Implementation Issues of Virtual Desktop Infrastructure and Its Case Study for a Physician's Round at Seoul National University Bundang Hospital.
The cloud computing-based virtual desktop infrastructure (VDI) allows access to computing environments with no limitations in terms of time or place such that it can permit the rapid establishment of a mobile hospital environment. The objective of this study was to investigate the empirical issues to be considered when establishing a virtual mobile environment using VDI technology in a hospital setting and to examine the utility of the technology with an Apple iPad during a physician's rounds as a case study. Empirical implementation issues were derived from a 910-bed tertiary national university hospital that recently launched a VDI system. During the physicians' rounds, we surveyed patient satisfaction levels with the VDI-based mobile consultation service with the iPad and the relationship between these levels of satisfaction and hospital revisits, hospital recommendations, and the hospital brand image. Thirty-five inpatients (including their next-of-kin) and seven physicians participated in the survey. Implementation issues pertaining to the VDI system arose with regard to the highly availability system architecture, wireless network infrastructure, and screen resolution of the system. Other issues were related to privacy and security, mobile device management, and user education. When the system was used in rounds, patients and their next-of-kin expressed high satisfaction levels, and a positive relationship was noted as regards patients' decisions to revisit the hospital and whether the use of the VDI system improved the brand image of the hospital. Mobile hospital environments have the potential to benefit both physicians and patients. The issues related to the implementation of VDI system discussed here should be examined in advance for its successful adoption and implementation.


Inflammation and immune system contribution to the etiology of atherosclerosis: mechanisms and methods of assessment.
Immune system activation and inflammation are intricately involved in the development and progression of atherosclerosis. The purposes of this review are to (a) discuss effects of inflammation and the immune system across the lifespan of atherosclerotic plaque, (b) review current recommended testing techniques for assessing inflammation using blood and within the atherosclerotic plaque, and (c) link basic research in inflammation and immunology with ongoing clinical research with potential to impact prevention and treatment interventions in atherosclerotic disease. The atherosclerotic process is typically initiated in the presence of endothelial dysfunction by increased uptake, entrapment, and deposition of lipids, especially low-density lipoprotein (LDL). Once inside the intima, LDL can become oxidized (LDLox), which promotes further endothelial cell activation/injury, stimulates adhesion molecule expression, and releases chemotactic factors that promote leukocyte-endothelial interactions. The process of atherogenesis is highly regulated by the innate and adaptive immune systems and systemic inflammatory response. In addition, proinflammatory mediators play a key role in the lifespan of the atherosclerotic plaque and its vulnerability, favoring eventual plaque fissure when exposed to increasing hemodynamic stress. The complex atherosclerotic process involves the innate and adaptive immune systems and systemic inflammatory activation. Incorporation of advances in understanding inflammation and immune system contributions to the etiology of atherosclerosis into intervention research allows the development of novel approaches to prevention and treatment.


A mechanistic force model for simulating haptics of hand-held bone burring operations.
This paper presents a mechanistic model to predict the forces experienced during bone burring with application to haptic feedback for virtual reality surgical simulations. Bone burring is a hand-held operation where the force perceived by the surgeon depends on the cutting tool orientation and motion. The model of this study adapted the concept of specific cutting energy and material removal rate based on machining theory to calculate force distribution on the spherical tool surface in a three-dimensional setting. A design of experiments with three tool cutting angles and three feed motions was performed to calibrate and validate the model. Despite some variance in the results, model predictions showed similar trends to experimental force patterns. While the actual force profile also exhibits significant oscillation, the dominant frequencies of this oscillating force component were found to be independent of cutting and non-cutting instances, and hence could be imposed as a uniform background signal. Though the presented model is primarily applicable to abrasive burrs, it has far-reaching applications within other types of surgical simulations as well.


Novel Application of the Traditional Lipid Ratios as Strong Risk Predictors of NASH.
Limited data are available regarding the role of triglycerides, cholesterol and lipoproteins ratios as risk factors for nonalcoholic fatty liver disease (NAFLD) progression. In the present study, the investigators aimed to investigate the value of cardiovascular risk ratios of triglycerides, cholesterol, and lipoproteins as predictors of nonalcoholic steatohepatitis (NASH) and the correlation of such ratios with disease severity. This study included 131 overweight and obese patients with NAFLD who were divided into NASH, borderline NASH, and non-NASH fatty liver (NNFL) subgroups according to NAFLD activity score (NAS) in liver biopsy, and 60 healthy participants as a control group. Lipid profile and lipid ratios including triglycerides/HDL (TGs/HDL), low-density lipoprotein/high-density lipoprotein (LDL/HDL) and total cholesterol/HDL (TC/HDL) ratios were measured. Significantly higher triglycerides/HDL ratio was found in NASH and borderline NASH, while higher cholesterol/HDL ratio was found in borderline NASH in comparison to controls. There were positive correlations between TGs/HDL and steatosis, ballooning, inflammation, BMI, and NAS; between LDL/HDL and inflammation; and between cholesterol/HDL and BMI, steatosis, and NAS. The highest AUC was that of TG/HDL (0.744), at a cut-off point of 3, with 71.8% sensitivity and 76.8% specificity. Triglycerides, cholesterol and lipoprotein ratios showed higher levels in NASH and correlated with NAFLD severity, and above these cut-off ratios, we can rule in the NASH cases which confer also the cardiovascular morbidities. Structured lipid ratios could serve as markers to screen NASH progression from simple steatosis cases and clarify the link of NASH with the cardiovascular risk prediction in overweight and obese patients.


Electron density mapping of boron clusters via convolutional neural networks to augment structure prediction algorithms.
Determination and prediction of atomic cluster structures is an important endeavor in the field of nanoclusters and thereby in materials research. To a large extent the fundamental properties of a nanocluster are mainly governed by its molecular structure. Traditionally, structure elucidation is achieved using quantum mechanics (QM) based calculations that are usually tedious and time consuming for large nanoclusters. Various structural prediction algorithms have been reported in the literature (CALYPSO, USPEX). Although they tend to accelerate the structure exploration, they still require the aid of QM based calculations for structure evaluation. This makes the structure prediction process quite a computationally expensive affair. In this paper, we report on the creation of a convolutional neural network model, which can give relatively accurate energies for the ground state of nanoclusters from the promolecule density on the fly and could thereby be utilized for aiding structure prediction algorithms. We tested our model on dataset consisting of pure boron nanoclusters of varying sizes.


Sensitivity to global form in glass patterns after early visual deprivation in humans.
To compare the effects of early monocular versus early binocular deprivation on the perception of global form, we assessed sensitivity to global concentric structure in Glass patterns with varying ratios of paired signal dots to noise dots. Children who had been deprived by dense congenital cataracts in one (n=10) or both (n=8) eyes performed significantly worse than comparably aged children without eye problems. Consistent with previous results on sensitivity to global motion [Vision Research 42 (2002) 169], thresholds in the deprived eyes were significantly better after monocular deprivation than after binocular deprivation of comparable duration, even when there had been little patching of the nondeprived eye after monocular deprivation. Together, the results indicate that the competitive interactions between a deprived and nondeprived eye evident in the primary visual cortex can co-occur with complementary interactions in extrastriate cortex that enable a relative sparing of some visual functions after early monocular deprivation.


Fair Balance and Adequate Provision in Direct-to-Consumer Prescription Drug Online Banner Advertisements: A Content Analysis.
The current direct-to-consumer advertising (DTCA) guidelines were developed with print, television, and radio media in mind, and there are no specific guidelines for online banner advertisements. This study evaluates how well Internet banner ads comply with existing Food and Drug Administration (FDA) guidelines for DTCA in other media. A content analysis was performed of 68 banner advertisements. A coding sheet was developed based on (1) FDA guidance documents for consumer-directed prescription drug advertisements and (2) previous DTCA content analyses. Specifically, the presence of a brief summary detailing the drug's risks and side effects or of a "major statement" identifying the drug's major risks, and the number and type of provisions made available to consumers for comprehensive information about the drug were coded. In addition, the criterion of "fair balance," the FDA's requirement that prescription drug ads balance information relating to the drug's risks with information relating to its benefits, was measured by numbering the benefit and risk facts identified in the ads and by examining the presentation of risk and benefit information. Every ad in the sample included a brief summary of risk information and at least one form of adequate provision as required by the FDA for broadcast ads that do not give audiences a brief summary of a drug's risks. No ads included a major statement. There were approximately 7.18 risk facts for every benefit fact. Most of the risks (98.85%, 1292/1307) were presented in the scroll portion of the ad, whereas most of the benefits (66.5%, 121/182) were presented in the main part of the ad. Out of 1307 risk facts, 1292 were qualitative and 15 were quantitative. Out of 182 benefit facts, 181 were qualitative and 1 was quantitative. The majority of ads showed neutral images during the disclosure of benefit and risk facts. Only 9% (6/68) of the ads displayed positive images and none displayed negative images when presenting risks facts. When benefit facts were being presented, 7% (5/68) showed only positive images. No ads showed negative images when the benefit facts were being presented. In the face of ambiguous regulatory guidelines for online banner promotion, drug companies appear to make an attempt to adapt to regulatory guidelines designed for traditional media. However, banner ads use various techniques of presentation to present the advertised drug in the best possible light. The FDA should formalize requirements that drug companies provide a brief summary and include multiple forms of adequate provision in banner ads.


Effects of contact location and voltage amplitude on speech and movement in bilateral subthalamic nucleus deep brain stimulation.
Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in improving limb symptoms in Parkinson's disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN-DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off-stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1-minute monologue. Movement was assessed using the UPDRS-III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control.


Method for recovery of enteric viruses from estuarine sediments with chaotropic agents.
An evaluation was made of the ability of chaotropes, low-molecular-weight ionic compounds which enhance the solubilization of hydrophobic compounds in water, to improve the recovery of enteric viruses from highly organic estuarine sediments. Chaotropic agents alone were poor eluents of polioviruses from sediment but were effective when combined with 3% beef extract. Chaotropes of lower potency, NaNO3, NaCl, and KCl, were more efficient eluents than the stronger chaotropes, guanidium hydrochloride or sodium trichloroacetate. The most effective eluent was 2 M NaNO3 in 3% beef extract at pH 5.5, which eluted 71% of sediment-associated polioviruses. Efficient concentration of the sodium nitrate-beef extract eluate by organic flocculation required the addition of the antichaotrope (NH4)2SO4 to a 2 M concentration and Cat-Floc T (Calgon, Pittsburgh, Pa.) a cationic polyelectrolyte, to a 0.01% concentration. Dialysis of the final concentrate was necessary to reduce salts to nontoxic levels before assay in cell cultures. Trials with highly organic estuarine sediment seeded with high or low numbers of poliovirus 1, echovirus 1, or rotavirus SA-11 demonstrated the superiority of this method over two other methods currently in use.


Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of parkinsonism.
Evidence suggests that saffron and its major bioactives exhibit significant neuromodulatory effects in various animal models. However, specific data related to their efficacy to attenuate oxidative stress and neurotoxicity in animal models of Parkinson's disease (PD) are limited. Hence, we investigated the neuroprotective efficacy of saffron methanolic extract (SME) and its active constituent, crocin (CR) employing a Drosophila model of parkinsonism. We focussed on attenuation of Rotenone (ROT)-induced locomotor phenotype, oxidative stress, mitochondrial dysfunction and neurotoxicity in this model. SME and CR-enrichment significantly reduced ROT (500μM) induced mortality, rescued the locomotor phenotype and diminished the enhanced levels of oxidative stress markers in head/body regions of flies. The reduced levels of reduced glutathione (GSH) and total thiols (TSH) resulting from ROT exposure were significantly restored with concomitant enhancement of the antioxidant enzymes activities. Further, ROT-induced mitochondrial dysfunctions (MTT reduction, activities of SDH and NADH-Cyt C reductase (complexes I-III) enzymes) were markedly attenuated by SME/CR enrichment. While ROT elevated the activity of acetylcholinesterase (AChE) in head/body regions, both the treatments caused marked diminution of AChE activity and restored the dopamine levels suggesting their effectiveness to mitigate cholinergic function. Interestingly, SME/CR enrichment significantly delayed the onset of locomotor deficits and extended life span of flies among ROT (50μM)-stressed flies. In a satellite study, flies provided with SME/CR prophylaxis exhibited marked resistance to an acute Paraquat (PQ) challenge as evidenced by the lower incidence of lethality and improved locomotor phenotype. Taken together, the neuroprotective effects of saffron and crocin in the fly model may be largely attributable to its antioxidant action. Based on our findings, we propose that saffron may be exploited as a supplementary therapeutic agent in PD and other oxidative stress mediated neurodegenerative conditions.


Impact of the COVID-19 Pandemic on the General Mental Health in Sweden: No Observed Changes in the Dispensed Amount of Common Psychotropic Medications in the Region of Scania.
Some first investigations have focused on the consequences of the COVID-19 pandemic for the general mental health after its outbreak in 2020. According to multiple self-reporting surveys, symptoms of stress, anxiety, and depression have risen worldwide. Even some studies based on health care records start to be published, providing more objective and statistically reliable results. Additionally, concerns have been raised, to what extend the access to mental health care has been compromised by the COVID-19 outbreak. The aim of this study was to detect changes in prescription trends of common psychotropic medications in the Swedish region of Scania. The monthly dispensed amounts of selected pharmaceuticals were compared from January 2018 until January 2021, regarding the prescription trends before and after the outbreak of COVID-19. Using an interrupted time series analysis for each medication, no general trend changes were observed. On the one hand, a possible deterioration of the general mental health could not be confirmed by these results. On the other hand, the access to mental health care did not seem to be impaired by the pandemic. When interpreting findings related to the COVID-19 pandemic, regional differences and country-specific approaches for coping with the pandemic should be considered. The Swedish population, for instance, never experienced a full "lock-down" and within Sweden the time point of the outbreak waves differed regionally. In general, the effects of the COVID-19 outbreak on mental health are still unclear and need to be investigated further in an international comparison.


Inhibition and pH dependence of phosphite dehydrogenase.
Phosphite dehydrogenase (PTDH) catalyzes the NAD-dependent oxidation of phosphite to phosphate, a reaction that is 15 kcal/mol exergonic. The enzyme belongs to the family of D-hydroxy acid dehydrogenases. Five other family members that were analyzed do not catalyze the oxidation of phosphite, ruling out the possibility that this is a ubiquitous activity of these proteins. PTDH does not accept any alternative substrates such as thiophosphite, hydrated aldehydes, and methylphosphinate, and potential small nucleophiles such as hydroxylamine, fluoride, methanol, and trifluoromethanol do not compete with water in the displacement of the hydride from phosphite. The pH dependence of k(cat)/K(m,phosphite) is bell-shaped with a pK(a) of 6.8 for the acidic limb and a pK(a) of 7.8 for the basic limb. The pK(a) of 6.8 is assigned to the second deprotonation of phosphite. However, whether the dianionic form of phosphite is the true substrate is not clear since a reverse protonation mechanism is also consistent with the available data. Unlike k(cat)/K(m,phosphite), k(cat) and k(cat)/K(m,NAD) are pH-independent. Sulfite is a strong inhibitor of PTDH that is competitive with respect to phosphite and uncompetitive with respect to NAD(+). Incubation of the enzyme with NAD(+) and low concentrations of sulfite results in a covalent adduct between NAD(+) and sulfite in the active site of the enzyme that binds very tightly. Fluorescent titration studies provided the apparent dissociation constants for NAD(+), NADH, sulfite, and the sulfite-NAD(+) adduct. Substrate isotope effect studies with deuterium-labeled phosphite resulted in small normal isotope effects (1.4-2.1) on both k(cat) and k(cat)/K(m,phosphite) at pH 7.25 and 8.0. Solvent isotope effects (SIEs) on k(cat) are similar in size; however, the SIE of k(cat)/K(m,phosphite) at pH 7.25 is significantly larger (4.4), whereas at pH 8.0, it is the inverse (0.6). The pH-rate profile of k(cat)/K(m,phosphite), which predicts that the observed SIEs will have a significant thermodynamic origin, can account for these effects.


Music Interventions and Child Development: A Critical Review and Further Directions.
Research on the impact of music interventions has indicated positive effects on a variety of skills. These findings suggest musical interventions may have further potential to support educational processes and development of children. This paper reviews the latest evidence on the effect of musical interventions on the development of primary school-aged children. Four electronic databases were searched from January 2010 through June 2016 using music, music instruction, music education, music lesson, music training, development, child, student, and pupil as key words for the search. Two reviewers independently evaluated the studies to determine whether they met the stated inclusion criteria. Studies were compared on study setup, methodological quality, intervention components, outcome variables, and efficacy. A review of these selected studies (n = 46) suggestive beneficial effects of music intervention on development of children, although clear conclusions cannot be drawn. Possible influencing factors that might contribute to the outcome of intervention are reviewed and recommendations for further research are made.


Mitral periprosthetic leakage: contemporary results of surgical correction at a single centre.
Mitral periprosthetic leakage (PPL) is a serious complication following valve replacement. Conflicting outcomes of surgical treatment have been reported in the presence of multiple previous cardiac operations and associated co-pathological conditions. Sixty-five symptomatic patients (37 women, mean age 64.8 years) underwent conventional operations at our hospital from 2006 to 2015. Mitral PPL was the leading surgical indication, although associated procedures were included. Previous transcatheter procedures and leaks involving multiple prostheses were excluded. The median number of past mitral operations was 2 (range 1-5). PPL recurrence was observed in 29% of cases. A previous operation on the aortic or tricuspid valve was performed in 31 patients. Mitral PPL involved one-, two- or three-quarters of the mitral perimeter in 46, 43 and 11% of cases. Prosthetic refixation or replacement was performed in 24 and 41 patients, respectively. Annular reconstruction was necessary in 17% of prosthetic replacements. Associated procedures were performed in 19 patients. The operation was executed through a right minithoracotomy (unclamped aorta) in 20% of patients. In-hospital deaths occurred in 3.1%. After a median follow-up of 60 months, freedom from all-cause mortality was 96.8, 91.5 and 88.8% at 1, 3 and 5 years. Lateral leaks [P = 0.03; hazard ratio (HR) = 4.57, 95% confidence interval (CI): 1.13-18.3] and PPL relapse (P = 0.03; HR = 4.33, 95% CI: 1.12-16.7) were independently associated with death. At follow-up, 4 patients had a >2+ recurrent leak and 2 were reoperated. A customized conventional mitral reoperation still represents a satisfactory and effective treatment option for PPL and should be considered even in patients with very complex issues.


Methods of glioma sample processing for molecular diagnosis for the glioma tissue bank project.
Genome-wide sequencing in glioma samples provides comprehensive insights into oncogenesis and malignant transformation. Several distinct biomarkers have been proven to have clinical significance and are being widely applied in routine clinical practice. Standard sample processing lays the foundation for successful molecular testing. In this study, we found intraoperative neuronavigation ensured higher tumor purity during sample collection, and an automated device helped improve DNA quality and increased yields. These two technologies are beneficial for glioma tissue bank construction and provide for accurate molecular testing during routine clinical practice.


Age of first exposure to football and later-life cognitive impairment in former NFL players.
To determine the relationship between exposure to repeated head impacts through tackle football prior to age 12, during a key period of brain development, and later-life executive function, memory, and estimated verbal IQ. Forty-two former National Football League (NFL) players ages 40-69 from the Diagnosing and Evaluating Traumatic Encephalopathy using Clinical Tests (DETECT) study were matched by age and divided into 2 groups based on their age of first exposure (AFE) to tackle football: AFE <12 and AFE ≥12. Participants completed the Wisconsin Card Sort Test (WCST), Neuropsychological Assessment Battery List Learning test (NAB-LL), and Wide Range Achievement Test, 4th edition (WRAT-4) Reading subtest as part of a larger neuropsychological testing battery. Former NFL players in the AFE <12 group performed significantly worse than the AFE ≥12 group on all measures of the WCST, NAB-LL, and WRAT-4 Reading tests after controlling for total number of years of football played and age at the time of evaluation, indicating executive dysfunction, memory impairment, and lower estimated verbal IQ. There is an association between participation in tackle football prior to age 12 and greater later-life cognitive impairment measured using objective neuropsychological tests. These findings suggest that incurring repeated head impacts during a critical neurodevelopmental period may increase the risk of later-life cognitive impairment. If replicated with larger samples and longitudinal designs, these findings may have implications for safety recommendations for youth sports.


Assisted injection provider practices and motivations in Los Angeles and San Francisco California 2016-18.
Assisted injection is a high-risk and common practice among people who inject drugs (PWID) and occurs for diverse reasons according to qualitative research. To develop interventions for reducing assisted injection risks, it is important to understand the practices of PWID who provide injection assistance, including their motivations for providing assistance. Using follow-up data from an efficacy trial among PWID recruited in Los Angeles and San Francisco, CA (n=601), we present descriptive statistics on motivations for providing injection assistance and use multivariable logistic regression modelling to examine factors associated with these motivations. PWID provided injection assistance most commonly to friends and acquaintances. A quarter provided assistance on a daily basis. The most common motivations for providing assistance were skill and injury prevention. PWID also provided assistance to stop pestering and for compensation in money or drugs. In separate models examining factors associated with the five main motivations, we found injury prevention to be associated with skill injecting others, neck injection, methamphetamine use, and recycling income. Pestering was associated with injury prevention, neck and hand injection, speedball use, and syringe selling. Skill was associated with injury prevention, neck and hand injection, being physically assaulted, and age. Providing assistance for money was associated with providing assistance for food or drugs, armpit injections, being female, and providing assistance more frequently. Providing assistance for drugs was associated with compensation in food or money, goofball injection, selling drugs, and panhandling. Providing injection assistance is associated with injection needs of recipients and drug scene participation. We urgently need new interventions for reducing assisted injection risks. Since injection providers report being motivated by skill and to prevent injury, interventions such as training in safer injection techniques are likely to be met with enthusiasm.


High frequency of recessive WFS1 mutations among Indian children with islet antibody-negative type 1 diabetes.
While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology is not studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. We conducted a multicentre, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2 and zinc transporter 8, using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous, and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8 and PTF1A loci were detected. Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.


[The state of the atmosphere and bronchial hypersensitivity].
A bronchial provocative test employing acetylcholine revealed an excess in the numbers of the hypersensitive persons living under ecologic health hazard conditions, of 3,5-fold, which fact permits recommending it to be used in population studies to identify and administer prophylaxis of obstructive lung diseases in a timely fashion. Hypersensitivity of the bronchi in those people living under ecologic health hazard conditions is accompanied by an activation of peroxidation processes as well as changes in the parameters associated with the immune response.


On community leadership: stories about collaboration in action research.
This article provides an account of a 10-year collaborative documentation of community leadership in an African American community on the South side of Chicago. The stories are oriented to several critical incidents in the life course of the collaboration. They are told from the perspectives of one university professor, four graduate students, and one community leader. Together they provide an account of how this research was shaped by the interactions of the research team with members of the community, how research questions emerged, methodologies were developed, ways of gathering data were tried and tested, and interpretations of data unfolded. Special attention is given to the ways in which the process and products of this research contributed to the community's own process of leadership development. The stories also discuss the various roles participants in this collaboration played both in the academic arena and in the community, and how they experienced gender, race, nationality, and social status.


Assessment of tear film in subjects with a high body mass index.
The aim of the study was to assess the tear film in subjects with a high body mass index (BMI). Twenty male subjects aged 23-42 years (mean ± standard deviation =31.3±5.7 years) with a high BMI [median (interquartile range) =31.8 (5.2) kg/m2] were recruited. An age-matched control group of twenty male subjects aged 22-38 years with a normal BMI [20.5 (2.8) kg/m2] also participated in the study. There were significant (Kolmogorov-Smirnov test; P<0.05) differences in the BMI, non-invasive tear break-up time (NITBUT), and tear ferning (TF) scores between the study and control groups. There were some differences in the ocular surface disease index (OSDI), tear meniscus height (TMH), and phenol red thread (PRT) scores between the study and control groups, but these differences were not significant (Kolmogorov-Smirnov test; P>0.05). For the study group, the NITBUT and TF tests mean scores showed a dry eye condition (8.5±2.8 s and 2.0±1.1, respectively). However, these two tests showed a normal eye condition within the control group (14.7±2.8 s and 0.7±0.6, respectively). The TMH score had strong correlations with the NITBUT (r=0.711; P=0.001) and PRT scores (r=0.566; P=0.009) and strong negative correlations with age (r=-0.503; P=0.024) and the OSDI scores (r=-0.520; P=0.018). The TF score had a strong correlation with age (r=0.579; P=0.007) and strong negtive correlations with the scores from the NITBUT (r=-0.525; P=0.018), TMH (r=-0.575; P=0.008), and PRT (r=-0.773; P=0.001) tests. The acquired data suggest a high BMI has an effect on the quality of tears. The quality of tears seems to be lower in subjects with a high BMI compared with normal subjects. On the other hand, the tear volume in subjects with a high BMI was just as high and adequate as for normal eye subjects.


CRISPRpred: A flexible and efficient tool for sgRNAs on-target activity prediction in CRISPR/Cas9 systems.
The CRISPR/Cas9-sgRNA system has recently become a popular tool for genome editing and a very hot topic in the field of medical research. In this system, Cas9 protein is directed to a desired location for gene engineering and cleaves target DNA sequence which is complementary to a 20-nucleotide guide sequence found within the sgRNA. A lot of experimental efforts, ranging from in vivo selection to in silico modeling, have been made for efficient designing of sgRNAs in CRISPR/Cas9 system. In this article, we present a novel tool, called CRISPRpred, for efficient in silico prediction of sgRNAs on-target activity which is based on the applications of Support Vector Machine (SVM) model. To conduct experiments, we have used a benchmark dataset of 17 genes and 5310 guide sequences where there are only 20% true values. CRISPRpred achieves Area Under Receiver Operating Characteristics Curve (AUROC-Curve), Area Under Precision Recall Curve (AUPR-Curve) and maximum Matthews Correlation Coefficient (MCC) as 0.85, 0.56 and 0.48, respectively. Our tool shows approximately 5% improvement in AUPR-Curve and after analyzing all evaluation metrics, we find that CRISPRpred is better than the current state-of-the-art. CRISPRpred is enough flexible to extract relevant features and use them in a learning algorithm. The source code of our entire software with relevant dataset can be found in the following link: https://github.com/khaled-buet/CRISPRpred.


Oyster parasites Bonamia ostreae and B. exitiosa co-occur in Galicia (NW Spain): spatial distribution and infection dynamics.
Bonamiosis constrains the flat oyster industry worldwide. The protistan species Bonamia ostreae had been considered solely responsible for this disease in Europe, but the report of B. exitiosa infecting Ostrea edulis 5 yr ago in Galicia (NW Spain), and subsequently in other European countries, raised the question of the relevance of each species in bonamiosis. The spatial distribution of B. exitiosa and B. ostreae in Galicia was addressed by sampling 7 natural O. edulis beds and 3 culture raft areas, up to 3 times in the period 2009 to 2010. B. ostreae infected flat oysters in every natural bed and every raft culture area. True B. exitiosa infections (histological diagnosis) were detected in every raft culture area but only in 2 natural beds, i.e. in 4 rías. PCR-positive results for B. exitiosa were recorded in 4 out of 5 beds where true infections were not found, thus the occurrence of B. exitiosa in those 4 beds cannot be ruled out. Additionally, 4 cohorts of hatchery-produced oyster spat were transferred to a raft to analyse Bonamia spp. infection dynamics through oyster on-growing. The highest percentages of oysters PCR-positive for both Bonamia spp. were recorded in the first months of on-growing; other peaks of PCR-positive diagnosis were successively lower. Differences in the percentage of PCR-positive cases and in the prevalence of true infection between B. exitiosa and B. ostreae through on-growing were not significant. Our results support that B. exitiosa is adapted to infect O. edulis in the Galician marine ecosystem.


HMGA1 drives metabolic reprogramming of intestinal epithelium during hyperproliferation, polyposis, and colorectal carcinogenesis.
Although significant progress has been made in the diagnosis and treatment of colorectal cancer (CRC), it remains a leading cause of cancer death worldwide. Early identification and removal of polyps that may progress to overt CRC is the cornerstone of CRC prevention. Expression of the High Mobility Group A1 (HMGA1) gene is significantly elevated in CRCs as compared with adjacent, nonmalignant tissues. We investigated metabolic aberrations induced by HMGA1 overexpression in small intestinal and colonic epithelium using traveling wave ion mobility mass spectrometry (TWIMMS) in a transgenic model in which murine Hmga1 was misexpressed in colonic epithelium. To determine if these Hmga1-induced metabolic alterations in mice were relevant to human colorectal carcinogenesis, we also investigated tumors from patients with CRC and matched, adjacent, nonmalignant tissues. Multivariate statistical methods and manual comparisons were used to identify metabolites specific to Hmga1 and CRC. Statistical modeling of data revealed distinct metabolic patterns in Hmga1 transgenics and human CRC samples as compared with the control tissues. We discovered that 13 metabolites were specific for Hmga1 in murine intestinal epithelium and also found in human CRC. Several of these metabolites function in fatty acid metabolism and membrane composition. Although further validation is needed, our results suggest that high levels of HMGA1 protein drive metabolic alterations that contribute to CRC pathogenesis through fatty acid synthesis. These metabolites could serve as potential biomarkers or therapeutic targets.


[Psychoanalytic Treatments without Medication and Behavioral Therapy Treatments with and without Medication in Children with the Diagnosis of ADHD and/or Conduct Disorder].
The controlled, prospective intervention study without randomization with a non-inferiority study design investigates the effectiveness of psychoanalytic treatments without medication in comparison to behavioral therapy treatments with and without medication in children aged 6 to 11 years with a diagnosis of ADHD and/or conduct disorder. 73 children (58 boys and 15 girls) were included in the study. Diagnostics before treatment, at end of treatment and at follow-up after 38 months included a standardized clinical interview (DISYPS-KJ), questionnaires for parents, teachers and children (DISYPS-KJ, CBCL, TRF, CPRS, CTRS, ILK), intelligence test and behavioral observation of the child. Primary outcome criterion was disorder-specific symptom reduction at end of treatment and follow-up. Both treatment groups showed significant symptom reductions at end of treatment and at follow-up. There were no significant differences between treatment groups. Parent and teacher ratings showed significant improvements in both groups at end of treatment and at follow-up on the ADHD index, oppositional behavior, and hyperactivity/impulsivity scales, as well as on the externalizing and internalizing behavior problems scales. Quality of life improved for children in both treatment groups.


[Effect of Long-Term Biochar Application on Soil Respiration in Flue-Cured Tobacco Planting Fields in Henan Province].
A five year (2013-2017) experiment was conducted to explore the effects of biochar application on the dynamic changes in soil respiration, soil water, and heat factors under four treatments:CK (without biochar), T1 (with 1.5 t·hm-2biochar), T2 (with 15 t·hm-2biochar), and T3 (with 45 t·hm-2biochar). The results showed that:① the soil respiration rate in the growing season of flue-cured tobacco was significantly reduced by 25.89% under the five year application of medium-dose biochar (T2:15 t·hm-2) in soil, while it was significantly increased by 21.48% when the applied dose increased to 45 t·hm-2(T3) (P<0.05). ② The long-term application of medium-dose biochar in the soil significantly reduced the soil heterotrophic respiration and autotrophic respiration rates by 29.80% and 28.75%, respectively. Meanwhile, the application of high-dose biochar (T3:45 t·hm-2) significantly increased the heterotrophic respiration rate by 28.88%. In addition, the application of low-dose biochar (T1:1.5 t·hm-2) and medium-dose biochar significantly increased the proportion of autotrophic respiration, whereas the high-dose biochar application significantly increased the proportion of heterotrophic respiration (P<0.05). ③ The addition of low-dose biochar to the soil significantly reduced the soil temperature at 5 cm in the growing season of flue-cured tobacco, while the high-dose application significantly reduced the soil humidity. There was a significant index correlation between soil respiration and soil temperature at 5 cm but no significant correlation with soil humidity at 5 cm (P<0.05). Ultimately, the application of low-dose biochar for five years in soil had no effect on soil respiration, and the application of the proper amount of biochar had a carbon sequestration effect. Additionally, large-dose biochar application may be counterproductive. It is recommended that the application range of biochar should be controlled within 15 t·hm-2.


SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome.
Acetylation is increasingly recognized as an important metabolic regulatory posttranslational protein modification, yet the metabolic consequence of mitochondrial protein hyperacetylation is unknown. We find that high-fat diet (HFD) feeding induces hepatic mitochondrial protein hyperacetylation in mice and downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice. The lipogenic enzyme stearoyl-CoA desaturase 1 is highly induced in SIRT3KO mice, and its deletion rescues both WT and SIRT3KO mice from HFD-induced hepatic steatosis and insulin resistance. We further identify a single nucleotide polymorphism in the human SIRT3 gene that is suggestive of a genetic association with the metabolic syndrome. This polymorphism encodes a point mutation in the SIRT3 protein, which reduces its overall enzymatic efficiency. Our findings show that loss of SIRT3 and dysregulation of mitochondrial protein acetylation contribute to the metabolic syndrome.


[Characteristics of the pKMR plasmids found in Shigella flexneri].
The clinical isolate of Sh. flexneri 1b, resistant to 5 antibiotics and sulfonamides, has been studied by the method of conjugation and found to have a group of transfer-suppressed pKMR-plasmids: pKMR 204-1 (Ap Sm Tc Cm Km Su), pKMR 204-2 (Sm Km Su), pKMR 204-5 (Km Su) and pKMR 204-7 (Sm Tc Cm Km Su), whose molecular weight was 99, 71.2, 73.8 and 59.5 Md respectively. The treatment of the plasmids with restriction endonuclease BamHI has revealed that plasmids pKMR 204-2 and pKMR 204-5 are definitely related to plasmid KMR 204-1, being its deletion mutants. At the same time plasmids pKMR 204-1 and pKMR 204-7 differ in their sensitivity to endonuclease BamHI and stably coexist within the same cell, thus seeming to belong to different compatibility groups.


Chronic kidney disease and the risk of stroke: a systematic review and meta-analysis.
People with chronic kidney disease (CKD) have an increased risk of stroke but the magnitude of increased risk and the independent effects of glomerular filtration rate (GFR) and albuminuria are unclear. We aimed to quantify the association between the independent and combined effects of GFR and albuminuria on stroke risk. We searched MEDLINE and EMBASE (February 2014) for cohort studies or randomized controlled trials (RCTs) which reported stroke incidence in adults with a baseline measurement of GFR and/or albuminuria. We extracted study and participant characteristics, risk of bias and relative risks (RR, with confidence interval; CI) of stroke associated with GFR and/or quantity of albuminuria, synthesized data using random effects meta-analysis and explored heterogeneity using meta-regression. We identified 83 studies; 63 cohort studies (2 085 225 participants) and 20 RCTs (168 516 participants) reporting 30 392 strokes. There was an inverse linear relationship between GFR and risk of stroke, with risk of stroke increasing 7% (RR: 1.07, CI: 1.04-1.09) for every 10 mL/min/1.73 m(2) decrease in GFR. A 25 mg/mmol increase in albumin-creatinine ratio was associated with a 10% increased risk of stroke (RR: 1.10, 95% CI: 1.01-1.20). The effect of albuminuria was independent of GFR. Results were not different across subtypes of stroke, sex and varying prevalence of cardiovascular risk factors. Stroke risk increases linearly and additively with declining GFR and increasing albuminuria. CKD staging may also be a useful clinical tool for identifying people who may benefit most from interventions to reduce cardiovascular risk.


Pushing proficiency testing results to their limits.
PT is a valuable component of laboratory quality control and management practice. PT results are useful to determine over time that a method is performing in a laboratory according to the manufacturer's design parameters, as exhibited by the performance characteristic of a large group of peer laboratories. PT peer group results give a good measure of the interlaboratory imprecision of a method, and summary reports document the state-of-the-art in user preference. PT results typically cannot be used to validate the accuracy of a method or its clinical utility or to compare the accuracy of various methods. These limitations are caused by the common and unpredictable matrix interferences with PT materials and most routine laboratory methods. In situations where a laboratory adjusts the calibration of one method to make patient results agree with those of another method, PT specimens results must be reported without calibration adjustments to allow those results to be compared to an appropriate peer group mean target value.


Structure and subcellular localization of a small RNA-binding protein from tobacco.
In this study, a cDNA encoding a small RNA-binding protein was isolated from a Nicotiana sylvestris cDNA library. The predicted protein (RGP-3) is 144 amino acid residues long, and contains a consensus sequence-type RNA binding domain (CS-RBD) of 83 amino acids and a short glycine-rich region of 15 amino acids. RGP-3 synthesized in Escherichia coli has high affinity for poly(U). Immunocytochemical analysis indicated that RGP-3 is localized in the nucleoplasm, and that RGP-1b, a related protein reported previously, is localized in the nucleolus. Possible roles of these proteins in pre-mRNA or pre-rRNA processing are discussed.


History of weight control attempts among adolescent girls with loss of control eating.
Loss of control (LOC) eating and a weight control attempt (WCA) history during adolescence are important behavioral risk factors for eating disorders and obesity. The current study investigated the significance of the presence of a WCA history among adolescent girls with LOC eating. Participants were 114 obesity-prevention-seeking 12-17-year-old (M = 14.5, SD = 1.7 years) girls who were between the 75th and 97th body mass index (BMI) percentile (BMI-z: M = 1.5, SD = 0.3) and reported LOC eating episodes during the previous month (M = 4.0, SD = 4.9 episodes; Median = 2.0). Measures included the Eating Disorder Examination to assess LOC eating, eating pathology, and WCA history, and self-report questionnaires for symptoms of general psychopathology. Eating behavior was observed during a laboratory meal designed to capture a LOC eating episode. 67.5% reported a WCA history. As compared to girls without a WCA history (no-WCA), those with a WCA history (WCA) had greater disordered eating attitudes and depressive symptoms (ps < .04). There were no significant group differences in BMI-z or LOC eating frequency (ps > .10). During the laboratory meal, WCA consumed less energy from snack-type foods than no-WCA (M = 245.0, SD = 156.1 vs. M = 341.6, SD = 192.3 kcal; p = .01). Reported WCAs are highly prevalent and are associated with greater psychopathology symptoms among adolescent girls with LOC eating. Prospective data are needed to determine whether these overlapping risk behaviors confer differential vulnerability for developing eating disorders and obesity.


Knowledge of diabetes among patients in the United Arab Emirates and trends since 2001: a study using the Michigan Diabetes Knowledge Test.
Knowledge of diabetes among patients with the disease in the United Arab Emirates is essential for effective self-management. We assessed the level of diabetes-related knowledge among patients and compared it with that found in previous studies in the same city. A cross-sectional study, using an interviewer-administered questionnaire, was conducted at two clinics in Al Ain, United Arab Emirates. The Michigan Diabetes Knowledge Test, translated into Arabic, was used to assess knowledge of diabetes. Of 165 participants with diabetes, 130 (78.8%) were women. The mean knowledge score was low at 55% (6.6 out of a maximum possible score of 12, standard deviation 1.8). This is comparable to levels found in previous studies: 55.5% in 2001 and 68.2% in 2006. Misconceptions about the diabetic diet and blood testing were common. The level of diabetes-related knowledge has remained low since 2001. These results are of concern in view of the substantial investments made in diabetes care and health education in the region.


The relationship of adult morphology and early social signalling of the domestic dog (Canis familiaris).
Most research on dog communication has focused on either the use of lupine signals during intra-specific interactions or has studied single-breed groups, with little regard to the effects of morphological change in the dog on their communication. This oversight ignores the fact that most modern dog breeds do not resemble the wolf and thus they have lost the ability to send some signals and may encounter communication problems. Using puppies in 40 litters from 32 breeds, we investigated the relationship between the frequencies of behaviours (social signals), and the adult morphology of these dogs. Despite a high level of precision, no statistically significant relationships were found between the deviation of the adult morphology from the ancestral lupine morphotype and early social signalling in the dog. We concluded that any communication loss due to morphological deviation, is not compensated for by increasing the frequency of signalling behaviours at this age.


Humanitarian information systems and emergencies in the Greater Horn of Africa: logical components and logical linkages.
Natural and man-made emergencies are regular occurrences in the Greater Horn of Africa region. The underlying impoverishment of whole populations is increasing, making it more difficult to distinguish between humanitarian crises triggered by shocks and those resulting from chronic poverty. Shocks and hazards can no longer be seen as one-off events that trigger a one-time response. In countries that are both poor and exposed to frequent episodes of debilitating drought or chronic conflict, information needs tend to be different from the straightforward early warning/commodity accounting models of information systems that have proven reliable in past emergencies. This paper describes the interdependent components of a humanitarian information system appropriate for this kind of complex environment, noting the analytical links between the components and operational links to programme and policy. By examining a series of case studies from the Greater Horn region, the paper demonstrates that systems lacking one or more of these components will fail to provide adequate information--and thus incur humanitarian costs. While information always comes with a cost, the price of poor information--or none--is higher. And in situations of chronic vulnerability, in which development interventions are likely to be interspersed with both safety nets and emergency interventions on a recurrent basis, investment in improved information is a good investment from both a humanitarian and a financial viewpoint.


[Accuracy of renal volume assessment in children by three-dimensional sonography].
Prospective evaluation of the accuracy of three-dimensional ultrasound (3DUS) to assess the renal parenchymal volume. CT, MRI, 2DUS and 3DUS were used to measure the renal volume in 40 patients (range: neonate to 17 years; mean age: 8.95 years). The 3DUS was determined with a Voluson 730 (Kretztechnik, GE) or an external 3D-system (EchoTech, GE) using electromagnetic positioning sensors attached to conventional 2DUS-equipment. The 2DUS volume was calculated with the ellipsoid equation and the 3DUS volume computed with the system integrated software. For CT and MRI, planimetric analysis was used to determine the renal parenchymal volume, whereby the dilated collecting system of a hydronephrosis was subtracted to obtain the real renal parenchymal volume. The results of 2DUS and 3DUS were compared to the results of CT and MRI, and inter- and intraobserver variabilities were calculated. In 74 of 77 kidneys, the 3DUS study was of diagnostic quality. The accuracy of the 3DUS volumes compared well to the CT and MRI volumes with a mean difference of -1.8 +/- 4.6 % versus a mean difference of -2.4 +/- 15.4 % for 2DUS. In normal kidneys, the accuracy was -2.6 +/- 4.4 % for 3DUS and -3.8 +/- 14.7 % for 2DUS. In hydronephrosis, the accuracy was +4.0 +/- 5.9 % and +9.6 +/- 21.3 %, respectively, indicating that 3DUS is more accurate than 2DUS, particularly in kidneys with a dilated collecting system. Inter- and intraobserver variabilities were +/- 7.3 % and +/- 5.3 %. For assessing the renal parenchymal volume in children, 3DUS is feasible and comparable to CT and MRI.


Recent advances in β-galactosidase and fructosyltransferase immobilization technology.
The highly demanding conditions of industrial processes may lower the stability and affect the activity of enzymes used as biocatalysts. Enzyme immobilization emerged as an approach to promote stabilization and easy removal of enzymes for their reusability. The aim of this review is to go through the principal immobilization strategies addressed to achieve optimal industrial processes with special care on those reported for two types of enzymes: β-galactosidases and fructosyltransferases. The main methods used to immobilize these two enzymes are adsorption, entrapment, covalent coupling and cross-linking or aggregation (no support is used), all of them having pros and cons. Regarding the support, it should be cost-effective, assure the reusability and an easy recovery of the enzyme, increasing its stability and durability. The discussion provided showed that the type of enzyme, its origin, its purity, together with the type of immobilization method and the support will affect the performance during the enzymatic synthesis. Enzymes' immobilization involves interdisciplinary knowledge including enzymology, nanotechnology, molecular dynamics, cellular physiology and process design. The increasing availability of facilities has opened a variety of possibilities to define strategies to optimize the activity and re-usability of β-galactosidases and fructosyltransferases, but there is still great place for innovative developments.


Is there any correlation between the total number of neutrophils in plasma and concentration of interleukin-8 in psoriatic patients?
Interleukin-8 is a chemotactic agent for neutrophils which causes their simultaneous activation. This cytokine of the chemokines family contributes considerably to the processes observed in the psoriatic epidermis with the participation of neutrophils. The level of IL-8 in plasma of psoriatic patients during the period of acute and chronic relapses, the number of neutrophils in blood, and the correlation between these parameters were analysed. The study included 55 patients affected by psoriasis (psoriasis severity and activity index ranging from 16.20 to 70.20) and 10 people of the control group. Psoriatic patients were divided into two groups: 'acute psoriasis'--with an acute relapse of the disease (up to one month)--15 patients, and 'chronic psoriasis'--with a longer period of relapse--40 patients. IL-8 plasma levels were determined with the use of the ELISA method. The total number of neutrophils was assessed in blood and smears, and calculations were performed. The results of the study showed higher levels of IL-8 in the plasma of patients with acute psoriasis, however, an elevated number of neutrophils in this group was not statistically significant.


Improved Nocturnal Glycaemia and Reduced Insulin Use Following Clinical Exercise Trial Participation in Individuals With Type 1 Diabetes.
Aim: To explore the influence of clinical exercise trial participation on glycaemia and insulin therapy use in adults with type 1 diabetes (T1D). Research Design and Methods: This study involved a secondary analysis of data collected from 16 individuals with T1D who completed a randomized clinical trial consisting of 23-h in-patient phases with a 45-min evening bout of moderate intensity continuous exercise. Participants were switched from their usual basal-bolus therapy to ultra-long acting insulin degludec and rapid-acting insulin aspart as well as provided with unblinded interstitial flash-glucose monitoring systems. To assess the impact of clinical trial participation, weekly data obtained at the screening visit (pre-study involvement) were compared against those collated on the last experimental visit (post-study involvement). Interstitial glucose [iG] data were split into distinct glycaemic ranges and stratified into day (06:00-23:59) and night (00:00-05:59) time periods. A p-value of ≤ 0.05 was accepted for significance. Results: Following study completion, there were significant decreases in both the mean nocturnal iG concentration (Δ-0.9 ± 4.5 mmol.L-1, p < 0.001) and the time spent in severe hyperglycaemia (Δ-7.2 ± 9.8%, p = 0.028) during the night-time period. The total daily (Δ-7.3 ± 8.4 IU, p = 0.003) and basal only (Δ-2.3 ± 3.8 IU, p = 0.033) insulin dose requirements were reduced over the course of study involvement. Conclusions: Participation in clinical research may foster improved nocturnal glycaemia and reduced insulin therapy use in people with T1D. Recognition of these outcomes may help encourage volunteers to partake in clinical research opportunities for improved diabetes-related health outcomes. Clinical Trial Registration: DRKS.de; DRKS00013509.


Indirect genetic effects contribute substantially to heritable variation in aggression-related traits in group-housed mink (Neovison vison).
Since the recommendations on group housing of mink (Neovison vison) were adopted by the Council of Europe in 1999, it has become common in mink production in Europe. Group housing is advantageous from a production perspective, but can lead to aggression between animals and thus raises a welfare issue. Bite marks on the animals are an indicator of this aggressive behaviour and thus selection against frequency of bite marks should reduce aggression and improve animal welfare. Bite marks on one individual reflect the aggression of its group members, which means that the number of bite marks carried by one individual depends on the behaviour of other individuals and that it may have a genetic basis. Thus, for a successful breeding strategy it could be crucial to consider both direct (DGE) and indirect (IGE) genetic effects on this trait. However, to date no study has investigated the genetic basis of bite marks in mink. A model that included DGE and IGE fitted the data significantly better than a model with DGE only, and IGE contributed a substantial proportion of the heritable variation available for response to selection. In the model with IGE, the total heritable variation expressed as the proportion of phenotypic variance (T2) was six times greater than classical heritability (h2). For instance, for total bite marks, T2 was equal to 0.61, while h2 was equal to 0.10. The genetic correlation between direct and indirect effects ranged from 0.55 for neck bite marks to 0.99 for tail bite marks. This positive correlation suggests that mink have a tendency to fight in a reciprocal way (giving and receiving bites) and thus, a genotype that confers a tendency to bite other individuals can also cause its bearer to receive more bites. Both direct and indirect genetic effects contribute to variation in number of bite marks in group-housed mink. Thus, a genetic selection design that includes both direct genetic and indirect genetic effects could reduce the frequency of bite marks and probably aggression behaviour in group-housed mink.


The pharmacokinetics of ziprasidone in subjects with normal and impaired hepatic function.
To assess whether hepatic impairment influences the pharmacokinetics of ziprasidone. Thirty subjects with normal hepatic function or a primary diagnosis of clinically significant cirrhosis (Child-Pugh A or B) were enrolled into an open-label, multicentre, multiple-dose study. The subjects with chronic, stable hepatic impairment and the matched control subjects received ziprasidone 40 mg day(-1), given orally with food, as two divided daily doses for 4 days and a single 20 mg dose on the morning of day 5. Pharmacokinetic variables were determined from multiple venous blood samples collected on days 1 and 5. Liver function was evaluated quantitatively using antipyrine. On day 1 there were no statistically significant differences in the pharmacokinetics (AUC(0,12 h), Cmax, tmax) of ziprasidone between the two groups. On day 5 there were no statistically significant differences in the Cmax or tmax for ziprasidone between the two groups. The mean AUC(0,12 h) for ziprasidone was statistically significantly greater in the hepatically impaired subjects compared with the normal subjects (590 ng ml(-1) h vs. 467 ng ml(-1) h, P = 0. 042). However, the AUC(0,12 h) increased by only 26% in the cirrhotic group compared with the matched control group. The ziprasidone lambda(z) in the subjects with normal hepatic function was statistically significantly greater than that in the hepatically impaired subjects (P<0.001). There was no correlation between antipyrine lambda(z) and ziprasidone lambda(z) in the subjects with normal hepatic function or in those with hepatic impairment. The findings of this study indicate that mild to moderate hepatic impairment does not result in clinically significant alteration of ziprasidone pharmacokinetics.


TETRASPANINs in Plants.
Tetraspanins are small transmembrane proteins that laterally associate with each other and cluster with numerous partner proteins as well as lipids. These interactions result in the formation of a distinct class of membrane domains, the tetraspanin-enriched microdomains (TEMs), which influence numerous cellular processes such as cell adhesion and fusion, intracellular membrane trafficking, signaling, morphogenesis, motility as well as interaction with pathogens and cancer development. The majority of information available about tetraspanins is based on studies using animal models or cell lines, but tetraspanins are also present in fungi and plants. Recent studies indicate that tetraspanins have important functions in plant development, reproduction and stress responses. Here we provide a brief summary of the current state of tetraspanin research in plants.


Determining the Minimal Clinically Important Difference for 6-Minute Walk Distance in Fibromyalgia.
The aim of this study was to estimate the minimal clinically important difference (MCID) for 6-min walk distance (6MWD) in patients with fibromyalgia. Data from a recently completed trial that included 187 patients who completed the 6-min walk test, Fibromyalgia Impact Questionnaire (FIQ), and Short-Form 36 (SF36) at 12 and 36 wks were used to examine longitudinal changes in 6MWD. An anchor-based approach that used linear regression analyses was used to determine the MCID for 6MWD, using the total FIQ score (FIQ-Total) and SF36-physical function domain as clinical anchors. The mean (SD) change in 6MWD from baseline to week 36 was 34.4 (65.2) m (P < 0.001). The anchor-based MCIDs for the 6MWD were 156 and 167 m for the FIQ and SF36-physical function domain, respectively. These MCIDs correspond with clinically meaningful improvements in FIQ (14% reduction) and SF36-physical function domain (10-point increase). The MCID for 6MWD in patients with fibromyalgia was 156 to 167 m. These findings provide the first evidence of the change in 6MWD that is perceived by patients to be clinically meaningful. Further research using other MCID calculation methods is needed to refine estimates of the MCID for 6MWD in patients with fibromyalgia.


Applications of Noble Metal-Based Nanoparticles in Medicine.
Nanoparticles have unique, size-dependent properties, which means they are widely used in various branches of industry. The ability to control the properties of nanoparticles makes these nanomaterials very interesting for medicine and pharmacology. The application of nanoparticles in medicine is associated with the design of specific nanostructures, which can be used as novel diagnostic and therapeutic modalities. There are a lot of applications of nanoparticles, e.g., as drug delivery systems, radiosensitizers in radiation or proton therapy, in bioimaging, or as bactericides/fungicides. This paper aims to introduce the characteristics of noble metal-based nanoparticles with particular emphasis on their applications in medicine and related sciences.


The product of the F plasmid transfer operon gene, traF, is a periplasmic protein.
The products of clones carrying the F plasmid transfer operon gene, traF, were analyzed. Proteins expressed in maxicells were labeled with [35S]methionine and examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Clones carrying the wild-type traF gene expressed two polypeptide products that were not products of clones containing the traF13 amber mutation. These migrated with apparent molecular weights (Ma) of 27,000 and 25,000. A pulse-chase experiment suggested that the larger product was a precursor of the smaller one. In the presence of ethanol, the Ma-27,000 polypeptide accumulated and the Ma-25,000 product was not expressed. These results indicated that the traF protein undergoes proteolytic processing associated with export. Cell fractionation experiments further indicated that the greatest concentration of the mature (Ma 25,000) TraF protein was located in the periplasm. The DNA sequence of traF and the position of the transition mutation in traF13 DNA were also determined. Sequence analysis suggested that traF would be expressed as a 247-amino-acid, Mr-28,006 polypeptide. The 19 amino acids at the amino terminus of this polypeptide appear to constitute a typical membrane leader peptide, while the remainder of the molecule (Mr 25,942) is predicted to be primarily hydrophilic in character.


Virtual high throughput screening (vHTS) on an optical high speed testbed.
Malaria remains a global health concern, which kills over a million people each year. In this paper we present work extending the approach of the WISDOM initiative by focusing on the problems noticed during the first WISDOM challenge against malaria and test the newly established, high bandwidth optical Grid environment VIOLA for advanced bioinformatics applications using the UNICORE middleware service. In addition we present an approach to reduce the size of the compound database to improve the efficiency of the screening.


Medulloblastoma in childhood: results of radical resection and low-dose neuraxis radiation therapy.
This review concerns 22 children who were treated from 1980 through 1983 for medulloblastoma in the posterior fossa. Treatment included attempts at radical resection of the tumor and postoperative craniospinal radiation therapy, with 5000 to 5500 rads directed to the posterior fossa and 2500 rads to the remaining craniospinal axis. This lower radiation dose to the neuraxis was used to avoid late adverse effects upon the growing central nervous system of the children. Gross confirmation of total resection was obtained in 13 patients (the "total resection group"); however, nine patients had a subtotal resection leaving a small portion of the tumor extending into the cerebellar peduncles or the cerebellopontine angle, or else encasing the posterior inferior cerebellar artery (the "subtotal resection group"). Six patients in the total resection group demonstrated tumor extension into the cerebellar peduncles, which was removed by means of a surgical carbon dioxide laser without neurological sequelae. Biopsy of the arachnoid membrane from the cisterna magna and cytological examination of the cerebrospinal fluid (CSF) prior to manipulation of the tumor were carried out in 12 patients. All but one showed dissemination of medulloblastoma cells. Myelography and CSF cytological study were undertaken 2 months after radiation therapy in 12 patients and were positive in two. There were no case mortalities in the total resection group during the 24- to 67-month follow-up period, whereas the 1-year survival rate in the "subtotal resection group" was only 44.4%. This study suggests that medulloblastoma can be controlled with a low radiation dose to the neuraxis, should a grossly confirmed total resection be achieved at craniotomy.


Bacteriologic and clinical efficacy of ofloxacin 0.3% versus ciprofloxacin 0.3% ophthalmic solutions in the treatment of patients with culture-positive bacterial keratitis.
To compare the efficacy and safety of ofloxacin 0.3% ophthalmic solution with ciprofloxacin 0.3% ophthalmic solution in patients with culture-positive bacterial keratitis. Patients with a microbiologic diagnosis of bacterial keratitis were included in this double-masked, parallel-group study and were randomized to treatment with either ofloxacin 0.3% or ciprofloxacin 0.3% ophthalmic solution. One drop of the study medication was instilled during the daytime according to the following schedule: every half-hour on study day 1, every hour on days 2 through 4, and every 2 hours on days 5 through 21. Healing, the primary outcome measure, was defined as complete reepithelialization, accompanied by nonprogression of stromal infiltrate for 2 days. Secondary outcome measures included signs and symptoms of infection. Patients were monitored throughout the study period for any adverse events. A total of 217 patients completed the study: 112 were treated with ofloxacin and 105 were treated with ciprofloxacin. Streptococcus pneumoniae was the most commonly encountered pathogen in all patients. Complete corneal reepithelialization occurred in 85% of those treated with ofloxacin and in 77% of those treated with ciprofloxacin (p = 0.32). The average time to corneal ulcer healing was 13.7 days in those treated with ofloxacin and 14.4 days in those treated with ciprofloxacin. Both treatments were well tolerated with no patient discontinuing the study because of side effects. Ofloxacin 0.3% and ciprofloxacin 0.3% ophthalmic solutions are effective and safe in the treatment of patients with culture-positive bacterial keratitis.


Concerted evolution in the repeats of an immunomodulating cell surface protein, SOWgp, of the human pathogenic fungi Coccidioides immitis and C. posadasii.
Genome dynamics that allow pathogens to escape host immune responses are fundamental to our understanding of host-pathogen interactions. Here we present the first population-based study of the process of concerted evolution in the repetitive domain of a protein-coding gene. This gene, SOWgp, encodes the immunodominant protein in the parasitic phase of the human pathogenic fungi Coccidioides immitis and C. posadasii. We sequenced the entire gene from strains representing the geographic ranges of the two Coccidioides species. By using phylogenetic and genetic distance analyses we discovered that the repetitive part of SOWgp evolves by concerted evolution, predominantly by the mechanism of unequal crossing over. We implemented a mathematical model originally developed for multigene families to estimate the rate of homogenization and recombination of the repetitive array, and the results indicate that the pattern of concerted evolution is a result of homogenization of repeat units proceeding at a rate close to the nucleotide point mutation rate. The release of the SOWgp molecules by the pathogen during proliferation may mislead the host: we speculate that the pathogen benefits from concerted evolution of repeated domains in SOWgp by an enhanced ability to misdirect the host's immune system.


Characterization of effects of zearalenone in swine during early pregnancy.
Mature gilts (n = 16) were hand mated and randomly assigned to 1 of 4 groups of 4 gilts each. Treated gilts had 108 mg of purified zearalenone added to their diet on postmating days (PMD) 2 to 6, 7 to 10, or 11 to 15. Control gilts were given the same diet without added zearalenone. On PMD 6, 10, and 15, control gilts had venous cannulas placed in the jugular vein, and blood samples were taken at 20-minute intervals for 4 hours before feeding and 4 hours after feeding. Samples were collected from treated gilts on the last day that zearalenone was consumed. Samples were analyzed for follicle stimulating hormone, luteinizing hormone (LH), and prolactin. Single blood samples were taken by venipuncture on PMD 8, 12, 16, 20, 24, and 28 and at euthanasia and were analyzed for serum concentration of progesterone and estradiol-17 beta. All gilts were euthanatized 30 to 32 days after mating, and fetal development was assessed. Three gilts that were given zearalenone on PMD 7 to 10 were not pregnant and had regressing corpora lutea on the ovaries at euthanasia. All other treated and control gilts were pregnant. Serum samples from treated gilts on PMD 10 and 15 had lower mean prolactin concentrations than did those from controls. The number of LH spikes were fewer (P less than 0.05) in gilts that were given zearalenone on PMD 15 compared with those in controls on PMD 15. Serum progesterone concentrations indicated that corpora lutea regressed between PMD 20 and 28 in nonpregnant gilts.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of respiratory physiologic features when infants are placed in car safety seats or car beds.
The objective of this study was to compare the respiratory physiologic features of healthy term infants placed in either a car bed or a car safety seat. Within the first 1 week of life, 67 healthy term infants were recruited and assigned randomly to be monitored in either a car bed (33 infants) or a car safety seat (34 infants). Physiologic data, including oxygen saturation and frequency and type of apnea, were obtained and analyzed in a blinded manner. The groups spent similar amounts of time in the devices (car bed: 71.6 minutes; car seat: 74.2 minutes). The mean oxygen saturation values were not different between the groups (car bed: 97.1%; car seat: 97.3%). The percentages of time with oxygen saturation of < 95% were also similar for the 2 groups (car bed: 11.8[corrected]%; car seat: 18.3[corrected]%). In both groups, a number of infants spent high percentages of study time with oxygen saturation of < 95%. The 6 infants with the most time at this level were all in the car safety seat group (54%-63% of study time). Values for the 6 infants in the car bed group with the most time at this level were lower (20%-42%). This difference in the duration of oxygen saturation of < 95% was not statistically significant. The mean end-tidal carbon dioxide levels and the numbers of episodes of apnea were similar for the 2 groups. The respiratory physiologic features of infants in the 2 car safety devices were observed to be similar. Of note, substantial periods of time with oxygen saturation of < 95% were surprisingly common in both groups.


Prevalence study to elucidate the transmission pathways of Helicobacter pylori at oral and gastroduodenal sites of a South Indian population.
Since the discovery of Helicobacter pylori (H. pylori), much progress has been made worldwide in the field of its epidemiology. In spite of these advancements, many aspects of epidemiology still remain unclear, particularly among populations with low socio-economic status. The present study was designed to elucidate the different routes of transmission of H. pylori in the Hyderabad (South India) population and to investigate the impact of certain factors, such as age, gender, and lifestyle. Samples used for the study included saliva and biopsy samples of 400 symptomatic subjects from Hyderabad, India. The patients were retrospectively grouped, based on histopathology of the biopsy and 16S rRNA amplification of both saliva and biopsy as H. pylori positive and negative. This study showed that the prevalence of H. pylori in both saliva and biopsy samples increased with age. In addition, the H. pylori infection was found more commonly in the saliva and biopsy samples among males (64 percent and 60 percent, respectively) than females (53.3 percent and 64 percent, respectively). Similarly, 71.6 percent and 73.5 percent of those who consumed municipal water acquired H. pylori (which were respectively found in their saliva and biopsy samples) compared to a lesser proportion (12.6 percent and 12.6 percent, respectively) of those who consumed boiled or filtered water. The study also found that subjects who preferred home-cooked food (57.1 percent and 57.7 percent) showed a lower prevalence of H. pylori in saliva and biopsy samples, respectively, compared to those (80 percent and 88 percent) who frequently ate out. The results of the present study suggest that besides the oral-oral route, the transmission of H. pylori also takes place through the consumption of food prepared under unhygienic conditions. Consumption of municipal tap water also has a high impact in the transmission of H. pylori.


[Relationship between electronic structure and eadioprotective activity of some indazoles].
Quantum chemical MNDO study of electronic structure for 29 indazoles has been performed. Statistically significant quantitative relation between some characteristics obtained and radioprotective activity was found out. Indazole structures which data predicted for radioprotective activity (survival, %) are on 50% level or more are proposed.


A matched case-control study of a novel Acid-pump antagonist and proton-pump inhibitor for the treatment of iatrogenic ulcers caused by endoscopic submucosal dissection.
Revaprazan, a novel acid-pump antagonist, and proton-pump inhibitors (PPIs) have pH-independent effects on ulcer healing. The addition of a PPI promotes the cell restitution rate as well as vessel regeneration and maturation for ulcer repair. Revaprazan is known to protect the mucosa by increasing the prostaglandin concentration. We reviewed the medical records of patients who underwent endoscopic submucosal dissection (ESD) for gastric neoplasia at Yeungnam University Hospital between January 2008 and May 2009. We conducted a matched case-control study to compare the healing rates effected by revaprazan and rabeprazole. Each group consisted of 30 patients. The baseline characteristics did not differ significantly between the two groups. Stage S1 disease was observed in 97% and 100% of patients after 8 weeks of treatment in the revaprazan and rabeprazole groups, respectively. In the revaprazan group, only one patient had stage H2 disease: a 54-year-old man with a 5.5-cm lesion after ESD of the ulcer, type IIa early gastric cancer, and adenocarcinoma. No serious adverse effects occurred during the treatment period in either group. The safety and efficacy profiles of revaprazan and rabeprazole are similar for the treatment of ESD-induced ulcers.


Exploring the Validity Based on Internal Structure of the Oldenburg Burnout Inventory - Medical Student (OLBI-MS).
The study gathers validity evidence for the use of the Oldenburg Burnout Inventory - Medical Student (OLBI-MS), a 16-item scale used to measure medical student burnout. The 16 items on the OLBI-MS are split to form two subscales, disengagement and exhaustion. Medical student burnout has been empirically linked to several detrimental professional and personal consequences. In recognition of the high prevalence of medical student burnout, one recommendation has been to regularly measure burnout using standardized measures that have strong validity evidence for their intended use. The OLBI-MS, a frequently used measure of medical student burnout, was adapted from the Oldenburg Burnout Inventory (OLBI). The OLBI has been studied in many occupational settings and been found to have a two-factor solution in majority of these populations, but there is limited validity evidence available that supports the use of the OLBI-MS subscales in a medical student population. Two years of Association of American Medical College Year 2 Questionnaire data (n = 24,008) were used in the study for a series of exploratory and confirmatory factor analyses. The data from the first year (n = 11,586) was randomly split into a confirmatory and exploratory sample, with the data from the second year (n = 12,422) used as a secondary confirmatory sample. Because the questionnaire is administered to medical students during their second year of undergraduate medical education, we consider this a study as providing validity evidence specifically for the measure's use with that population. The two-factor structure of the OLBI-MS was not empirically supported in the second year medical-student population. Several of the items had low inter-item correlations and/or moderate correlations with unexpected items. Three modified versions of the OLBI-MS were tested using subsets of the original items. Two of the modified versions were adequate statistical explanations of the relationships in the data. However, it is unclear if these revised scales appropriately measure all aspects of the construct of burnout and additional validity evidence is needed prior to their use. The use of the OLBI-MS is not recommended for measuring second-year medical student burnout. It is unclear if the OLBI-MS is appropriate for medical students at all, or if different measures are necessary at different stages in a medical student's professional development. Additional research is needed to either improve the OLBI-MS or use it as a foundation for a new measure. Supplemental data for this article is available online at at www.tandfonline.com/htlm .


Development, reliability, and validity of the Posttraumatic Stress Disorder Interview for Vietnamese refugees: a diagnostic instrument for Vietnamese refugees.
The Posttraumatic Stress Disorder Interview for Vietnamese Refugees (PTSD-IVR) was created specifically to assess for the presence of current and lifetime history of premigration, migration, encampment, and postmigration traumas in Vietnamese refugees. The purpose of the present study was to describe the development of and investigate the interrater and test-retest reliability of the PTSD-IVR and its validity in relation to the diagnoses obtained from the Longitudinal, Expert, and All Data (LEAD; Spitzer, 1983) standard. Clinicians conducted the diagnosis process with 127 Vietnamese refugees using the LEAD standard and the PTSD-IVR. Assessment of the reliability and validity of the PTSD-IVR yielded good to excellent AUC (area under the receiver operating characteristic curve; .86, .87) and κ values (.66, .74) indicating the reliability of the PTSD-IVR and the agreement between the LEAD procedure and the PTSD-IVR. The results of the present study suggest that the PTSD-IVR performs successfully as a diagnostic instrument specifically created for Vietnamese refugees in their native language.


ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates.
Ethionamide (ETH) is a structural analog of the antituberculosis drug isoniazid (INH). Both of these drugs target InhA, an enzyme involved in mycolic acid biosynthesis. INH requires catalase-peroxidase (KatG) activation, and mutations in katG are a major INH resistance mechanism. Recently an enzyme (EthA) capable of activating ETH has been identified. We sequenced the entire ethA structural gene of 41 ETH-resistant Mycobacterium tuberculosis isolates. We also sequenced two regions of inhA and all or part of katG. The MICs of ETH and INH were determined in order to associate the mutations identified with a resistance phenotype. Fifteen isolates were found to possess ethA mutations, for all of which the ETH MICs were > or =50 microg/ml. The ethA mutations were all different, previously unreported, and distributed throughout the gene. In eight of the isolates, a missense mutation in the inhA structural gene occurred. The ETH MICs for seven of the InhA mutants were > or =100 microg/ml, and these isolates were also resistant to > or =8 microg of INH per ml. Only a single point mutation in the inhA promoter was identified in 14 isolates. A katG mutation occurred in 15 isolates, for which the INH MICs for all but 1 were > or =32 microg/ml. As expected, we found no association between katG mutation and the level of ETH resistance. Mutations within the ethA and inhA structural genes were associated with relatively high levels of ETH resistance. Approximately 76% of isolates resistant to > or =50 microg of ETH per ml had such mutations.


Meeting Abstracts - AMCP 2020.
The abstracts presented in this program were originally slated to be presented at the AMCP 2020 meeting in Houston, Texas, April 21-24. The meeting was canceled because of the COVID-19 crisis. In lieu of the scheduled poster presentations, many poster presenters have shared additional information about their research at https://plan.core-apps.com/amcp2020. Professional abstracts that have been reviewed are published in the Journal of Managed Care & Specialty Pharmacy's Meeting Abstracts supplement.


A computer-based method for continuous single pulse analysis of intracranial pressure waves.
The single pulse analysis of intracranial pressure waves provides valuable information about the autoregulative processes after head injury. This method has not been used for routine clinical assessment as yet. Current methods for evaluation of intracranial pressure waves are based on spectral analysis or related techniques. This imposes restrictions on the wave sequences available for the investigation of ICP attributes. Therefore, we have developed a computer-based method, which enables continuous analysis of each pulse of the ICP wave, in any clinical setting. Firstly, the raw data of the ICP wave is continuously recorded by the Multifunctional Anaesthetic Record System (MARS, Hewlett Packard). The recorded data is then subjected to single pulse wave analysis by our software. Each single pulse is identified by the algorithm. The maximum, minimum and mean value, as well as amplitude and gradient are calculated in each pulse pressure. All conceivable correlations of the listed parameters can be examined. We applied our software in 9 cases with head injury and evaluated the measurements over 59 days (1400 h). More than 7 million single pulse pressures have been analyzed off-line. The software proved to be accurate and easy to apply. It was possible to calculate correlations between the different wave attributes on a broad basis of data. Parameters of special clinical interest were the amplitude of the single pulse pressure and the gradient. This method is an improvement on ICP single pulse pressure analysis and facilitates its clinical application. It creates the possibility for continuous long-term analysis of the ICP wave attributes under any clinical condition without loss of data. There are indications that the amplitude and the gradient of the ICP pulse pressure could provide valuable additional information for clinical assessment. However, further evaluation is required.


Emergence of Homochiral Benzene-1,3,5-tricarboxamide Helical Assemblies and Catalysts upon Addition of an Achiral Monomer.
Chirality amplification refers to the ability of a small chiral bias to fully control the main chain helicity of polymers and assemblies. Further implementation of functional chirally amplified helices as switchable asymmetric catalysts, chiral sensors, and circularly polarized light emitters will require a greater control of the energetics governing these chirality amplification effects. In this work, we report on the counterintuitive ability of an achiral molecule to suppress conformational defects in supramolecular helices, thus leading to the emergence of homochirality in a system containing a very small chiral bias. We focus our investigation on supramolecular helices composed of an achiral benzene-1,3,5-tricarboxamide (BTA) ligand, coordinated to copper, and an enantiopure BTA comonomer. Amplification of chirality as probed by varying the amount (sergeants and soldiers effect) or the optical purity (diluted majority-rules effect) of the enantiopure comonomer are modest in this initial system. However, both effects are hugely enhanced upon addition of a second achiral BTA monomer, leading to a perfect control of the helicity either by means of a remarkably low amount of sergeants (0.5%) or a small bias from a racemic mixture of enantiopure comonomers (10% ee). Such an enhancement in the amplification of chirality is only achieved by mixing the three components, i.e. the two achiral and the enantiopure comonomers, highlighting a synergistic effect upon coassembly of the three monomers. Investigation of the role of the achiral additive by multifarious analytical techniques supports its ability to stabilize the helical coassemblies and suppress helix reversals: i.e., conformational defects. Implementation of these helical copper precatalysts in the hydrosilylation of 1-(4-nitrophenyl)ethanone confirms that the effect of the achiral BTA additive is also operative under the conditions of the catalytic experiment. A highly enantioenriched product (90% ee) is produced by a supramolecular catalyst operating with ppm levels of chiral species.


The Phenylephrine Test Revisited.
To characterize the phenylephrine test in ptotic patients to help clinicians perform the test more efficiently. Adults with involutional ptosis (n = 24, 30 eyes) were assessed with digital photographs for response to topical 2.5% phenylephrine drop instillation. Patient characteristics (age, gender, iris color, dermatochalasis, brow ptosis, and baseline marginal reflex distance-1 [MRD-1] height) were recorded. From the photographs, change in (MRD-1), presence of conjunctival blanching, pupillary dilation, and Hering effect were recorded at specified time intervals, 1 minute to 1 hour after drop placement. Correlations between patient characteristics and measured outcomes were evaluated using analysis of variance, Pearson coefficient, or chi-square tests. The authors found that 73% of eyes had eyelid elevation with phenylephrine. Of these, 50% reached maximal eyelid elevation by 5 minutes, and 86% by 10 minutes after drop placement, but 14% did not reach maximal MRD-1 until 30 minutes. There is a negative correlation between the maximum MRD-1 and the baseline MRD-1 eyelid height (r = -0.5330, p < 0.01). There is no significant relationship between time to pupillary dilation with either time to max eyelid elevation or max eyelid elevation. No patient characteristic studied affected the likelihood of eyelid response to phenylephrine or presence of Hering effect. Although most ptotic eyelids demonstrate a response to 2.5% phenylephrine within 10 minutes, there is a subset of patients that respond much later. More ptotic eyelids had greater eyelid elevation with phenylephrine. Pupillary dilation and conjunctival blanching are neither predictive of nor temporally associated with eyelid height elevation. The authors did not identify any patient factors (e.g., dermatochalasis, brow ptosis) that can predict the likelihood of response to phenylephrine.


Single morning and nightly doses of ranitidine 300 mg: an appraisal of their antisecretory effects by continuous pH monitoring.
Gastric acidity of 12 patients with healed duodenal ulcers was continuously monitored over 24 h in order to assess the antisecretory effects of two different administration times of a single daily dose of ranitidine 300 mg. Each patient orally received either (a) placebo at 08.00 h and 22.00 h; (b) ranitidine 300 mg at 08.00 h and placebo at 22.00 h, or (c) placebo at 08.00 h and ranitidine 300 mg at 22.00 h in randomized and double-blind fashion. Each medication was administered on three separate occasions, with intervals of at least 1 week. Both the morning and the bedtime doses of ranitidine were significantly superior (p less than 0.001) to placebo in controlling 24-hour gastric acidity, while, in the same period, ranitidine nocte was more effective (p less than 0.001) than ranitidine mane. During the night, bedtime ranitidine caused more acid inhibition (p less than 0.001) than morning ranitidine, but the opposite (p less than 0.01) occurred during the daytime. This study shows that the antisecretory effect of morning ranitidine during the daytime is less consistent than that achieved by bedtime ranitidine during the nocturnal period. As similar rates of duodenal ulcer healing have recently been achieved with morning and conventional nighttime administration of H2 antagonists, it becomes clear that antisecretory drugs can also be beneficial with an acid inhibition which is shorter-lasting than that which was previously thought to be necessary or, alternatively, that also daytime acidity is important in ulcerogenesis.


Gordonia alkanivorans sp. nov., isolated from tar-contaminated soil.
Twelve bacterial strains isolated from tar-contaminated soil were subjected to a polyphasic taxonomic study. The strains possessed meso-diaminopimelic acid as the diagnostic diamino acid of the peptidoglycan, MK-9(H2) as the predominant menaquinone, long-chain mycolic acids of the Gordonia-type, straight-chain saturated and monounsaturated fatty acids, and considerable amounts of tuberculostearic acid. The G + C content of the DNA was 68 mol%. Chemotaxonomic and physiological properties and 16S rDNA sequence comparison results indicated that these strains represent a new species of the genus Gordonia. Because of the ability of these strains to use alkanes as a carbon source, the name Gordonia alkanivorans is proposed. The type strain of Gordonia alkanivorans sp. nov. is strain HKI 0136T (= DSM 44369T).


Acute Coronary Syndrome
Rupture of an atherosclerotic plaque is the usual initiating event in an acute coronary syndrome (ACS). Persistent thrombotic occlusion at the site of plaque rupture results in acute myocardial infarction. The early management of the patient is essential and crucially affects the prognosis of an ACS. Management includes the relief of ischemic pain and the initiation of an antithrombotic therapy, including an antiplatelet and anticoagulant therapy with aspirin and heparin to prevent further thrombosis of or embolism from an ulcerated plaque.


Comprehensive CYP2D6 genotype and adherence affect outcome in breast cancer patients treated with tamoxifen monotherapy.
The association between CYP2D6 genotype and outcome in breast cancer patients treated with adjuvant tamoxifen remains controversial. We assessed the influence of comprehensive versus limited CYP2D6 genotype in the context of tamoxifen adherence and co-medication in a large cohort of 618 patients. Genotyping of 33 CYP2D6 alleles used two archival cohorts from tamoxifen-treated women with invasive breast cancer (Dundee, n = 391; Manchester, n = 227). Estimates for recurrence-free survival (RFS) were calculated based on inferred CYP2D6 phenotypes using Kaplan-Meier and Cox proportional hazard models, adjusted for nodal status and tumour size. Patients with at least one reduced function CYP2D6 allele (60%) or no functional alleles (6%) had a non-significant trend for worse RFS: hazard ratio (HR) 1.52 (CI 0.98-2.36, P = 0.06). For post-menopausal women on tamoxifen monotherapy, the HR for recurrence in patients with reduced functional alleles was 1.96 (CI 1.05-3.66, P = 0.036). However, RFS analysis limited to four common CYP2D6 allelic variants was no longer significant (P = 0.39). The effect of CYP2D6 genotype was increased by adjusting for adherence to tamoxifen therapy, but not significantly changed when adjusted for co-administration of potent inhibitors of CYP2D6. Comprehensive genotyping of CYP2D6 and adherence to tamoxifen therapy may be useful to identify breast cancer patients most likely to benefit from adjuvant tamoxifen.