fresnel multilayer system for the most precise image information about the source size and shape.


Gender-based violence: concepts, methods, and findings.
The United Nations has identified gender-based violence against women as a global health and development issue, and a host of policies, public education, and action programs aimed at reducing gender-based violence have been undertaken around the world. This article highlights new conceptualizations, methodological issues, and selected research findings that can inform such activities. In addition to describing recent research findings that document relationships between gender, power, sexuality, and intimate violence cross-nationally, it identifies cultural factors, including linkages between sex and violence through media images that may increase women's risk for violence, and profiles a host of negative physical, mental, and behavioral health outcomes associated with victimization including unwanted pregnancy and abortion. More research is needed to identify the causes, dynamics, and outcomes of gender-based violence, including media effects, and to articulate how different forms of such violence vary in outcomes depending on cultural context.


Trace and major elements in whole blood, serum, cerebrospinal fluid and urine of patients with Parkinson's disease.
Quantifications of Al, Ca, Cu, Fe, Mg, Mn, Si and Zn were performed in urine, serum, blood and cerebrospinal fluid (CSF) of 26 patients affected by Parkinson's disease (PD) and 13 age-matched controls to ascertain the potential role of biological fluids as markers for this pathology. Analyses were performed by Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field Inductively Coupled Plasma Mass Spectrometry. The serum oxidant status (SOS) and anti-oxidant capacity (SAC) were also determined. Results showed a decreasing trend for Al in all the fluids of PD patients, with the strongest evidence in serum. Calcium levels in urine, serum and blood of PD patients were significantly higher than in controls. Copper and Mg concentrations were significantly lower in serum of PD patients. Levels of Fe in urine, blood and CSF of patients and controls were dissimilar, with an increase in the first two matrices and a decrease in CSF. No significant difference was found in levels of Mn between patients and controls. Urinary excretion of Si was significantly higher in PD subjects than in controls. No clear difference between Zn levels in the two groups was found for serum, urine or CSF, but an increase in Zn levels in the blood of PD patients was observed. The SOS level in PD was significantly higher while the corresponding SAC was found to be lower in patients than in controls, in line with the hypothesis that oxidative damage is a key factor in the pathogenesis of PD. The results on the whole indicate the involvement of Fe and Zn (increased concentration in blood) as well as of Cu (decreased serum level) in PD. The augmented levels of Ca and Mg in the fluids and of Si in urine of patients may suggest an involuntary intake of these elements during therapy.


Phenobarbital versus clonazepam for sedative-hypnotic taper in chronic pain patients. A pilot study.
A randomized, double-blind controlled trial is reported comparing phenobarbital and clonazepam for the purpose of sedative-hypnotic taper in inpatients with chronic, nonmalignant pain. After receiving the Minnesota Multiphasic Personality Inventory (MMPI) and a standardized psychiatric diagnostic interview, patients' baseline sedative-hypnotic use was assessed over 48 hours. Baseline use was converted into phenobarbital or clonazepam equivalents and administered in four doses daily using a blinded liquid pain cocktail. Baseline dose was maintained for two days and then tapered by 10% per day. Over the first week of taper, differences in mean and maximum Beck Anxiety and Benzodiazepine Withdrawal scores were not significant. However, when scales 1, 3, or 8 of the MMPI were taken as covariates, differences on the Withdrawal Scale only increased to a trend level for mean scores and to a significant level for maximum scores. These findings support the superiority of benzodiazepines over barbiturates for sedative-hypnotic taper for symptoms of withdrawal but not of recurrent or rebound anxiety.


Antimalarial phenanthrene amino alcohols. 3. Halogen-containing 9-phenanthrenemethanols.
A series of new 9-phenanthrene amino alcohols has been prepared in which each compound bears from one to five halogen or halogen-containing moieties. A number of these compounds are extremely active against Plasmodium berghei in the mouse. Some structural requirements for optimal efficacy are considered.


Assessment of the diet quality of US adults in the Lower Mississippi Delta.
The Lower Mississippi Delta (LMD) is a region at high risk of nutritionally related diseases. Assessing LMD diet quality is important in policy making, monitoring service outcomes, and designing sustainable research interventions. The purpose was to assess the diet quality of LMD adults by using the Healthy Eating Index (HEI) to 1) identify potential and needed interventions, 2) determine population subgroups needing special attention, and 3) compare regional intakes with national intakes. Data were obtained from a representative cross-sectional telephone survey (n = 1699), Foods of our Delta Study 2000, by using the US Department of Agriculture's multiple-pass 24-h recall methodology and random-digital-assisted dialing with selection of one adult per household. The diet quality of LMD adults was compared with that of white and African American adults in the National Health and Nutrition Examination Survey (NHANES), 1999-2000. Age, race, and income of LMD adults affected overall diet quality. African Americans had lower grain, vegetable, milk, and variety scores than did whites. The consumption of grains and vegetables was associated with lower odds ratios for being overweight. The LMD adults had a lower HEI score than did the adults in NHANES 1999-2000 (60.1 compared with 63.4), and more LMD adults ate a poor diet (24.8% compared with 18.3%). Low-income and young-adult households in the LMD are in need of nutrition interventions with an emphasis on increasing grain, fruit, and vegetable intakes. Because socioeconomic factors affect diet quality, a multimodal, longitudinal approach appears needed to improve nutritional health.


Erectile dysfunction in cirrhosis is impacted by liver dysfunction, portal hypertension, diabetes and arterial hypertension.
Although several risk factors for erectile dysfunction may be present in patients with cirrhosis, data on the actual prevalence and cause of erectile dysfunction is limited. The International Index of Erectile Function-5 (IIEF-5) is a well-validated survey to determine the presence and severity of erectile dysfunction in men. We assessed (i) the prevalence and severity of erectile dysfunction, and (ii) risk factors for erectile dysfunction in patients with cirrhosis. In this prospective study, erectile dysfunction was defined as: absent (>21 IIEF-5-points), mild (12-21) and severe (5-11). Patients with overt hepatic encephalopathy, active alcohol abuse, extrahepatic malignancy, previous urologic surgery, previous liver transplantation and severe cardiac conditions were excluded. Among n = 151 screened patients, n = 41 met exclusion criteria and n = 30 were sexually inactive. Thus, a final number of n = 80 male patients with cirrhosis were included. Patient characteristics: age: 53 ± 9 years; model for end-stage liver disease score (MELD): 12.7 ± 3.9; Child-Pugh score (CPS) A: 30 (37.5%), B: 35 (43.8%), C: 15 (18.7%); alcohol: 38 (47.5%), viral: 25 (31.3%), alcohol/viral: 7 (8.8%) and others: 10 (12.5%). The presence of erectile dysfunction was found in 51 (63.8%) patients with 44 (55%) and 7 (8.8%) suffering from mild-to-moderate and moderate-to-severe erectile dysfunction. Mean MELD and hepatic venous pressure gradient (HVPG) were significantly higher in patients with erectile dysfunction (P = .021; P = .028). Child-Pugh score C, MELD, creatinine, age, arterial hypertension, diabetes, low libido, low testosterone and high HVPG were associated with the presence of erectile dysfunction. Interestingly, beta-blocker therapy was not associated with an increased risk. In multivariate models, arterial hypertension (OR: 6.36 [1.16-34.85]; P = .033), diabetes (OR: 7.40 [1.31-41.75]; P = .023), MELD (OR: 1.19 [1.03-1.36]; P = .015) and increasing HVPG (n = 48; OR: 1.11 [1.002-1.23]; P = .045) were independent risk factors for the presence of erectile dysfunction. About two-thirds of male patients with cirrhosis show erectile dysfunction. Severity of liver dysfunction, portal hypertension, arterial hypertension and diabetes were identified as risk factors for erectile dysfunction.


Triterpenoids.
This review covers the isolation and structure determination of triterpenoids including squalene derivatives, lanostanes, cycloartanes, dammaranes, euphanes, tirucallanes, tetranortriterpenoids, quassinoids, lupanes, oleannes, friedelanes, ursanes, hopanes, isomalabaricanes and saponins. The literature from January to December 2002 is reviewed and 221 references are used.


Is amelogenesis imperfecta an indication for renal examination?
The term 'amelogenesis imperfecta' (AI) describes a diverse group of hereditary conditions primarily affecting the quality and/or quantity of dental enamel. This paper describes a case in which hypoplastic AI with delayed/failure of eruption of the permanent teeth was shown to be associated with renal calcification. Given the importance of the renal involvement, the authors suggest that paediatric dentists consider referring all children with this dental phenotype for renal ultrasound examination.


[Cytomegalovirus-associated haemophagocytic syndrome and acute renal failure in a patient with chronic lymphocytic leukaemia].
A 60-year-old man with chronic lymphocytic leukaemia was admitted to our department with fever and hepatospleno-megaly. Laboratory findings revealed hyperferritinaemia of 40,300 microgram/l and both liver and renal dysfunction. A bone marrow biopsy showed haemophagocytosis consistent with haemophagocytic syndrome. The serology was compatible with acute Cytomegalovirus infection. The patient received therapy with ganciclovir, prednisolone and gamma globulin, and the acute renal failure was treated with haemodialysis. The patient responded well to the treatment and was discharged after a month with normal lever and renal function.


Benign breast disease: when to treat, when to reassure, when to refer.
Many women have breast symptoms-swelling and tenderness, nodularity, pain, palpable lumps, nipple discharge, or breast infections and inflammation. Fortunately, relatively few have breast cancer. Physicians must distinguish benign breast conditions from malignant ones, and know when to refer the patient to a specialist. We have included some of the newer diagnostic techniques and the approach to patients with nonpalpable lesions detected on a screening mammogram.


Effects of brain-derived neurotrophic factor-catecholamine-O-methyltransferase gene interaction on schizophrenic symptoms.
The methionine variant of Val66Met brain-derived neurotrophic factor BDNF met and catecholamine-O-methyltransferase (COMT L) is associated with a deficit in attention and aggravation of delusions in schizophrenia. We hypothesized that the BDNF-COMT gene interaction would affect the symptoms and cognition in schizophrenia. Ninety-six schizophrenic patients and 79 control participants were recruited. The patients who were BDNF met/met x COMT L carriers had the highest scores of delusion of Positive Symptoms and the Scale for Assessment of Negative Symptoms, word reading of the color word test, and trail-making test B time, compared with the other three genotype interactions. The current results suggest that patients with the BDNF met/met x COMT L allele had more delusional symptoms and poorer cognitive flexibility, compared with the other three genotype interactions.


Clinical Correlates of Cerebral Amyloid Deposition in Parkinson's Disease Dementia: Evidence from a PET Study.
Dementia in Parkinson's disease (PDD) is common presumably due to combined neuropathological substrates. Amyloid-β (Aβ) plaques are well described in PDD but their contribution in synucleinopathies is still controversial. To investigate regional [18F]Florbetapir binding and its relative contribution to cognitive dysfunction in a cohort of PDD patients and to test whether PDD patients with comorbid amyloidopathy have different clinical and neuropsychological characteristics. 21 PDD patients, 20 with Alzheimer's disease (AD), and 9 control subjects underwent amyloid positron emission tomography (PET) imaging, neurological, and neuropsychological assessment. Radioligand binding was compared across the groups. PDD scans were interpreted qualitatively and semiquantitatively and categorized as positive or negative. Annual longitudinal Mini-Mental State Examination (MMSE) of PDD subjects was retrospectively collected in order to relate Aβ burden to the course of cognitive impairment. [18F]Florbetapir PET imaging was positive in 11 PDD patients (52.38%) using the semi-quantitative method. There were no group differences between PDD subjects with increased cortical [18F]Florbetapir (+) and those without (-), according to demographic and clinical parameters. PDD+ performed worse on Digit Span Foward and on Rey Auditory Verbal Learning Test delayed recall than the PDD- with a significant negative correlation between global cortical retention and specific memory tests. Aβ load did not correlate with MMSE ratings although PDD+ demonstrated a faster clinical progression of dementia. Significant Aβ deposition is common in PDD patients contributing to memory impairment and driving a faster rate of cognitive decline.


SARS-CoV-2 Outbreak on a Spanish Mink Farm: Epidemiological, Molecular, and Pathological Studies.
Farmed minks have been reported to be highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may represent a risk to humans. In this study, we describe the first outbreak of SARS-CoV-2 occurred on a mink farm in Spain, between June and July 2020, involving 92,700 animals. The outbreak started shortly after some farm workers became seropositive for SARS-CoV-2. Minks showed no clinical signs compatible with SARS-CoV-2 infection throughout the outbreak. Samples from 98 minks were collected for histopathological, serological, and molecular studies. Twenty out of 98 (20.4%) minks were positive by RT-qPCR and 82 out 92 (89%) seroconverted. This finding may reflect a rapid spread of the virus at the farm with most of the animals overcoming the infection. Additionally, SARS-CoV-2 was detected by RT-qPCR in 30% of brain samples from positive minks. Sequencing analysis showed that the mink sequences were not closely related with the other mink SARS-CoV-2 sequences available, and that this mink outbreak has its probable origin in one of the genetic variants that were prevalent in Spain during the first COVID-19 epidemic wave. Histological studies revealed bronchointerstitial pneumonia in some animals. Immunostaining of viral nucleocapsid was also observed in nasal turbinate tissue. Farmed minks could therefore constitute an important SARS-CoV-2 reservoir, contributing to virus spread among minks and humans. Consequently, continuous surveillance of mink farms is needed.


Lectins in cancer cells.
Studies carried out over the last few years have demonstrated that tumor cells and malignant tissues contain lectins that are similar in sugar-binding specificity, molecular size, and antigenicity to the lectins found in normal cells and tissues. Lectins from tumor cells also share marked sequence homology with lectins from normal tissues. Lectins were purified from various tumor cells by affinity chromatography and monoclonal and polyclonal antilectin antibodies were prepared against them. These enabled us to establish the following: (1) Lectins are present on the surface of all the tumor cells that were examined, albeit at varying levels. (2) The level of cell surface lectins increases after normal cells are transformed by transfection with certain oncogenes or by retroviruses, or when cells transformed with a temperature-sensitive viral mutant are switched from growth at the nonpermissive to the permissive temperature. (3) Among tumor cells differing in metastatic propensity, those exhibiting a higher potential express higher levels of surface lectins. (4) Tumor cell surface lectins might be involved in cell-cell adhesion, cell attachment to substratum, the expression of the transformed phenotype (anchorage-independent growth), and blood-borne metastasis. (5) The levels of the lectins in tumor cells are modulated by agents that suppress the transformed phenotype (as represented by anchorage-independence) or enhance differentiation. Numerous studies by others have shown that cell surface carbohydrate-containing molecules are modified after transformation, and our findings demonstrate that the expression of cell surface carbohydrate-binding proteins is also altered by transformation. Obviously, any of these changes may result in alterations in cellular interactions. All the above findings implicate tumor cell lectins in cellular interactions (adhesion, attachment, possible binding of exogenous soluble glycoconjugates), cell growth and anchorage-independent growth, malignant transformation, tumor cell differentiation, and metastasis. It is clear that even if these lectins are involved in only a few of these fundamental processes, it is important to elucidate their functions and the mechanisms by which their expression is regulated during neoplastic transformation and tumor progression and the suppression of the transformed phenotype.


A heteroleptic fused bi-cuboctahedral Cu21S2 cluster.
A new dicationic cluster, [Cu21S2{S2CNnBu2}9(C2Ph)6]2+, where the Cu21S2 kernel consists of two S@Cu12 cuboctahedra sharing a triangular Cu3 face is reported. Its waist part is bridged by three dithiocarbamate ligands, each in a hexaconnective, hexametallic (μ3, μ3) coordination pattern, an unprecedented feature in Cu nanocluster chemistry.


Class-specific determination of fluoroquinolones based on a novel chemiluminescence system with molecularly imprinted polymers.
A ultrasensitive chemiluminescence (CL) method for the determination of fluoroquinolones (FQs) in milk was proposed based on the enhancement effect of FQs on the CL reaction between cerium(IV) and methoxylated Cypridina luciferin analogs (MCLA). Prior to the CL determination, molecularly imprinted polymers (MIPs) with superior recognition performances were adopted to the clean-up and extraction of the family of FQs. Then the developed CL system coupling with MIPs (MIP-CL) was applied to the selective determination of FQs in milk. Under the optimized conditions, the method was validated with respect to linearity, precision, accuracy, limits of detection and quantification. The relative standard deviation (RSD) on intra-day assay was below 5.1%, and detection limit was as low as 0.10 nmol/L. The consistency of this method and HPLC method was compared and validated by the paired t-test. The results indicated that the proposed method allowed class-specific determination of FQs in complex matrices.


Importation of chloroplast proteins under heat stress is facilitated by their SUMO conjugations.
Chloroplasts are hypersensitive to heat stress (HS). SUMOylation, a critical post-translational modification, is conservatively involved in HS responses. However, the functional connection between SUMOylation and chloroplasts under HS remains to be studied. The bioinformatics, biochemistry, and cell biology analyses were used to detect the SUMOylation statuses of Arabidopsis nuclear-encoded chloroplast proteins and the effect of SUMOylation on subcellular localization of these proteins under HS. PSBR, a subunit of photosystem II, was used as an example for a detailed investigation of functional mechanisms. After a global SUMOylation site prediction of nuclear-encoded chloroplast proteins, biochemical data showed that most of the selected candidates are modified by SUMO3 in the cytoplasm. The chloroplast localization of these SUMOylation targets under long-term HS is partially maintained by the SUMO ligase AtSIZ1. The HS-induced SUMOylation on PSBR contributes to the maintenance of its chloroplast localization, which is dependent on its chloroplast importation efficiency correlated to phosphorylation. The complementation analysis provided evidence that SUMOylation is essential for the physiological function of PSBR under HS. Our study illustrated a general regulatory mechanism of SUMOylation in maintaining the chloroplast protein importation during HS and provided hints for further investigation on protein modifications associated with plant organelles under stress conditions.


Preprotein translocase of the outer mitochondrial membrane: reconstituted Tom40 forms a characteristic TOM pore.
Tom40 is the central pore-forming component of the translocase of the outer mitochondrial membrane (TOM complex). Different views exist about the secondary structure and electrophysiological characteristics of Tom40 from Saccharomyces cerevisiae and Neurospora crassa. We have directly compared expressed and renatured Tom40 from both species and find a high content of beta-structure in circular dichroism measurements in agreement with refined secondary structure predictions. The electrophysiological characterization of renatured Tom40 reveals the same characteristics as the purified TOM complex or mitochondrial outer membrane vesicles, with two exceptions. The total conductance of the TOM complex and outer membrane vesicles is twofold higher than the total conductance of renatured Tom40, consistent with the presence of two TOM pores. TOM complex and outer membrane vesicles possess a strongly enhanced sensitivity to a mitochondrial presequence compared to Tom40 alone, in agreement with the presence of several presequence binding sites in the TOM complex, suggesting a role of the non-channel Tom proteins in regulating channel activity.


Bleeding-Source Exploration in Subdural Hematoma: Observational Study on the Usefulness of Postmortem Computed Tomography Angiography.
In a few cases, postmortem computed tomography angiography (PMCTA) is effective in postmortem detection of cortical artery rupture causing subdural hematoma (SDH), which is difficult to detect at autopsy. Here, we explore the usefulness and limitations of PMCTA in detecting the sites of cortical arterial rupture for SDH. In 6 of 10 cases, extravascular leakage of contrast material at nine different places enabled PMCTA to identify cortical arterial rupture. PMCTA did not induce destructive arterial artifacts, which often occur during autopsy. We found that, although not in all cases, PMCTA could show the site of cortical arterial rupture causing subdural hematoma in some cases. This technique is beneficial for cases of SDH autopsy, as it can be performed nondestructively and before destructive artifacts from the autopsy occur.


Paediatric malaria: What do paediatricians need to know?
Although malaria is principally a disease of the tropical and subtropical regions of the world, it is an important disease to be familiar with for both local and global reasons. It remains to be one of the most important infectious diseases of the world, particularly in sub-Saharan Africa, killing more than one million people - mostly children - every year. In Canada, at least 350 to 1100 imported cases are reported annually, 25% of which are in the paediatric age group, as a result of both travel and migration. Because malaria is a potentially severe and sometimes fatal disease that is unfamiliar to many paediatricians in Canada, it is important that clinicians become familiar with its clinical presentation; understand when it should be suspected; and have an approach to prompt diagnosis, appropriate treatment and effective prevention methods.


Effect of Pulse Energy, Pulse Frequency, and Tip Diameter on Intracanal Vaporized Bubble Kinetics and Apical Pressure During Laser-Activated Irrigation Using Er:YAG Laser.
Objective: Er:YAG laser-activated irrigation (LAI) is an effective method of root canal cleaning, but irrigant extrusion from the apical foramen has been a concern. We aimed to analyze the effects of pulse energy, pulse frequency, and laser tip diameter on intracanal vapor bubble kinetics and periapical pressure generation during LAI with Er:YAG laser. Background: Irrigant vapor bubble kinetics are one of indices of root canal cleaning efficacy. However, few studies have compared laser pulse conditions to vapor bubble kinetics, in relation to periapical pressure. Methods: A plastic root canal model (apical diameter 0.50 mm, 6% taper, 20 mm long) was filled with distilled water, and LAI with Er:YAG laser (Erwin AdvErl Unit; 30, 50, or 70 mJ; 10, or 20 pulses per second; laser tip R200T or R600T) was performed with the end of the tip fixed at 15 mm from the root apex. The number, maximum diameter, and velocity of vapor bubbles were analyzed by high-speed video imaging. Pressure generated outside the apical foramen was measured with a pressure sensor. Results: Vapor bubble count and maximum diameter increased significantly with pulse energy, pulse frequency, and tip diameter. Vapor bubble velocity increased significantly with pulse frequency, but not with pulse energy or tip diameter. Periapical pressure increased significantly with pulse energy, pulse frequency, and tip diameter. Conclusions: The pulse frequency was the single factor that significantly affected all the examined parameters (the number, diameter, and velocity) of vapor bubble kinetics together with the periapical pressure.


Terrien, a metabolite made by Aspergillus terreus, has activity against Cryptococcus neoformans.
Antimicrobial compounds, including antibiotics, have been a cornerstone of modern medicine being able to both treat infections and prevent infections in at-risk people, including those who are immune-compromised and those undergoing routine surgical procedures. Their intense use, including in people, animals, and plants, has led to an increase in the incidence of resistant bacteria and fungi, resulting in a desperate need for novel antimicrobial compounds with new mechanisms of action. Many antimicrobial compounds in current use originate from microbial sources, such as penicillin from the fungus Penicillium chrysogenum (renamed by some as P. rubens). Through a collaboration with Aotearoa New Zealand Crown Research Institute Manaaki Whenua-Landcare Research we have access to a collection of thousands of fungal cultures known as the International Collection of Microorganisms from Plants (ICMP). The ICMP contains both known and novel species which have not been extensively tested for their antimicrobial activity. Initial screening of ICMP isolates for activity against Escherichia coli and Staphylococcus aureus directed our interest towards ICMP 477, an isolate of the soil-inhabiting fungus, Aspergillus terreus. In our investigation of the secondary metabolites of A. terreus, through extraction, fractionation, and purification, we isolated nine known natural products. We evaluated the biological activity of selected compounds against various bacteria and fungi and discovered that terrein (1) has potent activity against the important human pathogen Cryptococcus neoformans.


[Novelties in surgery in 2016].
The year 2016 allowed further implementation of previous years innovations with the PIPAC treatment for peritoneal carcinomatosis, the development of new surgical technologies and procedures and challenging general principles in general and digestive surgery, including cholecystectomy and appendectomy. Prevention, improved general and perioperative care (ERAS program) become an integral part of our standard surgical activity.


Longitudinal autoantibody responses against tumor-associated antigens decrease in breast cancer patients according to treatment modality.
Metastatic breast cancer (BCa) is most often diagnosed months after completion of treatment of the primary tumor when a patient reports physical symptoms. Besides a physical examination, no other alternative recurrence screening method is recommended for routine follow-up care. Detection of autoantibodies against tumor-associated antigens (TAAs) has demonstrated promise for distinguishing healthy women from patients diagnosed with primary BCa. However, it is unknown what changes occur to patient autoantibody levels during and after treatment. Three serial blood draws were collected from 200 BCa patients: before treatment, 6 and 12 months after surgery. Patients were categorized according to treatment regimen, including surgery, chemotherapy, radiation, trastuzumab and hormonal therapies. The longitudinal samples were assayed for autoantibody responses against 32 conformation-carrying TAAs using a Luminex multiplex bead assay. The treatment modality groups that had the greatest decrease in autoantibody response levels were radiation + hormonal therapy; radiation + chemotherapy; and radiation + hormonal therapy + chemotherapy. For these three treatment groups, autoantibody responses against 9 TAAs (A1AT, ANGPTL4, CAPC, CST2, DKK1, GFRA1, GRN, LGALS3 and LRP10) were significantly reduced at 12 months after surgery compared to before treatment. One TAA, GRP78, had a significantly increased autoantibody response after 12 months. Single treatment regimens alone did not significantly alter autoantibodies levels against the studied TAAs. Radiation treatment was the common denominator of the three most affected groups for significant changes in autoantibody response levels.


Immunofluorescence study of cutaneous blood vessels of 16 patients with systemic lupus erythematosus.
In 16 patients with systemic lupus erythematosus, blood vessels in the affected region of the skin were examined regarding localization of immune complexes. Deposition of IgG, IgA, IgM, IgE, beta 1C and fibrin in the vessel walls was more frequently observed in intramural and perivascular sites than in intimal sites. IgM and fibrin were usually detected in intramural sites only. In large caliber arteries of the skin the intima was the main site of deposition of immune reactants, whereas, in small-caliber vessels, including capillaries, immune reactants were more often found in intramural and perivascular sites.


Activity of Extracts from Submerged Cultured Mycelium of Winter Mushroom, Flammulina velutipes (Agaricomycetes), on the Immune System In Vitro.
Extracts from submerged cultured mycelium of two strains of Flammulina velutipes, a popular culinary mushroom, were obtained by ultrasound and tested in vitro to determine their activity in innate immunity (monocytes/ macrophages). In addition, polyclonal antibodies against the extracts were produced. Both extracts have similar glycoproteins that contain mannose and glucose but have different glycoproteins with galactoseamine units. Two novel immunogenic glycoproteins with molecular weights of 32 and 25 kDa have been revealed. It is thought that these proteins are produced only by submerged cultured mycelium. Both extracts show immune-enhancing activity based on the significant modification of various parameters such as cytokine production, phagocytosis, and reactive oxygen species production.


Development and Validation of an Analytical Methodology Based on Liquid Chromatography-Electrospray Tandem Mass Spectrometry for the Simultaneous Determination of Phenolic Compounds in Olive Leaf Extract.
A simple method was validated for the analysis of 31 phenolic compounds using liquid chromatography-electrospray tandem mass spectrometry. Proposed method was successfully applied to the determination of phenolic compounds in an olive leaf extract and 24 compounds were analyzed quantitatively. Olive biophenols were extracted from olive leaves by using microwave-assisted extraction with acceptable recovery values between 78.1 and 108.7%. Good linearities were obtained with correlation coefficients over 0.9916 from calibration curves of the phenolic compounds. The limits of quantifications were from 0.14 to 3.2 μg g-1. Intra-day and inter-day precision studies indicated that the proposed method was repeatable. As a result, it was confirmed that the proposed method was highly reliable for determination of the phenolic species in olive leaf extracts.


Intraperitoneal insulin regimens and diabetic nephropathy.
Five patients with severe diabetic nephropathy (SN) and six patients with moderate diabetic nephropathy (MN) have been treated with intraperitoneal (i.p.) insulin administered by multiple injections. The five SN patients progressed to end-stage kidney disease. The six MN patients (five of whom are described) show stabilisation (and in two cases possibly some improvement) of renal function over time intervals ranging from eight to 23 months.


Effect of reserpine upon the haemodynamic course of recovery following experimental myocardial infarction.
Acute haemodynamic consequences of coronary artery ligation were evaluated in twenty-four anaesthetized open-chest dogs, nine of which were pretreated with reserpine. The following parameters were measured before, and at 15-min intervals following ligation for at least five hours : ECG, mean arterial blood pressure, aortic blood flow, left ventricular pressure, heart rate, peripheral resistance (P.R.), end-diastolic pressure, dP/dtmax, and "internal work" (I.W. = heart rate x dP/dtmax). It was found that aortic flow was similar in control and reserpine-pretreated dogs (753 +/- 43 vs. 744 +/- 57 ml/min respectively), even though heart rate, blood pressure and other parameters were significantly higher in the control animals. Furthermore, the controls could be divided into two groups : recoverers (R) and non-recoverers (N), on the basis of late stage haemodynamic differences. The ratio of PR/IW taken within one hour of ligation was significantly higher in the R group (496 +/- 69) and reserpine group (479 +/- 30) than in the N group (242 +/- 28), and could predict course of recovery in each dog studied. It is concluded that the presence of myocardial catecholamines may be deleterious to the ischemic heart when the PR or IW are disproportionately altered.


Pseudomonas aeruginosa AlgR Phosphorylation Status Differentially Regulates Pyocyanin and Pyoverdine Production.
Pseudomonas aeruginosa employs numerous, complex regulatory elements to control expression of its many virulence systems. The P. aeruginosa AlgZR two-component regulatory system controls the expression of several crucial virulence phenotypes. We recently determined, through transcriptomic profiling of a PAO1 ΔalgR mutant strain compared to wild-type PAO1, that algZR and hemCD are cotranscribed and show differential iron-dependent gene expression. Previous expression profiling was performed in strains without algR and revealed that AlgR acts as either an activator or repressor, depending on the gene. Thus, examination of P. aeruginosa gene expression from cells locked into different AlgR phosphorylation states reveals greater physiological relevance. Therefore, gene expression from strains carrying algR alleles encoding a phosphomimetic (AlgR D54E) or a phosphoablative (AlgR D54N) form were compared by microarray to PAO1. Transcriptome analyses of these strains revealed 25 differentially expressed genes associated with iron siderophore biosynthesis or heme acquisition or production. The PAO1 algR D54N mutant produced lower levels of pyoverdine but increased expression of the small RNAs prrf1 and prrf2 compared to PAO1. In contrast, the algR D54N mutant produced more pyocyanin than wild-type PAO1. On the other hand, the PAO1 algR D54E mutant produced higher levels of pyoverdine, likely due to increased expression of an iron-regulated gene encoding the sigma factor pvdS, but it had decreased pyocyanin production. AlgR specifically bound to the prrf2 and pvdS promoters in vitro AlgR-dependent pyoverdine production was additionally influenced by carbon source rather than the extracellular iron concentration per se AlgR phosphorylation effects were also examined in a Drosophila melanogaster feeding, murine acute pneumonia, and punch wound infection models. Abrogation of AlgR phosphorylation attenuated P. aeruginosa virulence in these infection models. These results show that the AlgR phosphorylation state can directly, as well as indirectly, modulate the expression of iron acquisition genes that may ultimately impact the ability of P. aeruginosa to establish and maintain an infection.IMPORTANCE Pyoverdine and pyocyanin production are well-known P. aeruginosa virulence factors that obtain extracellular iron from the environment and from host proteins in different manners. Here, we show that the AlgR phosphorylation state inversely controls pyoverdine and pyocyanin production and that this control is carbon source dependent. P. aeruginosa expressing AlgR D54N, mimicking the constitutively unphosphorylated state, produced more pyocyanin than cells expressing wild-type AlgR. In contrast, a strain expressing an AlgR phosphomimetic (AlgR D54E) produced higher levels of pyoverdine. Pyoverdine production was directly controlled through the prrf2 small regulatory RNA and the pyoverdine sigma factor, PvdS. Abrogating pyoverdine or pyocyanin gene expression has been shown to attenuate virulence in a variety of models. Moreover, the inability to phosphorylate AlgR attenuates virulence in three different models, a Drosophila melanogaster feeding model, a murine acute pneumonia model, and a wound infection model. Interestingly, AlgR-dependent pyoverdine production was responsive to carbon source, indicating that this regulation has additional complexities that merit further study.


Development and validation of an automated thawing and mixing workcell.
Working toward a goal of total laboratory automation, we are automating manual activities in our highest volume laboratory section. Because half of all specimens arriving in this laboratory section are frozen, we began by developing an automated workcell for thawing frozen specimens and mixing the thawed specimens to remove concentration gradients resulting from freezing and thawing. We developed an initial robotic workcell that removed specimens from the transport system's conveyor, blew high-velocity room temperature air at the tubes, mixed them, and replaced them on the conveyor. Aliquots of citrated plasma were frozen with thermocouples immersed in the tubes, and thawing times and temperatures were monitored. Completeness of mixing of thawed specimens was studied by careful removal of small aliquots from the uppermost layer of the upright tubes without disturbing tube contents and analysis of total protein and electrolytes. High velocity ambient air aimed directly at tubes ranging from 12 x 75 to 16 x 100 mm brought specimens to room temperature in a maximum of 23 min. Adequate mixing of the specimens by the workcell's robot required only 2 approximate 126 degrees movements from an upright starting point, a surprising observation, because laboratorians are usually trained to mix 10 or 20 times. We also observed that, in a frozen overfilled tube, resulting analyte concentrations will be lower because more concentrated solutes leak from the tube. A high-throughput, automated thawing and mixing workcell was successfully built, validated, and installed on our automated transport and sorting system.


Oral pharmacokinetically enhanced co-amoxiclav 2000/125 mg, twice daily, compared with co-amoxiclav 875/125 mg, three times daily, in the treatment of community-acquired pneumonia in European adults.
Pharmacokinetically enhanced co-amoxiclav 2000/125 mg was designed to achieve high serum concentrations of amoxicillin over the 12 h dosing interval to eradicate Streptococcus pneumoniae with amoxicillin MICs of at least 4 mg/L. This randomized, double-blind, double-dummy, multicentre study compared the efficacy and safety of oral co-amoxiclav 2000/125 mg twice daily versus co-amoxiclav 875/125 mg three times daily, for 7 or 10 days, in the treatment of community-acquired pneumonia (CAP). The per-protocol (PP) population at follow-up (Days 18-39) comprised 114 patients receiving co-amoxiclav 2000/125 mg and 116 receiving co-amoxiclav 875/125 mg. Clinical success at follow-up (primary efficacy endpoint) in the clinical PP population was 94.7% (108/114) for co-amoxiclav 2000/125 mg versus 88.8% (103/116) for co-amoxiclav 875/125 mg [treatment difference (TD) = 5.9%, 95% CI: 1.1, 13.0]. Bacteriological success in the bacteriology PP population at follow-up was 85.0% (17/20) for co-amoxiclav 2000/125 mg versus 77.3% (17/22) for co-amoxiclav 875/125 mg (TD = 7.7%, 95% CI: 15.8, 31.2). Penicillin-resistant S. pneumoniae (PRSP) were isolated in three patients (including two with bacteraemia) in the co-amoxiclav 2000/125 mg group (amoxicillin MICs 8 mg/L, penicillin MICs 4 mg/L) and one in the comparator group; all were clinical and bacteriological successes. Co-amoxiclav 2000/125 mg and co-amoxiclav 875/125 mg were associated with adverse events leading to withdrawal in 6.3% and 6.2% of patients, respectively. Co-amoxiclav 2000/125 mg twice daily was at least as effective clinically as co-amoxiclav 875/125 mg three times daily in the treatment of CAP. Although few patients in this study had PRSP infection, 3/3 were successfully treated with co-amoxiclav 2000/125 mg.