First Report of Peronospora farinosa f. sp. spinaciae Causing Downy Mildew on Spinach in Egypt.
Downy mildew, caused by Peronospora farinosa f. sp. spinaciae (= P. effusa) is an economically important disease in most areas where spinach is grown. This disease has become increasingly important in intensive production fields for pre-packaged salad mixes where plant densities typically are very high (2). However, little is known about race diversity of the downy mildew pathogen of spinach in smaller (<1 ha) production areas. Small (~0.1 ha) spinach production fields in Fayoum, Egypt, often intercropped with lettuce, were examined in February 2013. Downy mildew was observed in three spinach fields in the Fayoum area. Most of the cultivars being grown were traditional cultivars commonly grown from locally produced open pollinated seed. Disease incidence was relatively low with only about 10% of the plants showing symptoms of infection. Symptoms of downy mildew were observed on the cultivar Meky, and included chlorotic spots with blue-gray sporulation on the underside of the symptomatic leaves. Microscopic examination revealed sporangia, measuring 20.2 × 30.5 μm, and monopodial sporangiaphores of 180 to 330 μm length matching the description of P. farinosa f. sp. spinaciae (1). In addition, the pathogen was identified by examination of the nuclear ribosomal DNA (rDNA) internal transcribed spacer (ITS) sequence, which had 100% identity to a 762-bp ITS sequence in GenBank of P. farinosa f. sp. spinaciae (Accession No. DQ643879.1). The Fayoum area of Egypt gets relatively low annual rainfall, typically <10 to 15 cm annually, often concentrated in the winter months of November to February, followed by very hot, dry summer months. Although downy mildew of spinach has been reported in Israel, adjacent to Egypt, the disease apparently is relatively rare in the arid Middle East (3). This is the first known report of downy mildew of spinach in Egypt. References: (1) Y. Choi et al. Mycol. Res. 111:318, 2007. (2) J. C. Correll et al. Eur. J. Plant Pathol. 2011. (3) T. Rayss. Palest. J. Bot. Jerusalem Ser. 1:313, 1938.


Effect of Osteoporosis Medication on Fracture Healing: An Evidence Based Review.
A systematic search was conducted and relevant studies that evaluated the influence of osteoporosis medications (bisphosphonates [BPs], denosumab, selective estrogen receptor modulators [SERMs], recombinant human parathyroid hormone teriparatide [TPTD], and strontium ranelate [SrR]) on wrist, hip, and spine fracture healing, were selected. BPs administration did not influence fracture healing and clinical outcomes after distal radius fracture (DRF). Similar results were observed in hip fracture, but evidence is lacking for spine fracture. Denosumab did not delay the non-vertebral fractures healing in one well-designed study. No studies evaluated the effect of SERMs on fracture healing in humans. One study reported shorter fracture healing times in TPTD treated DRF patients, which was not clinically meaningful. In hip fracture, recent studies reported better pain and functional outcomes in TPTD treated patients. However, in spine fracture, recent studies found no significant differences in fracture stability between TPTD treated patients and controls. Evidence is lacking for SrR, but it did not influence wrist fracture healing in one study. In comparisons between TPTD and BPs, fracture healing and physical scores were not significantly different in hip fracture by 1 study. In spine fracture, controversy exists for the role of each medication to the fracture stability, but several studies reported that fracture site pain was better in TPTD treated patients than BPs treated patients. Considering no clinical data of negative fracture healing of the antiresorptive medication and the danger of subsequent fracture after initial osteoporotic fracture, there is no evidence to delay initiation of osteoporosis medications after fracture.


Remote data collection speech analysis and prediction of the identification of Alzheimer's disease biomarkers in people at risk for Alzheimer's disease dementia: the Speech on the Phone Assessment (SPeAk) prospective observational study protocol.
Identifying cost-effective, non-invasive biomarkers of Alzheimer's disease (AD) is a clinical and research priority. Speech data are easy to collect, and studies suggest it can identify those with AD. We do not know if speech features can predict AD biomarkers in a preclinical population. The Speech on the Phone Assessment (SPeAk) study is a prospective observational study. SPeAk recruits participants aged 50 years and over who have previously completed studies with AD biomarker collection. Participants complete a baseline telephone assessment, including spontaneous speech and cognitive tests. A 3-month visit will repeat the cognitive tests with a conversational artificial intelligence bot. Participants complete acceptability questionnaires after each visit. Participants are randomised to receive their cognitive test results either after each visit or only after they have completed the study. We will combine SPeAK data with AD biomarker data collected in a previous study and analyse for correlations between extracted speech features and AD biomarkers. The outcome of this analysis will inform the development of an algorithm for prediction of AD risk based on speech features. This study has been approved by the Edinburgh Medical School Research Ethics Committee (REC reference 20-EMREC-007). All participants will provide informed consent before completing any study-related procedures, participants must have capacity to consent to participate in this study. Participants may find the tests, or receiving their scores, causes anxiety or stress. Previous exposure to similar tests may make this more familiar and reduce this anxiety. The study information will include signposting in case of distress. Study results will be disseminated to study participants, presented at conferences and published in a peer reviewed journal. No study participants will be identifiable in the study results.


Immunocytochemical demonstration of a SALMFamide-like neuropeptide in the nervous system of adult and larval stages of the human blood fluke, Schistosoma mansoni.
The localization and distribution of SALMFamide immunoreactivity (IR), SI(GFNSALMFamide), in the nervous system of both the adult and larval stages of the trematode Schistosoma mansoni has been determined by an indirect immunofluorescent technique in conjunction with confocal scanning laser microscopy (CSLM). Immunostaining was widespread in the nervous system of adult male and female S. mansoni. In the central nervous system (CNS), IR was evident in nerve cells and fibres in the anterior ganglia, cerebral commissure and dorsal and ventral nerve cords. In the peripheral nervous system (PNS), IR was apparent in nerve plexuses associated with the subtegmental musculature, oral and ventral suckers, the lining of the gynaecophoric canal, and in fine nerve fibres innervating the dorsal tubercles of the male worm. In the reproductive system of male and female worms, S1-IR was only observed around the ootype/Mehlis' gland complex in the female. Immunostaining was also evident in the nervous system of both miracidium and cercarial larval stages. A post-embedding, IgG-conjugated colloidal gold immunostaining technique was employed to examine the subcellular distribution of SALMFamide-IR in the CNS of S. mansoni. Gold labelling of peptide was localized over dense-cored vesicles within nerve cell bodies and fibres constituting the neuropile of the anterior ganglia, cerebral commissure and nerve cords of the CNS. Antigen pre-absorption studies indicated that the results obtained do suggest S1-like immunostaining and not cross-reactivity with other peptides, in particular FMRFamide.


Enhancing the Treatment of Patients With Schizophrenia Through Continuous Care.
Schizophrenia is a chronic disorder that can be effectively controlled but will likely require lifelong treatment. Unfortunately, most patients experience numerous relapses, ongoing symptoms, and impairment, often because of treatment interruptions. Continuous treatment is imperative to prevent relapse and the potentially devastating consequences that can follow a return of psychotic symptoms. Clinicians must better monitor a common cause of relapse, nonadherence, and offer strategies to improve adherence. Strategies can target the patient, the environment, or treatment. One treatment-related strategy is the use of long-acting injectable (LAI) antipsychotics, which have the potential to reduce relapse and rehospitalization for many patients with schizophrenia.


Linking phenomenon during atrial stimulation with accessory pathways.
Linking is an electrophysiologic phenomenon in which each successive impulse entering a macroreentry circuit propagates preferentially along 1 limb because of the functional impedance to conduction in the contralateral limb produced by the previous impulse. Electrophysiologic studies were performed in 12 patients with a bidirectionally conducting accessory pathway. Linking was analyzed while 1:1 atrioventricular conduction took place through the normal pathway. When atrial pacing (at the same cycle length) could be initiated during sinus rhythm in patients with rapidly conducting accessory pathways, linking was dynamically maintained by repetitive local refractoriness (interference). When it could be initiated during the usual type of orthodromic circus movement tachycardia, linking was sustained by actual impulse collision, the underlying mechanism having also been called entrainment. When it could be initiated during sinus rhythm in a patient with a slowly conducting accessory pathway, linking was maintained by impulse collision, but the underlying mechanism could not be called entrainment because stimulation had not been started during tachycardia. This study showed that 2 terms--linking and entrainment--may be applied to the same mechanism and, conversely, that the same name could not be used in reference to the same mechanism when pacing was initiated under different circumstances. However, using the proposed conceptual formulation for linking, it is apparent that seemingly diverse mechanisms associated with macroreentry circuits involving accessory pathways are, in fact, variations on a common electrophysiologic theme.


Pure-tone audiometry without bone-conduction thresholds: using the digits-in-noise test to detect conductive hearing loss.
Objective: COVID-19 has been prohibitive to traditional audiological services. No- or low-touch audiological assessment outside a sound-booth precludes test batteries including bone conduction audiometry. This study investigated whether conductive hearing loss (CHL) can be differentiated from sensorineural hearing loss (SNHL) using pure-tone air conduction audiometry and a digits-in-noise (DIN) test.Design: A retrospective sample was analysed using binomial logistic regressions, which determined the effects of pure tone thresholds or averages, speech recognition threshold (SRT), and age on the likelihood that participants had CHL or bilateral SNHL.Study sample: Data of 158 adults with bilateral SNHL (n = 122; PTA0.5-4 kHz > 25 dB HL bilaterally) or CHL (n = 36; air conduction PTA0.5-4 kHz > 25 dB HL and ≥20 dB air bone gap in the affected ears) were included.Results: The model which best discriminated between CHL and bilateral SNHL used low-frequency pure-tone average (PTA), diotic DIN SRT, and age with an area under the ROC curve of 0.98 and sensitivity and specificity of 97.2 and 93.4%, respectively.Conclusion: CHL can be accurately distinguished from SNHL using pure-tone air conduction audiometry and a diotic DIN. Restrictions on traditional audiological assessment due to COVID-19 require lower touch audiological care which reduces infection risk.


"A comparison between sugar consumption and ethanol production in wort by immobilized Saccharomyces Cerevisiae, Saccharomyces Ludwigii and Saccharomyces Rouxii on Brewer'S Spent Grain".
The immobilization of Saccharomyces cerevisiae DSM 70424, Saccharomyces ludwigii DSM 3447 and Saccharomyces rouxii DSM 2531 on brewer's spent grain and then ethanol production and sugar consumption of these immobilized yeasts were investigated. The aim of this study was to investigate the abilities of these three immobilized yeasts for producing alcohol for brewing at two temperatures (7 and 12 °C) using two different sugar levels (one at original level supplied in the brewery and one with 2.5% (w/v), added glucose to the wort). Increasing both parameters resulted in higher alcohol production by all the yeasts studied. At 7 °C and with original wort density the ethanol content at the end of fermentation was 2.7% (v/v) for S. cerevisiae, 1.7% for S. ludwigii and 2.0% for S. rouxii. After the addition of 2.5% (w/v) glucose at the same temperature (7 °C), the alcohol production was increased to 4.1, 2.8 and 4.1%, respectively. Similar improvements were observed when the fermentation was carried out at 12 °C with/without the addition of glucose to the wort. However, temperature indicated greater influence on S. ludwigii than did on S. rouxii and S. cerevisiae. The immobilization as carried out in this study impacted both S. ludwigii and S. rouxii in a way that they could consume maltose under certain conditions.


A peroxide/ascorbate-inducible catalase from Haemophilus influenzae is homologous to the Escherichia coli katE gene product.
Bacterial catalases are induced by exposure to peroxide (e.g., Escherichia coli katG) or entry into stationary phase (e.g., E. coli katE). To study regulatory systems in Haemophilus influenzae, we complemented an E. coli rpoS mutant, which is unable to induce katE in stationary phase, with a plasmid library of H. influenzae Rd- chromosomal DNA. Nineteen complementing clones with a catalase-positive phenotype were obtained and characterized after screening about 10(5) transformants. All carried the same structural gene for an H. influenzae catalase. The DNA sequence of this gene, called hktE, encodes a 508-amino-acid polypeptide with strong homology to eukaryotic catalases and E. coli katE. However, hktE is regulated like E. coli katG, with catalase activity increasing 10-fold and hktE mRNA levels increasing 4-fold upon exposure to ascorbic acid, which serves to generate hydrogen peroxide. Mutations in the known global regulatory genes of H. influenzae--crp, cya, and sxy--do not affect the inducibility of hktE. The hktE gene maps to a 225-kb segment of the H. influenzae chromosome in a region encoding resistance to spectinomycin.


The feasibility of cardiopulmonary exercise testing for prescribing exercise to people after stroke.
Despite the importance of exercise training in mitigating cardiovascular risk, the development of exercise programs for people poststroke has been limited by lack of feasibility data concerning cardiopulmonary exercise testing (CPET) to inform the exercise prescription. Therefore, we examined the feasibility of CPETs for developing an exercise prescription in people ≥3 months poststroke. CPET results from 98 consecutively enrolled patients poststroke with motor impairments and 98 age- and sex-matched patients with coronary artery disease were examined at baseline and after 6 months of exercise training. The proportion of patients with stroke and coronary artery disease attaining an intensity sufficient for prescribing exercise at baseline was 68.4% versus 82.7%, respectively (P=0.02) and 84.7% versus 83.8% (P=0.9) at 6 months. Women were less likely than men poststroke to achieve a sufficient intensity at baseline (40% versus 80.9%, P<0.001) but not at 6 months (78.3% versus 87.1, P=0.3). A clinically relevant abnormality occurred in 11.2% of stroke and 12.2% of patients with coronary artery disease on baseline CPETs (P=0.8) and 10.6% of stroke and 5.9% of patients with coronary artery disease on the 6-month CPET (P=0.4). No serious cardiovascular events occurred during 349 CPETs. Most patients after stroke achieved a level of exertion during the CPET sufficient to inform an exercise prescription. At least 1 of 10 patients poststroke developed a clinically relevant abnormality on baseline and postprogram CPETs with no serious cardiovascular events. These data support the feasibility and safety of CPETs for prescribing exercise poststroke. Strategies to improve use of baseline CPETs for women poststroke require further investigation.


Gallium-avid thymic hyperplasia in an adult after chemotherapy for Hodgkin disease.
This article presents the case of a 22-year-old patient with treated Hodgkin disease (HD) who had mediastinal widening on computed tomography scan after chemotherapy. This mass was gallium avid. These findings were explained by histologically documented benign thymic hyperplasia, the first such case reported in an adult with HD, to the knowledge of the authors. The literature on thymic hyperplasia after chemotherapy is reviewed.


Aspects of the value of continuous ambulatory ECG monitoring in the detection and management of ischaemic heart disease. Case reports.
In 2 patients admitted for evaluation of chest pain occurring mainly at rest, organic disease of the nondominant circumflex artery only, with normal left anterior descending and right coronary arteries, was demonstrated in each case. Continuous ambulatory ECG monitoring by the Holter system revealed episodes of ST-segment elevation probably due to coronary artery spasm, allowing specific treatment to be instituted. Some aspects of the value of continuous ambulatory Holter monitoring in patients with ischaemic heart disease are discussed.


The changing managerial role of physician executives.
A survey of tasks performed by a sample of 517 physician executives from the AMA Masterfile was carried out to determine the role played by this group of administrators in health care organizations. In contrast to the findings of previous studies, physician executives appear to have responsibilities in general management as well as clinical management and do not focus primarily on physician and medical staff issues. No significant differences were found among respondents from hospitals, government, academic organizations, group practices/HMOs, and physician executives who spend more than 90 percent of their time in administration. Tasks identified as important for the future but not currently being done were primarily in the category of external activities such as "changing regulations and legislation" and "communicating goals to the public." These results identify an important boundary-spanning role for physician executives in balancing managerial and professional issues of cost, quality, and access in health care organizations. The implications of these findings for the educational needs of physician executives are discussed.


[Incidence and prevalence of asbestos-related diseases in Croatia].
The aim of this study was to identify the incidence and prevalence of asbestos-related diseases in Croatia, based on the Hospital Morbidity Database and General Mortality Database of the Croatian National Institute of Public Health. Both databases cover a period from 2002 to 2007), and include information from the Register of Occupational Diseases. Diagnoses in focus were mesothelioma (C45), asbestosis, and pleural plaque (J61 and J92). Yearly rates of inpatients treated for mesothelioma, asbestosis, or pleural plaque that were higher than the Croatian average (2.1) were recorded in the Counties of Split-Dalmatia (5.0), Dubrovnik-Neretva (3.9), Istria (3.7), and Primorje-Gorski kotar (3.1 per 100,000 people). From 2002 to 2007, 649 occupational diseases were reported, out of which 11.7% were asbestos-related. The most frequent were pleural plaque with asbestosis (38 cases, 50.0%), pleural plaque (23 cases, 30.3%), and mesothelioma (6 cases, 7.9%). Mortality attributable to asbestos was assessed using official Croatian National Statistics Bureau reports for 2002 to 2007 at the county and national level. During that period, Croatia recorded 312 deaths with the average yearly rate of 1.2 per 100.000 people. Four counties had higher rates than the national average: Primorje-Gorski kotar (3.4), Split-Dalmatia (2.8), Istria (2.8), and S1. Brod-Posavina (1.5). The number of inpatients treated for asbestos-related diseases was higher than the national average in the counties of Split-Dalmatia, Dubrovnik-Neretva, and Primorje-Gorski Kotar. Mesothelioma incidence was above the national average in the counties of Split-Dalmatia, Primorje-Gorski Kotar, and Istria. The rates of occupational, asbestos-related diseases were higher than the national average in the counties of Split-Dalmatia and Primorje-Gorski Kotar. We were aware that the interpretation of data is somewhat limited by the relatively small absolute number of treated persons and deaths for the observed period, by the fact that crude rates have not been adjusted for total numbers and for regional differences in population distribution by age and gender. The real extent of asbestos-related burden in Croatian general population remains unknown, because only occupational exposure has been monitored. Therefore, the National Public Health Institute and county public health institutes should implement a specific monitoring programme in collaboration with government environmental bodies to assess asbestos exposure of the population living in the vicinity of asbestos plants. It is also necessary to establish the number of exposed persons who have developed an asbestos-related disease. Their health should be monitored and their environment inspected on a regular basis.


[Phage typing of nonagglutinating vibrios isolated in the territory of the USSR].
The work presents the results of the phage typing of 2,437 NAG vibrio strains isolated in the USSR from patients and carriers (374 strains), from open water basins (1,675 strains), from sewage (234 strains) and from bottom silt (172 strains). Phage typing was carried out with a set of 5 phages capable of lyzing enteropathogenic NAG vibrios (phages TEPV 1, 2, 3, 4, 5). NAG vibrios isolated from humans were sensitive to phages TEPV in 45% of cases and NAG vibrios isolated from the environment, only in 29.9% of cases. Enteropathogenic NAG vibrios belonging to phagovar 1 were isolated most frequently from samples taken both from humans and from the environment. The NAG vibrios isolated from patients, carriers and the sources of water supply nearest to them belonged to the same phagovars.


Validation and validity of diagnoses in the General Practice Research Database: a systematic review.
To investigate the range of methods used to validate diagnoses in the General Practice Research Database (GPRD), to summarize findings and to assess the quality of these validations. A systematic literature review was performed by searching PubMed and Embase for publications using GPRD data published between 1987 and April 2008. Additional publications were identified from conference proceedings, back issues of relevant journals, bibliographies of retrieved publications and relevant websites. Publications that reported attempts to validate disease diagnoses recorded in the GPRD were included. We identified 212 publications, often validating more than one diagnosis. In total, 357 validations investigating 183 different diagnoses met our inclusion criteria. Of these, 303 (85%) utilized data from outside the GPRD to validate diagnoses. The remainder utilized only data recorded in the database. The median proportion of cases with a confirmed diagnosis was 89% (range 24-100%). Details of validation methods and results were often incomplete. A number of methods have been used to assess validity. Overall, estimates of validity were high. However, the quality of reporting of the validations was often inadequate to permit a clear interpretation. Not all methods provided a quantitative estimate of validity and most methods considered only the positive predictive value of a set of diagnostic codes in a highly selected group of cases. We make recommendations for methodology and reporting to strengthen further the use of the GPRD in research.


Psychosocial factors influencing non-urgent use of the emergency room: a review of the literature and recommendations for research and improved service delivery.
Despite dramatic increases in use of hospital emergency rooms (ERs) since the 1950s, an estimated 85% of ER visits are made for non-life-threatening reasons. Using a modified version of the Andersen and Newman model of health care utilization, this paper reviews the research literature on ER use to examine what is known about factors that influence three stages of the help-seeking process: (1) problem recognition; (2) the decision to seek help; (3) the decision to use the ER. While predisposing factors other than race are not generally significant, enabling factors such as income, insurance coverage, having a usual source of care, and geographic proximity affect use of the ER, both alone and in interaction with race and other factors. The most common reason for non-urgent ER use was 'other care not available'. In addition to the absence of primary care, non-urgent use of the ER is linked to need factors arising from socioeconomic stress, psychiatric co-morbidities, and a lack of social support. Recommendations for future studies include examining prospectively all 3 stages of decision-making leading to ER use, and considering interactive effects among predictors. Implications for service delivery are discussed, including the need to re-structure health care delivery systems to provide greater access to primary care and provide more attention to psychosocial aspects of patient care in clinical settings.


Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin-dependent diabetes mellitus.
Normal subjects demonstrate the presence of ultradian oscillations (period 80-150 min) in insulin secretion rate (ISR) tightly coupled to glucose oscillations of similar period. These oscillations appear to be a function of the feedback loop linking glucose and insulin. The present study was undertaken to determine whether the control by glucose of the ultradian oscillations in insulin secretion is altered in impaired glucose tolerance IGT and in non-insulin-dependent diabetes mellitus (NIDDM). Patients with NIDDM (n = 7), IGT (n = 4), and matched nondiabetic controls (n = 5) were studied under three separate protocols that involved administration of glucose at either a constant rate of 6 mg/kg per min for 28 h or in one of two oscillatory patterns at the same overall mean rate. The amplitude of the oscillations was 33% above and below the mean infusion rate, and their respective periods were 144 min (slow oscillatory infusion) or 96 min (rapid oscillatory infusion). Insulin, C-peptide, and glucose were sampled at 10-min intervals during the last 24 h of each study. ISRs were calculated by deconvolution of C-peptide levels. Analysis of the data showed that (a) the tight temporal coupling between glucose and ISR in the nondiabetic controls was impaired in the IGT and NIDDM groups as demonstrated by pulse analysis, cross-correlation analysis, and spectral analysis; (b) the absolute amplitude of the ISR pulses progressively declined with the transition from obesity to IGT to NIDDM; and (c) the absolute amplitude of the ISR oscillations failed to increase appropriately with increasing absolute amplitude of glucose oscillations in the IGT and NIDDM subjects compared with the control group. In conclusion, the present study demonstrates that important dynamic properties of the feedback loop linking insulin secretion and glucose are disrupted not only in established NIDDM but also in conditions where glucose tolerance is only minimally impaired. Further studies are needed to determine how early in the course of beta-cell dysfunction this lack of control by glucose of the ultradian oscillations in insulin secretion occurs and to define more precisely if this phenomenon plays a pathogenetic role in the onset of hyperglycemia in genetically susceptible individuals.


[The treatment of bronchopulmonary aspergillosis with allergic manifestations].
The base of current management of bronchopulmonary aspergillosis with allergic manifestations (BPAAM) is glucocorticosteroid treatment. These hormones are introduced in a mean dose 0.5 mg/kg (by prednisolone) to correct bronchial obstruction, reduce eosinophilia and resolve (completely or partially) infiltrates in the lungs. This being achieved, the dose is lowered to warrant maintenance. Minimal doses or discontinuation of glucocorticosteroids may be used in case of adjuvant indomethacin (0.025 three times a day) or plasmapheresis administration. In remission, fungistatic means with glucocorticosteroids or without them (in the absence of bronchial obstruction) are proper. Inhalations in BPAAM are ineffective. Individual schemes of the disease treatment may vary in wide range.


Delegating responsibility from clinicians to nonprofessional personnel: the example of hypertension control.
Involving nonclinician personnel in the treatment of hypertension may provide a solution to improve blood pressure control; however, this team-based approach cannot be implemented without first determining clinicians' willingness to delegate patient care to nonclinician team members. This study explores clinicians' perspectives on working with nonclinicians trained as "health coaches" to address medication adherence and lack of medication intensification among low-income patients with uncontrolled hypertension. We used a qualitative research approach to determine clinicians' opinions on the Treat-to-Target study, an intervention to improve blood pressure control. We conducted focus groups with clinicians who practice family medicine in a safety net clinic. Transcripts were analyzed using thematic content analysis. Seven overarching themes emerged: (1) Clinicians support the delegation of functions to health coaches; (2) clinicians like the high frequency of coach-patient interactions; (3) clinicians feel that health coaching assists medication adherence; (4) clinicians have varying views on home titration; (5) coach-clinician communication is necessary for successful delegation; (6) coaching helps clinicians understand their patients' barriers to hypertension control; and (7) clinicians would like health coaching to continue on a permanent basis. Clinicians appreciate the presence of nonclinicians on the primary care team. In the coming era of primary care clinician shortage, clinicians can be supportive of nonprofessional team members assisting with the care of patients with hypertension.


[A comparative study of the intracellular regulation of transport ATPase activity in non-nucleated erythrocytes].
Removing the basic cytoskeleton proteins (spectrin, 4.1 and 2.1 band proteins) from the unnuclear erythrocyte membranes of four mammalian species (mouse, hamster, guinea, pig and rabbit) made no changes in Na,K-ATPases, while the specific activity of Ca-ATPases was decreased (the decreasing was of a range of 60-90% depending on the species, in values per mg of protein). The specific activity of the Na,K-ATPase (per ml of cells) varied from 20 to 30% in different species. Incubation of ghosts with erythrocyte haemolysates from rat led to a markedly expressed activation of the Na,K-ATPase in in erythrocytes of all species studied, while the incubation with erythrocyte haemolysate of the same species caused activation of the enzyme in mouse and guinea pig ghosts only. The data obtained support a concept of intracellular Na,K-ATPase activator (probably a protein) having no absolute species specificity. They also show that normal transport function of ATPases in unnuclear erythrocytes needs integrity of the membrane skeleton.


Biliary excretion of colchicine in newborn rats.
The 24-hr LD50 of colchicine in newborn rats is 0.24 mg/kg, which is about 1/10 that observed in the adult. The 24-hr LD50 of colchicine was relatively constant in rats over 25 days of age. In an attempt to determine the mechanism of the increased sensitivity of the newborn rat to the toxic action of colchicine, the distribution of 3H after the administration of 3H-colchicine (0.1 mg/kg) was measured in 10- and 35-day-old rats. The concentration of 3H was higher in all tissues of the newborn than the adult after ip administration, suggesting an immaturity in the pathway for colchicine elimination. After iv administration, radioactivity disappeared much more slowly from the plasma of the newborn rat than from the adult. This was due to a lower capacity of the liver of the newborn to concentrate colchicine and to excrete it into the bile. Development of the hepatic excretory mechanism responsible for excretion of colchicine occurred at the same age as did the increase in LD50. These results suggest that colchicine is more toxic in the newborn because the drug remains in the body for a longer time due to immaturity of the liver excretory process.


The Fungus Beauveria tenella.
Beauveria tenella, an insect pathogen, grows well and sporulates freely in submerged culture. Enzymes that loosened bovine hair that were found in broth cultures were not produced in the presence of chitin, and substitution of peptone broth for peptone-glucose broth did not increase their concentration. Under certain conditions, oxalic acid was the main metabolic product in the peptone medium.


CCi-MOBILE: A Portable Real Time Speech Processing Platform for Cochlear Implant and Hearing Research.
Experimental hardware-research interfaces form a crucial role during developmental stages of any medical, signal-monitoring system as it allows researchers to test and optimize output results before perfecting the design for the actual FDA approved medical device and large-scale production. These testing platforms, intake raw signals through which performance of novel algorithms can be analyzed and modified to generate the desired data points for an optimized output, allowing the advancement of the medical device. With cochlear implants (CIs) and hearing aids (HAs) becoming a more common solution for varying degrees of hearing impairment, having modern signal processing strategies tested for such speech sensitive systems is a necessity. But the rigid design requirements of commercial CI and HA processors make it difficult to explore novel algorithms for research investigations and conducting longitudinal studies. This study presents the design, development, clinical evaluation, and applications of CCi-MOBILE, a computationally powerful signal processing testing platform built for researchers in the hearing-impaired field. The custom-made, portable research platform allows researchers to design and perform complex speech processing algorithm assessment offline and in real-time. It can be operated through user-friendly, open-source software and is compatible with implants manufactured by Cochlear Corporation. The FPGA design and hardware processing pipeline for CI stimulation is discussed followed by results from an acute study with implant users' speech intelligibility in quiet and noisy conditions. The results show a consistent level of performance compared with CI users' clinical processor, thus confirming the viability of the platform in chronic CI based studies.


Effects of bite size and duration of oral processing on retro-nasal aroma release - features contributing to meal termination.
The brain response to a retro-nasally sensed food odour signals the perception of food and it is suggested to be related to satiation. It is hypothesised that consuming food either in multiple small bite sizes or with a longer durations of oral processing may evoke substantial oral processing per gram consumed and an increase in transit time in the oral cavity. This is expected to result in a higher cumulative retro-nasal aroma stimulation, which in turn may lead to increased feelings of satiation and decreased food intake. Using real-time atmospheric pressure chemical ionisation-MS, in vivo retro-nasal aroma release was assessed for twenty-one young, healthy and normal-weight subjects consuming dark chocolate-flavoured custard. Subjects were exposed to both free or fixed bite size (5 and 15 g) and durations of oral processing before swallowing (3 and 9 s) in a cross-over design. For a fixed amount of dark chocolate-flavoured custard, consumption in multiple small bite sizes resulted in a significantly higher cumulative extent of retro-nasal aroma release per gram consumed compared with a smaller amount of large bite sizes. In addition, a longer duration of oral processing tended to result in a higher cumulative extent of retro-nasal aroma release per gram consumed compared with a short duration of oral processing. An interaction effect of bite size and duration of oral processing was not observed. In conclusion, decreasing bite size or increasing duration of oral processing led to a higher cumulative retro-nasal aroma stimulation per gram consumed. Hence, adapting bite size or duration of oral processing indicates that meal termination can be accelerated by increasing the extent of retro-nasal aroma release and, subsequently, the satiation.


Multiplicative neural noise can favor an independent components representation of sensory input.
Arguments have been advanced to support the role of principal components (e.g., Karhunen-Loéve, eigenvector) and independent components transformations in early sensory processing, particularly for color and spatial vision. Although the concept of redundancy reduction has been used to justify a principal components transformation, these transformations per se do not necessarily confer benefits with respect to information transmission in information channels with additive independent identically distributed Gaussian noise. Here, it is shown that when a more realistic source of multiplicative neural noise is present in the information channel, there are quantitative benefits to a principal components or independent components representation for Gaussian and non-Gaussian inputs, respectively. Such a representation can convey a larger quantity of information despite the use of fewer spikes. The nature and extent of this benefit depend primarily on the probability distribution of the inputs and the relative power of the inputs. In the case of Gaussian input, the greater the disparity in power between dimensions, the greater the advantage of a principal components representation. For non-Gaussian input distributions with a kurtosis that is super-Gaussian, an independent components representation is similarly advantageous. This advantage holds even for input distributions with equal power since the resulting density is still rotationally asymmetric. However, sub-Gaussian input distributions can lead to situations where maximally correlated inputs are the most advantageous with respect to transmitting the greatest quantity of information with the fewest number of spikes.


Wafer-scale self-organized InP nanopillars with controlled orientation for photovoltaic devices.
A unique wafer-scale self-organization process for generation of InP nanopillars is demonstrated, which is based on maskless ion-beam etching (IBE) of InP developed to obtain the nanopillars, where the height, shape, and orientation of the nanopillars can be varied by controlling the processing parameters. The fabricated InP nanopillars exhibit broadband suppression of the reflectance, 'black InP,' a property useful for solar cells. The realization of a conformal p-n junction for carrier collection, in the fabricated solar cells, is achieved by a metalorganic vapor phase epitaxy (MOVPE) overgrowth step on the fabricated pillars. The conformal overgrowth retains the broadband anti-reflection property of the InP nanopillars, indicating the feasibility of this technology for solar cells. Surface passivation of the formed InP nanopillars using sulfur-oleylamine solution resulted in improved solar-cell characteristics. An open-circuit voltage of 0.71 V and an increase of 0.13 V compared to the unpassivated device were achieved.


Chemical exposure-response relationship between air pollutants and reactive oxygen species in the human respiratory tract.
Air pollution can cause oxidative stress and adverse health effects such as asthma and other respiratory diseases, but the underlying chemical processes are not well characterized. Here we present chemical exposure-response relations between ambient concentrations of air pollutants and the production rates and concentrations of reactive oxygen species (ROS) in the epithelial lining fluid (ELF) of the human respiratory tract. In highly polluted environments, fine particulate matter (PM2.5) containing redox-active transition metals, quinones, and secondary organic aerosols can increase ROS concentrations in the ELF to levels characteristic for respiratory diseases. Ambient ozone readily saturates the ELF and can enhance oxidative stress by depleting antioxidants and surfactants. Chemical exposure-response relations provide a quantitative basis for assessing the relative importance of specific air pollutants in different regions of the world, showing that aerosol-induced epithelial ROS levels in polluted megacity air can be several orders of magnitude higher than in pristine rainforest air.


Case-Based Questions for Teaching Emergency Medicine Pharmacotherapy.
This pharmacotherapy curriculum is designed for emergency medicine residents of all postgraduate years and could also be given to rotating medical students during clerkships. Curriculum is to run monthly for an 18-month general curriculum cycle. Pharmacotherapy is a critical part of day-to-day practice of Emergency Medicine (EM). The purpose of this innovation is to give this subject specific dedicated instruction time. We introduced a dedicated pharmacotherapy curriculum as part of our conference time through a series of case-based question sets that mirrored our educational blocks. Our goals were to teach residents clinical applications of EM pharmacotherapy including drug selection and consideration of alternatives, interactions, and adverse effects, as well as to prepare them for pharmacotherapy questions on board examinations. The educational strategies used in this curriculum include: case-based vignettes, multiple choice assessments, and guided review explanation and discussion. Questions and explanations are written by resident physicians using a variety of textbooks and online resources and are then reviewed, edited, and expanded upon by attending physicians and an EM pharmacist. This curriculum was implemented in the University of Pittsburgh Emergency Medicine residency program. Curriculum is ongoing and initial data covers a 4-month pilot period. Survey questionnaires were given before and after, using the 7-point Likert scale (1 strongly agree to 7 strongly disagree) for self-assessed knowledge and satisfaction with the curriculum. Primary measure was resident agreement with the statement, "I am confident in overall knowledge of EM pharmacotherapy." We also surveyed readiness for independent practice, knowledge appropriate for training level, board exam preparedness, and satisfaction with curriculum. On the whole residents did feel their pharmacology knowledge improved. Our primary marker was response to a survey question, "I am confident in my overall knowledge of EM pharmacotherapy." In our sample of 30 residents, this question received a pretest score of 3.7 on a 7-point Likert scale (1 strongly agree, 7 strongly disagree). On post intervention surveys this score had improved to 2.6 (p = .00008). In general, residents appreciated this change in curriculum structure. Resident assessment of their improvement during the curriculum was 2.1, aligning with "agree." Satisfaction also improved from a 3.8 on initial survey to a 3.1, with statistical significance (p =.023). We had success in our primary outcome of self-assessed resident learning as above. Satisfaction also improved. Residents assessed self-improvement in knowledge relative to year of training, clinical practice ability, and independent practice ability by statistically significant amounts. In addition, the assessments provided the residency clinical competency committee with objective knowledge of pharmacotherapy-based topics. We feel this easy to implement and effective curriculum would be generalizable across programs looking to add options for teaching EM pharmacotherapy, or to other programs looking to add a formal instruction and evaluation component to traditionally informal curriculum. Emergency Medicine, education, pharmacotherapy, case based, questions, milestones.


Sea-change in reproductive health in emergencies: how systemic improvements to address the MISP were achieved.
The Minimum Initial Services Package (MISP) for reproductive health has been the minimum standard for reproductive health service provision in humanitarian emergencies since 1995. Assessments of acute humanitarian settings in 2004 and 2005 revealed few MISP services in place and low knowledge of the MISP among humanitarian responders. Just 10 years later, assessments of humanitarian settings in 2013 and 2015 found largely consistent availability of MISP services and high awareness of the MISP as a standard among responders. We describe the multi-pronged strategy undertaken by the Women's Refugee Commission and other Inter-agency Working Group on Reproductive Health in Crises (IAWG) member agencies to effect systemic improvements in the availability of the MISP at the onset of humanitarian responses. We find that investments in fact-finding missions, awareness-raising, capacity development, policy harmonisation, targeted funding, emergency risk management, and community resilience-building have been critical to facilitating a sea-change in reproductive health responses in acute, large-scale emergencies. Efforts were underpinned by collaborative, inter-agency partnerships in which organisations were committed to working together to achieve shared goals. The strategies, activities, and achievements contain valuable lessons for the health sector, including reproductive health, and other sectors seeking to better integrate emerging or marginalised issues into humanitarian action.


Bioinspired nanoreactors for the biomineralisation of metallic-based nanoparticles for nanomedicine.
This review explores the synthesis of inorganic metallic-based nanoparticles (MBNPs) (metals, alloys, metal oxides) using biological and biologically inspired nanoreactors for precipitation/crystallisation. Such nanoparticles exhibit a range of nanoscale properties such as surface plasmon resonance (nobel metals e.g. Au), fluorescence (semiconductor quantum dots e.g. CdSe) and nanomagnetism (magnetic alloys e.g. CoPt and iron oxides e.g. magnetite), which are currently the subject of intensive research for their applicability in diagnostic and therapeutic nanomedicine. For such applications, MBNPs are required to be biocompatible, of a precise size and shape for a consistent signal or output and be easily modified with biomolecules for applications. Ideally the MBNPs would be obtained via an environmentally-friendly synthetic route. A biological or biologically inspired nanoreactor synthesis of MBNPs is shown to address these issues. Biological nanoreactors for crystallizing MBNPs within cells (magnetosomes), protein cages (ferritin) and virus capsids (cowpea chlorotic mottle, cowpea mosaic and tobacco mosaic viruses), are discussed along with how these have been modified for applications and for the next generation of new materials. Biomimetic liposome, polymersome and even designed self-assembled proteinosome nanoreactors are also reviewed for MBNP crystallisation and further modification for applications. With the advent of synthetic biology, the research and understanding in this field is growing, with the goal of realising nanoreactor synthesis of MBNPs for biomedical applications within our grasp in the near future.


Memory monitoring and memory control in chronic stroke patients Dissociated processes.
Memory problems are common in stroke patients, although little is known about how accurately chronic stroke patients can monitor and control memory processes. The performance of memory and metamemory in stroke patients and healthy controls were investigated, as well as dissociation between performances. 10 adults with right hemisphere lesion (mean [M] age=53.2 [SD=9.7]), 10 with left hemisphere lesion (M age=60.4 [SD=6.6]) and 20 healthy participants (M age=56.5 [SD=9.3] with no neurological disease, matched for sex, age and years of education participated in a multiple-case design study. Participants completed a metamemory experimental paradigm, as well as immediate and delayed word recall and recognition tasks. Data indicated that 10 out of the 20 patients presented significantly lower scores compared to controls, two of which had global deficits (functional association). Functional dissociations between memory monitoring (judgments of learning, JOL), control (allocation of study time) and capacity (cued-recall task) among patients were found for eight cases, suggesting these processes are independent. These findings reveal stroke patients may have specific metamemory impairment and can contribute to the understanding of cognitive models of metamemory processing.


Ethanol inhibits excitatory neurotransmission in the nucleus accumbens of adolescent mice through GABAA and GABAB receptors.
Age-related differences in various acute physiological and behavioral effects of alcohol have been demonstrated in humans and in other species. Adolescents are more sensitive to positive reinforcing properties of alcohol than adults, but the cellular mechanisms that underlie such a difference are not clearly established. We, therefore, assessed age differences in the ability of ethanol to modulate glutamatergic synaptic transmission in the mouse nucleus accumbens (NAc), a brain region importantly involved in reward mechanisms. We measured field excitatory postsynaptic potentials/population spikes (fEPSP/PS) in NAc slices from adolescent (22-30 days old) and adult (5-8 months old) male mice. We found that 50mM ethanol applied in the perfusion solution inhibits glutamatergic neurotransmission in the NAc of adolescent, but not adult, mice. This effect is blocked by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline and by the GABAB receptor antagonist CGP 55845. Furthermore, bicuculline applied alone produces a stronger increase in the fEPSP/PS amplitude in adult mice than in adolescent mice. Activation of GABAA receptors with muscimol produces a stronger and longer lasting depression of neurotransmission in adolescent mice as compared with adult mice. Activation of GABAB receptors with SKF 97541 also depresses neurotransmission more strongly in adolescent than in adult mice. These results demonstrate that an increased GABA receptor function associated with a reduced inhibitory tone underlies the depressant action of ethanol on glutamatergic neurotransmission in the NAc of adolescent mice.


A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers who receive adjuvant chemotherapy following surgery.
The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate triple negative breast cancers (TNBCs) among patients, who received adjuvant chemotherapy after curative surgery. We tested whether the results of a NanoString expression assay that targeted 250 prospectively selected genes and used mRNA extracted from formalin-fixed, paraffin-embedded would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high). NanoString expression profiles were obtained for 203 tumor tissue blocks. Increased expressions of the five genes (SMAD2, HRAS, KRT6A, TP63 and ETV6) and decreased expression of the two genes (NFKB1 and MDM4) were associated favorable prognosis and were validated with cross-validation. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low- and high-risk groups according to gene expression signature were 62% [95% confidence interval (CI), 48.6-78.9%] and 85% (95% CI, 79.2-90.7%), respectively. When adjusting for TNM stage, the distant recurrence-free survival (DRFS)s in the low-risk group was significantly longer than that in the high-risk group (p <0.001) for early stage (I and II) and advanced stage (III) tumors. In a multivariate Cox regression model, the gene expression signature provided significant predictive power jointly with the TNM staging system. A seven-gene signature could be used as a prognostic model to predict DRFS in patients with TNBC who received curative surgery followed by adjuvant chemotherapy.


Immunization of mice with Yersinia enterocolitica leads to the induction of antithyrotropin receptor antibodies.
It is well established that autoimmune Graves' disease, which is characterized by hyperthyroidism, is mediated by autoantibodies to the thyrotropin receptor (TSHr). Although what initially triggers this autoantibody response is not known, a number of studies have suggested that Yersinia enterocolitica, an enterobacteria, could initiate the immune response against the TSHr. In this study, we produced antibodies against purified extracellular domain of human TSHr (ETSHr) and showed that anti-ETSHr antibodies reacted with envelope preparations from Y. enterocolitica. This reactivity was specifically blocked by preincubating sera with purified ETSHr. Moreover, antibodies reactive with ETSHr were induced by immunizing mice with Y. enterocolitica but not with Shigella flexneri SA100, Salmonella typhimurium TML, and Listeria monocytogenes. Anti-Y. enterocolitica antisera specifically reacted with the ETSHr protein and the reactivity could be blocked both by ETSHr and Y. enterocolitica envelope proteins. Our studies provide the first direct evidence that immunization with Y. enterocolitica can lead to the production of antibodies capable of reacting with TSHr and might provide the initial stimulus necessary for breakdown of self-tolerance to TSHr, eventually leading to the development of autoimmunity to TSHr.


2-Methoxyestradiol-bis-sulphamate refrains from inducing apoptosis and autophagy in a non-tumorigenic breast cell line.
Anticancer research resulted in the discovery of a promising antimitotic metabolite, 2-methoxyestradiol. 2-Methoxyestradiol-bis-sulphamate, a bis-sulphamoylated analogue exerts antiproliferative- and antimitotic activity. Investigating the anticancer potential of 2-methoxyestradiol-bis-sulphamate requires demonstrating the influence of 2-methoxyestradiol-bis-sulphamate on non-tumorigenic cells. This project focused on the in vitro effects of 2-methoxyestradiol-bis-sulphamate on the non-tumorigenic MCF-12A breast epithelial cell line. The in vitro influence of 2-methoxyestradiol-bis-sulphamate was investigated on cell cycle progression, possible induction of apoptosis and autophagy and reactive oxygen species generation. Cell cycle progression was done using flow cytometry in conjunction with ethanol fixation and propidium iodide staining. Displaying effects on the mitochondrial membrane potential was achieved utilizing flow cytometry and the MitoCapture TM Mitochondrial apoptosis detection kit. Autophagy detection was done by means of flow cytometry and anti-LC3B conjugated to DyLight 488. Reactive oxygen species generation was conducted employing flow cytometry and 2,7-dichlorofluorescein diacetate and hydroethidine. This study demonstrated that 2-methoxyestradiol-bis-sulphamate did not affect cell cycle progression or reactive oxygen species in a statistically significant manner in the non-tumorigenic MCF-12A cell line. In addition, 2-methoxyestradiol-bis-sulphamate did not statistically significantly induce apoptosis or autophagy. Reports indicate that 2-methoxyestradiol-bis-sulphamate induces apoptosis and autophagy in several tumorigenic cell lines. The anticancer ability of 2-methoxyestradiol-bis-sulphamate is due to its antimitotic activity. However, this study demonstrates the promising notion that 2-methoxyestradiol-bis-sulphamate does not affect the non-tumorigenic MCF-12A cells. This project contributes to the embedded scientific knowledge regarding the differential death mechanisms used by 2-methoxyestradiol-bis-sulphamate on tumorigenic and non-tumorigenic cell lines.


Separation of rabbit mammary-gland prolactin receptors by ion-exchange chromatography, h.p.l.c.-gel filtration and ultracentrifugation.
Rabbit mammary-gland prolactin (Prl) receptors in the microsomal fraction were solubilized in 7.5 mM-Chaps) or 1% Triton X-100 and analysed by ion-exchange chromatography using DEAE-Bio-Gel A. Prl receptors in the presence of 7.5 mM-Chaps were separated into two different fractions (Fr. A and B), both of which showed identical specificity of binding to peptide hormones as those in the Chaps or Triton extract. oPrl and human growth hormone (hGH) bound to the same site, but other non-lactogenic hormones (follicle-stimulating hormone, oGH, luteinizing hormone and insulin) failed to bind to the Prl receptors. The dissociation constant (Kd) for Prl binding to the receptors in Fr. A was about 50% of those in Fr. B, suggesting that the rabbit mammary gland contains two types of Prl receptors, one with a high, and one with a low, Kd for Prl binding. A decrease in the concentration of Chaps in the column buffer to 4 mM caused aggregation of the receptors in Fr. A. H.p.l.c.-gel filtration, using Shim pack 150 and 300 columns connected in series, separated the receptor as a protein with an Mr of 74,000 +/- 4,900 (mean +/- S.D.) in the presence of 5 mM-Chaps, or of 36,800 +/- 2,100 in the presence of 7.5 mM-Chaps. Sucrose-gradient-centrifugation analysis showed that the Prl-receptor complexes in the presence of 5 mM-Chaps were sedimented between gamma-globulin and bovine serum albumin (5.56 +/- 0.22 S). As the Chaps concentration was increased to 7.5 mM, a further peak of the Prl-receptor complexes (4.01 +/- 0.23 S) appeared below ovalbumin. The present data suggest that the binding subunit causes the monomeric subunit to aggregate with itself or with another specific associated protein of similar Mr.


The community health clinics as a learning context for student nurses.
The purpose of the research study was to describe guidelines to improve the community health clinics as a learning context conductive to learning. The objectives of the study commenced by getting the perception of student nurses from a nursing college in Gauteng; community sisters from ten community health clinics in the Southern Metropolitan Local Council and college tutors from a college in Gauteng. The research design and method used, consisting of a qualitative, exploratory, descriptive and contextual approach and the design was divided into two phases. Phase one consisted of a field/empirical study and phase two of conceptualization. In all the samples follow-up focus group interviews were conducted to confirm the findings. To ensure trustworthiness, Lincoln and Guba's model (1985) was implemented and data analysis was according to Tesch's model (1990 in Creswell 1994:155) based on a qualitative approach. The conceptual framework discussed, indicating a body of knowledge, was based on the study and empirical findings from phase one to give clear meaning and understanding regarding the research study.


-173G/C polymorphism in the promoter of MIF is associated with hepatitis B virus infection in a Chinese Han population.
In addition to the host immune response, genetic and environmental factors play crucial roles in the manifestation of hepatitis B virus (HBV) infection. The macrophage migration inhibitory factor (MIF) -173G/C polymorphism (rs755622), located in the promoter region of MIF, may play integral roles in diverse processes, including the immune response. Thus, the MIF -173G/C polymorphism may influence the immune response to HBV during natural infection. We investigated whether the MIF -173G/C polymorphism was associated with susceptibility to HBV infection in a Chinese Han population. A total of 596 HBV infection cases and 612 age-matched controls were recruited for the study. Genotyping of the MIF -173G/C polymorphism was performed using the allele-specific polymerase chain reaction method. The frequencies of the alleles and genotypes in patients and controls were compared using the χ(2) test. Carriers of the variant C allele in MIF -173 G/C were at significantly higher risk of HBV infection than carriers of the wild-type allele (P = 0.032, odds ratio = 0.799, 95% confidence interval = 0.651-0.981). However, there was no significant difference in the distribution of MIF -173G/C genotypes between case and control groups in either population (P = 0.096, degrees of freedom = 2). Our findings indicate that the G to C base change in MIF -173 G/C confers an increased risk of development of HBV infection by altering the expression of MIF in our Chinese Han population.


Target therapy in HER2-overexpressing breast cancer patients.
The development of new therapeutic strategies, such as monoclonal antibodies directed against human epidermal growth factor receptor-2 (HER2), has offered new hopes for women with early breast cancer whose tumors overexpress HER2. We retrospectively analyzed the population-based data of Breast Cancer Registry of Palermo in 2004-2006, and selected 1401 invasive breast cancer cases, nonmetastatic at diagnosis, having HER2/neu oncogene expression determined. We have correlated this information to age, tumor stage at diagnosis (TNM), nodal involvement, and receptor status (ER and PgR). Survival analysis was conducted dividing the patients in two different groups according to date of diagnosis: one group diagnosed in 2004 and a second group in 2005-2006. In the 460 cases of 2004, nodal involvement, receptor status, age at diagnosis and TNM maintained a strong predictive value (p < 0.0001). In this group of patients, overall survival was significantly different according to the HER2 expression levels (p = 0.001). In the second group of patients (941 incident cases in 2005-2006) there was a statistically significant survival difference comparing patients with high levels of HER2 expression treated with trastuzumab versus those untreated (p = 0.006). Our data show that elevated levels of HER2 are a negative prognostic factor. In addition, patients overexpressing HER2 show a significant increase of overall survival when treated with trastuzumab.


Bacterial wall lipopolysaccharide as a cause of intussusception in mice.
There is evidence that intussusception is associated with bacterial infection. It was hypothesized that a component of the bacterial wall may induce the intussusception. This study was intended to determine whether lipopolysaccharide from Escherichia coli or Salmonella can initiate intussusception in mice. Lipopolysaccharide was injected intraperitoneally in mice, and the animals were examined for the presence of intussusception from 2 to 192 hours after injection. Gastrointestinal transit was assessed by measuring the passage of charcoal in the small intestine. Transit index was defined as the ratio between the distance traveled by charcoal and the total length of the small intestine. Intussusceptions were found in as much as 25.9% of lipopolysaccharide-injected animals, whereas in control animals, the incidence was zero. The threshold for the lipopolysaccharide effect was at 4 mg/kg and incidence reached a plateau at 8 mg/kg to 16 mg/kg. The incidence of intussusception peaked 6 hours after injection of lipopolysaccharide and declined to zero after 15 hours. To test the possibility that lipopolysaccharide induces intussusception by altering motility, its effect on transit index was measured. A dose of 12 mg/kg lipopolysaccharide reduced the transit index from 56.2+/-1.4% to 37.7+/-2.1% (p < 0.05). No microscopic histologic changes were found in the bowels with intussusception. Intraperitoneal bacterial wall lipopolysaccharide causes intussusception in mice by disturbing gastrointestinal motility.


[Pericardial involvement in leukemia and malignant lymphoma].
Pericardial exudate and/or spread of the tumour to the pericardium occurs frequently in leukaemia and malignant lymphomata. Metastases to the pericardium may be demonstrated at autopsy in 50% and 20-25%, respectively. In the majority of cases no symptoms from the heart occur. In cases with significant pericardial effusion or constrictive pericarditis, urgent treatment is indicated. Pericardiocentesis is carried out in cases of cardiac tamponade. Irradiation has frequently a rapid and dramatic effect in cases of massive tumour infiltration in the pericardium. Long-term treatment depends on the malignant haematological disease concerned. Meticulous diagnostic investigation is therefore indicated in every case with cardiac symptoms. This has frequently therapeutic consequences, reduces the morbidity and prolongs survival. Two cases of acute pericardial effusion with haemodynamic consequences are reviewed in this article. The haematological diagnoses were acute myeloid leukaemia and malignant lymphoma (diffuse large-cell non-Hodgkin's lymphoma), respectively.


The copper/caeruloplasmin ratio in routine clinical practice in different laboratories.
The diagnosis of copper deficiency and excess states is challenging. It was hoped that the non-caeruloplasmin-bound ("free") copper would reduce this difficulty; however, it has its own problems. The copper/caeruloplasmin ratio has been advocated as an alternative index of copper status, especially as it would not need gender-derived or age-derived reference intervals. However, there are no comparative data for different populations using different assays. Independent paired copper and caeruloplasmin data were retrospectively obtained for three laboratories. From these data, the copper/caeruloplasmin ratio was calculated, and descriptive statistics for the populations and methods were obtained. The relationship between the copper/caeruloplasmin ratio and both copper and caeruloplasmin were also investigated for the three laboratories. All three datasets displayed a non-Gaussian distribution. The Burton median was statistically different from the two other medians, which did not differ significantly from each other. The regression lines for both copper and caeruloplasmin with the ratio differed from each other. The copper/caeruloplasmin ratio behaves differently depending on the laboratory, the population studied, or both. Thus, cut-offs in the literature are not transferable. Each laboratory should therefore derive its own cut-offs.


Spatio-structural granularity of biological material entities.
With the continuously increasing demands on knowledge- and data-management that databases have to meet, ontologies and the theories of granularity they use become more and more important. Unfortunately, currently used theories and schemes of granularity unnecessarily limit the performance of ontologies due to two shortcomings: (i) they do not allow the integration of multiple granularity perspectives into one granularity framework; (ii) they are not applicable to cumulative-constitutively organized material entities, which cover most of the biomedical material entities. The above mentioned shortcomings are responsible for the major inconsistencies in currently used spatio-structural granularity schemes. By using the Basic Formal Ontology (BFO) as a top-level ontology and Keet's general theory of granularity, a granularity framework is presented that is applicable to cumulative-constitutively organized material entities. It provides a scheme for granulating complex material entities into their constitutive and regional parts by integrating various compositional and spatial granularity perspectives. Within a scale dependent resolution perspective, it even allows distinguishing different types of representations of the same material entity. Within other scale dependent perspectives, which are based on specific types of measurements (e.g. weight, volume, etc.), the possibility of organizing instances of material entities independent of their parthood relations and only according to increasing measures is provided as well. All granularity perspectives are connected to one another through overcrossing granularity levels, together forming an integrated whole that uses the compositional object perspective as an integrating backbone. This granularity framework allows to consistently assign structural granularity values to all different types of material entities. The here presented framework provides a spatio-structural granularity framework for all domain reference ontologies that model cumulative-constitutively organized material entities. With its multi-perspectives approach it allows querying an ontology stored in a database at one's own desired different levels of detail: The contents of a database can be organized according to diverse granularity perspectives, which in their turn provide different views on its content (i.e. data, knowledge), each organized into different levels of detail.


Individual and community factors contributing to anemia among women in rural Baja California, Mexico.
Anemia is a public health concern among women in rural Baja California, Mexico. The purpose of this study was to identify the individual and community factors contributing to the disproportionately high prevalence of anemia among women in this region. A cross-sectional study of 118 women (15-49 years) was performed in a rural colonia (small settlement) in Baja California, Mexico in 2012. Participants completed a survey comprised of demographic, socioeconomic, health, and dietary questions and provided a capillary blood sample. A portable HemoCue was used to measure hemoglobin and diagnose anemia. Anemic participants provided a venous blood sample for laboratory testing to elucidate the etiology of anemia. Anemic participants received vitamin supplements and nutritional counseling. Assessments of six local tiendas (community grocery stores) were performed to ascertain the types of food available for purchase within the community. Prevalence of anemia was 22% among women; laboratory tests revealed iron deficiency was the primary etiology in 80.8% of anemia cases. Other causes of anemia in women included vitamin B-12 deficiency (11.5%) and combined iron and vitamin B-12 deficiency (7.7%). Women from low SES households and women enrolled in the government assistance program Prospera were significantly more likely to be anemic (OR = 3.48, 95% CI 1.35-8.98 and OR = 2.49, 95% CI 1.02-6.09, respectively). Vitamin supplementation was significantly more common among non-anemic women (OR = 0.12, 95% CI 0.02-0.94). Dietary assessments showed limited consumption of iron absorption enhancing foods such as fruits and vegetables. Assessments of local tiendas revealed at least one type of meat and citrus fruit available for purchase at each store; however, leafy green vegetables were only available for purchase at one store. All cases of anemia were due to nutritional deficiencies. While vitamin supplementation is a temporary solution, improved individual nutrition knowledge and community access to iron absorption enhancing foods, particularly produce, is needed. Promoting government assistance programs like Prospera and implementing additional programs designed to improve nutrition and health literacy, in conjunction with ensuring access to nutritious foods, might reduce the high prevalence nutritional anemia within the community.


Pod1 induces myofibroblast differentiation in mesenchymal progenitor cells from mouse kidney.
The class II basic helix-loop-helix (bHLH) transcription factor Pod1 is expressed in mesenchymal cells including smooth muscle progenitors during development and in interstitial cells in adult organs. To determine the role of Pod1 in mesenchymal cell smooth muscle and myofibroblast differentiation, we examined a kidney progenitor cell line (4E) that endogenously expresses Pod1 and its class I bHLH partner E2A. In vitro-translated Pod1 co-immunoprecipitated E2A and increased E2A binding to a calponin promoter E-box sequence as determined by an electrophoresis mobility shift assay (EMSA). Overexpression of Pod1 and E2A resulted in increased smooth muscle and myofibroblast gene expression including calponin, SM22alpha, alphaSMA, fibronectin, and connective tissue growth factor (CTGF) compared with overexpression of E2A alone. Suppression of Pod1 by siRNA resulted in increased cell proliferation and reduced expression of alphaSMA, fibronectin, and CTGF, and myofibroblast secreted proteins including pro-fibrotic cytokines and inhibitors of matrix metalloproteinases. Examination of the signaling pathways for myofibroblast differentiation including Rho/Rho kinase and p38 MAPK showed that inhibition of actin polymerization by Rho kinase inhibitors decreased nuclear Pod1 levels while inhibition of p38 MAPK decreased Pod1 expression. These results indicate that Pod1 increases myofibroblast differentiation in combination with E2A and promotes a myofibroblast phenotype in mesenchymal progenitor cells.


Thermal stability of Mg/Co multilayer with B4C, Mo or Zr diffusion barrier layers.
The efficiency of B(4)C, Mo and Zr barrier layers to improve thermal stability of Mg/Co multilayer up to 400 °C is investigated. Multilayers were deposited by direct current magnetron sputtering and characterized using X-ray and extreme ultraviolet reflection. The results suggest that B(4)C barrier layer is not effective due to drastic diffusion at Mg-B(4)C interface. Although introducing Mo barriers improves the thermal stability from 200 to 300 °C, it increases the interface roughness and thus degrades the optical performances. On the contrary, Zr barriers can significantly increase the thermal stability of Mg/Co up to 400 °C without optical performance degradation. Thus, Mg/Zr/Co/Zr is suitable for EUV applications requiring both optimal optical performances and heat resistance.


Nanocluster formation and stabilization fundamental studies: ranking commonly employed anionic stabilizers via the development, then application, of five comparative criteria.
To start, a brief introduction is provided on the importance of transition-metal nanoclusters, on the need to develop and then apply methods to rank the nanocluster formation and then stabilizing abilities of commonly employed anions, solvents, cations, and polymers, and on the somewhat confused literature of nanocluster stabilization. The fundamental importance of surface-adsorbed anions in transition-metal nanocluster stabilization is noted, the reason the present studies begin with a study of nanocluster-stabilizing anions. Next, five criteria, as well as the associated experimental methods, are developed to evaluate the efficacy of nanocluster stabilizing agents. The criteria are of fundamental significance in that they allow the separation of stabilizing agent effects on nanocluster formation from those on nanocluster stabilization. The results from applying the five criteria to four commonly employed anions lead to the first "anion series" of relative nanocluster-formation and stabilizing abilities, at least for the Ir(0) nanoclusters examined and by the following five criteria: [(P(2)W(15)Nb(3)O(61))(2)O](16-) (a Brphinsted-basic polyoxoanion) > C(6)H(5)O(7)(3-) (citrate trianion) > [-CH(2)-CH(CO(2))-](n)(n-) (polyacrylate) approximately Cl(-). In addition to the needed methods and the first anion series, six other (8 total) conclusions are reached, important insights in an area previously lacking hard information about which anions are the better choices for nanocluster formation and stabilization. The results are also of significance in establishing polyoxoanions, notably highly charged and basic polyoxoanions such as [(P(2)W(15)Nb(3)O(61))(2)O](16)(-), as the present "Gold Standards" among currently known nanocluster stabilizing anions, and according to the above five criteria. Such standards provide a reference point for future work aspiring to develop even better nanocluster stabilizing anions, solvents, cations, and polymers or their combinations.


Stress response and adaptation: a new molecular toolkit for the 21st century.
Much research in comparative biochemistry is focused on understanding the molecular mechanisms that allow organisms to adapt to and survive diverse environmental challenges. In recent years, genomic and proteomic approaches have been key drivers of advancement in the field, for example, providing knowledge about gene and protein expression, regulation of signal transduction pathways, and functional control of enzymes/proteins by reversible protein phosphorylation. Advances in comparative biochemistry have always drawn upon conceptual and technological advances that arise from "mainline" biochemistry and molecular biology, often from medical models. The present article discusses three such advances that will have major impacts on comparative biochemistry in the 21st century. The first is the crucial role of posttranslational modification in metabolic control, expanding outwards from reversible phosphorylation to explore the individual and interacting effects of protein modification by acetylation, methylation, SUMOylation and O-GlcNAcylation, among others. The second is the newly recognized role of non-coding RNA in the regulation of gene expression, particularly the action of microRNAs. The third is the emergence of powerful multiplex technology that allows rapid, high-throughput detection of analytes and will revolutionize RNA and protein profiling in the comparative biochemistry laboratory. Commercial tools such as Luminex allow researchers to simultaneously quantify up to 100 different analytes in a single sample, thereby creating broad functional analyses of metabolism and cell signaling pathways.


The elusive transporters with a high affinity for glutamate.
Removal of glutamate from the synaptic cleft is an essential component of the transmission process at glutamatergic synapses. This requirement is fulfilled by transporters that have a high affinity for glutamate and exhibit a unique coupling to Na+, K+ and OH- ions. Independently, three groups have succeeded in cloning cDNAs encoding high-affinity Na(+)-dependent glutamate transporters. These transporters are structurally distinct from previously characterized neurotransmitter transporters and show sequence identity with prokaryotic glutamate and dicarboxylate transporters. In addition, they exhibit significant differences in their structure, function and tissue distribution. This review compares and contrasts these differences, and incorporates into the existing body of knowledge these new breakthroughs.


Problems identified by secondary review of accepted manuscripts.
To test the hypothesis that no important deficits would be identified on further review of accepted manuscripts, and that such manuscripts would be recommended for publication on rereview, we sent manuscripts that had been accepted for publication, after review and revision, for rereview by new referees who were unaware of the status of the manuscripts. Each review was evaluated independently by two assistant editors to determine whether substantive criticisms were identified by the new reviewers. The majority of manuscripts were thought by the new reviewers to have defects that warranted further revision, but the problems noted were often dissimilar. However, 80% of the manuscripts were recommended for publication and others were judged suitable for publication, although not at a high priority. The assistant editors frequently differed in their judgments whether a given criticism of a reviewer warranted further revision; nevertheless, there was infrequent disagreement regarding the basic decision for acceptance or rejection.


Swearing as a response to pain: A cross-cultural comparison of British and Japanese participants.
Research suggests swearing can moderate pain perception. The present study assessed whether changes in pain perception due to swearing reflect a "scripting" effect by comparing swearing as a response to pain in native English and Japanese speakers. Cognitive psychology denotes a 'script' to be a sequence of learnt behaviours expected for given situations. Japanese participants were included as they rarely, if ever, swear as a response to pain and therefore do not possess an available script for swearing in the context of pain. It was hypothesised that Japanese participants would demonstrate less tolerance and more sensitivity to pain than English participants, and - due to a lack of an available script of swearing in response to pain - that Japanese participants would not experience swearword mediated hypoalgesia. Fifty-six native English (mean age=23 years) and 39 Japanese (mean age=21) speakers completed a cold-pressor task whilst repeating either a swear on control word. A 2 (culture; Japanese, British)×2 (word; swear; non-swear) design explored whether Japanese participants showed the same increase in pain tolerance and experienced similar levels of perceived pain when a swearing intervention was used as British participants. Pain tolerance was assessed by the number of seconds participants could endure of cold-pressor exposure and self-report pain measurements. Levels of perceived pain were assessed using a 120-mm horizontal visual analogue scale anchored by descriptors in the participant's native language of "no pain" (left) and "terrible pain" (right). The participant was asked to mark a 10mm vertical line to indicate overall pain intensity. The score was measured from the zero anchor to the participant's mark. Japanese participants reported higher levels of pain (p<0.005) and displayed lower pain tolerance than British participants (p<0.05). Pain tolerance increased in swearers regardless of cultural background (p<0.001) and no interaction was found between word group and culture (p=0.96), thereby suggesting that swearing had no differential effect related to the cultural group of the participant. The results replicate previous findings that swearing increases pain tolerance and that individuals from an Asian ethnic background experience greater levels of perceived pain than those from a Caucasian ethnic background. However, these results do not support the idea of pain perception modification due to a "scripting" effect. This is evidenced as swearword mediated hypoalgesia occurs irrespective of participant cultural background. Rather, it is suggested that modulation of pain perception may occur through activation of descending inhibitory neural pain mechanisms. As swearing can increase pain tolerance in both Japanese and British people, it may be suggested that swearword mediated hypoalgesia is a universal phenomenon that transcends socio-cultural learnt behaviours. Furthermore, swearing could be encouraged as an intervention to help people cope with acute painful stimuli.


Duodenal and ileal nutrient deliveries regulate human intestinal motor and pancreatic responses to a meal.
It is assumed that in humans pancreatic and gastrointestinal motor responses to a meal are coordinated and regulated mainly by duodenal nutrient exposure. On the other hand, there is evidence that the distal intestine may participate in the regulation of gastrointestinal functions. The aim of this study was to compare human pancreatic and intestinal motility responses to a meal and to correlate them with nutrient exposure of the proximal and distal intestine. After intubation with an oroileal multilumen tube for marker perfusion, duodenal and ileal aspiration, and intestinal manometry, 14 healthy subjects received a mixed test meal (1,257 kJ). Intraluminal nutrient concentrations, enzyme activities, and small intestinal motility were analyzed for 6 h postprandially. Duration of duodenal nutrient exposure was 3.4 +/- 0.2 h, and duration of pancreatic enzyme response and fed motor pattern was 2.5 +/- 0.2 and 3.5 +/- 0.3 h, respectively. Durations of pancreatic secretory and motor responses were correlated (P < 0.05), but neither duration of digestive secretory nor of motor activity correlated with that of prandial duodenal nutrient concentrations. By contrast, they were associated with the relative increase in ileal nutrient delivery late postprandially (P < 0.05). Physiological late postprandial delivery of nutrients to distal intestinal sites is correlated with the termination of digestive pancreatic and motor responses and may participate in their control.


TempliPhi: A sequencing template preparation procedure that eliminates overnight cultures and DNA purification.
Preparing plasmid templates for DNA sequencing is the most time-consuming step in the sequencing process. Current template preparation methods rely on a labor-intensive, multistep procedure that takes up to 24 h and produces templates of varying quality and quantity. The TempliPhi DNA Sequencing Template Amplification Kit eliminates the requirement for extended bacterial growth prior to sequencing and saves laboratory personnel hands-on time by eliminating the centrifugation and transfer steps currently required by older preparatory methods. In addition, costly purification filters and columns are not necessary, as amplified product can be added directly to a sequencing reaction. Starting material can be any circular template from a colony, culture, glycerol stock, or plaque. Based on rolling circle amplification and employing bacteriophage Phi29 DNA polymerase, the method can produce 3-5 microg of template directly from a single bacterial colony in as little as 4 h. Implementation of these procedures in a laboratory or core sequencing facility can decrease cost on tips, plates, and other plasticware, while at the same time increase throughput.


Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs.
Primitive hematopoietic stem cells are closely associated with discrete in vivo microenvironments. These "niches" are thought to provide the molecular signals that mediate stem cell differentiation and self-renewal. We have dissected the fetal liver microenvironment into distinct cellular components by establishing an extensive panel of stromal cell lines. One particular cell line maintains repopulating stem cells for prolonged in vitro culture periods. A subtraction cloning strategy has yielded a cDNA that encodes a cell surface glycoprotein with a restricted pattern of expression among stromal cell lines. This molecule, previously identified as delta-like/preadipocyte factor-1, contains epidermal growth factor-like repeats that are related to those in the notch/delta/serrate family of proteins. We have investigated the potential role of this molecule in hematopoietic stem/progenitor cell regulation. We show that the delta-like protein displays activity on purified stem cells by promoting the formation of "cobblestone areas" of proliferation. These cobblestone areas contain both primitive high-proliferative potential progenitors and in vivo repopulating stem cells.


Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea.
Clostridium difficile-associated disease (CDAD) is the major known cause of antibiotic-induced diarrhea and colitis, and the disease is thought to result from persistent disruption of commensal gut microbiota. Bacteriotherapy by way of fecal transplantation can be used to treat recurrent CDAD, which is thought to reestablish the normal colonic microflora. However, limitations of conventional microbiologic techniques have, until recently, precluded testing of this idea. In this study, we used terminal-restriction fragment length polymorphism and 16S rRNA gene sequencing approaches to characterize the bacterial composition of the colonic microflora in a patient suffering from recurrent CDAD before and after treatment by fecal transplantation from a healthy donor. Although the patient's residual colonic microbiota, prior to therapy was deficient in members of the bacterial divisions-Firmicutes and Bacteriodetes, transplantation had a dramatic impact on the composition of the patient's gut microbiota. By 14 days posttransplantation, the fecal bacterial composition of the recipient was highly similar to that of the donor and was dominated by Bacteroides spp. strains and an uncharacterized butyrate producing bacterium. The change in bacterial composition was accompanied by resolution of the patient's symptoms. The striking similarity of the recipient's and donor's intestinal microbiota following after bacteriotherapy suggests that the donor's bacteria quickly occupied their requisite niches resulting in restoration of both the structure and function of the microbial communities present.


A survey of atrial fibrillation in general practice: the West Birmingham Atrial Fibrillation Project.
The management of atrial fibrillation (AF) has changed substantially in recent years, especially with a greater appreciation of the prophylactic role of antithrombotic therapy against stroke. There is therefore a need for further information on the prevalence of AF in Britain, the prevalence of (and contraindications to) anticoagulant treatment, and the factors that influence doctors' decisions in treating AF, including the investigation of patients with this arrhythmia. To investigate the prevalence, clinical features and management of patients with AF in a general practice setting. Cross-sectional survey of patients using treatment prescriptions and clinical records in two general practices from the west of Birmingham (serving a patient population of 16,519) where 4522 subjects (27.4%) were aged > or = 50 years. One hundred and eleven (2.4%) patients who were aged > or = 50 years were found to be in AF (42 males; mean age 76.6, SD 9.1); 77.5% were Caucasian, 2.7% Afro-Caribbean, 0.9% Asian, and 0.9% mixed race; in 20 cases there was no information on ethnicity. Of the AF patients, 5.4% were aged 50-60 years, 16.2% aged 61-70 years, 20.7% aged 71-75 years, 20.7% aged 76-80 years, 24.3% aged 81-85 years, and 12.6% aged > 85 years old, with female patients being significantly older than males. Eighty-one patients (73%) had chronic AF, while 30 patients (27%) had paroxysmal AF. The most common associated factors were hypertension (36.9%) and ischaemic heart disease (28.8%), with no obvious cause for AF in six patients. Cardiac failure was associated with AF in 34 patients (30.6%), and stroke had occurred in 29 patients (18%). Only 20 patients (18%) had had an echocardiogram, 26 (23.4%) a chest X-ray, and 58 (52.3%) thyroid function test. Only 30.6% had ever presented to hospital practice. Warfarin was prescribed to 40 patients (36%), with anticoagulation intensity monitoring by the general practitioner (GP) in three cases (7.5%), by a hospital clinic in 30 (75%), and by both GP and hospital in seven cases (17.5%). Of those not anticoagulated (n = 71), only 12 patients (16.9%) had contraindications to warfarin therapy. Patients treated with warfarin were younger than those who were not prescribed warfarin (71.3 versus 79.6 years, P < 0.001). Aspirin was being prescribed for 21 patients (18.9%), primarily for previous myocardial infarction. Only five patients (4.5%) had ever had attempted cardioversion. Atrial fibrillation is a common arrhythmia in general practice, and is commonly associated with hypertension, ischaemic heart disease and heart failure. There is a suboptimal application of standard investigations and use of antithrombotic therapy or attempted cardioversion; and few patients have presented to hospital practice. Guidelines on the management of this common arrhythmia in general practice are required.


Apraxic agraphia with neglect-induced paragraphia.
Agraphia may result from the loss or unavailability of the memory of movements necessary to form written letters. For this mechanism to be invoked, it must first be demonstrated that there is no language deficit and that there is no disconnection between language and motor areas. A left-handed patient demonstrated bilateral agraphia and apraxia, but not aphasia, following a right parietal infarction. Preservation of the ability to type with the left hand demonstrated that the right hemisphere was not disconnected from language input. In addition, paragraphic errors while typing were shown to be secondary to left hemispatial neglect.


Evidence for a second regulatory binding site on PspF that is occupied by the C-terminal domain of PspA.
PspA is a key component of the bacterial Psp membrane-stress response system. The biochemical and functional characterization of PspA is impeded by its oligomerization and aggregation properties. It was recently possible to solve the coiled coil structure of a completely soluble PspA fragment, PspA(1-144), that associates with the σ54 enhancer binding protein PspF at its W56-loop and thereby down-regulates the Psp response. We now found that the C-terminal part of PspA, PspA(145-222), also interacts with PspF and inhibits its activity in the absence of full-length PspA. Surprisingly, PspA(145-222) effects changed completely in the presence of full-length PspA, as promoter activity was triggered instead of being inhibited under this condition. PspA(145-222) thus interfered with the inhibitory effect of full-length PspA on PspF, most likely by interacting with full-length PspA that remained bound to PspF. In support of this view, a comprehensive bacterial-2-hybrid screen as well as co-purification analyses indicated a self-interaction of PspA(145-222) and an interaction with full-length PspA. This is the first direct demonstration of PspA/PspA and PspA/PspF interactions in vivo that are mediated by the C-terminus of PspA. The data indicate that regulatory binding sites on PspF do not only exist for the N-terminal coiled coil domain but also for the C-terminal domain of PspA. The inhibition of PspF by PspA-(145-222) was reduced upon membrane stress, whereas the inhibition of PspF by PspA(1-144) did not respond to membrane stress. We therefore propose that the C-terminal domain of PspA is crucial for the regulation of PspF in response to Psp system stimuli.


[Compressed sensing magnetic resonance image reconstruction based on double sparse model].
The medical magnetic resonance (MR) image reconstruction is one of the key technologies in the field of magnetic resonance imaging (MRI). The compressed sensing (CS) theory indicates that the image can be reconstructed accurately from highly undersampled measurements by using the sparsity of the MR image. However, how to improve the image reconstruction quality by employing more sparse priors of the image becomes a crucial issue for MRI. In this paper, an adaptive image reconstruction model fusing the double dictionary learning is proposed by exploiting sparse priors of the MR image in the image domain and transform domain. The double sparse model which combines synthesis sparse model with sparse transform model is applied to the CS MR image reconstruction according to the complementarity of synthesis sparse and sparse transform model. Making full use of the two sparse priors of the image under the synthesis dictionary and transform dictionary learning, the proposed model is tackled in stages by the iterative alternating minimization algorithm. The solution procedure needs to utilize the synthesis and transform K-singular value decomposition (K-SVD) algorithms. Compared with the existing MRI models, the experimental results show that the proposed model can more efficiently improve the quality of the image reconstruction, and has faster convergence speed and better robustness to noise.


Pathological imaging-assisted cancer gene-environment interaction analysis.
Gene-environment (G-E) interactions have important implications for cancer outcomes and phenotypes beyond the main G and E effects. Compared to main-effect-only analysis, G-E interaction analysis more seriously suffers from a lack of information caused by higher dimensionality, weaker signals, and other factors. It is also uniquely challenged by the "main effects, interactions" variable selection hierarchy. Effort has been made to bring in additional information to assist cancer G-E interaction analysis. In this study, we take a strategy different from the existing literature and borrow information from pathological imaging data. Such data are a "byproduct" of biopsy, enjoys broad availability and low cost, and has been shown as informative for modeling prognosis and other cancer outcomes/phenotypes in recent studies. Building on penalization, we develop an assisted estimation and variable selection approach for G-E interaction analysis. The approach is intuitive, can be effectively realized, and has competitive performance in simulation. We further analyze The Cancer Genome Atlas (TCGA) data on lung adenocarcinoma (LUAD). The outcome of interest is overall survival, and for G variables, we analyze gene expressions. Assisted by pathological imaging data, our G-E interaction analysis leads to different findings with competitive prediction performance and stability.