Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Background Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. Methods We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution. Results Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms). Conclusion Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve

Social disorganization and history of child sexual abuse against girls in sub-Saharan Africa : a multilevel analysis

Background: Child sexual abuse (CSA) is a considerable public health problem. Less focus has been paid to the role of community level factors associated with CSA. The aim of this study was to examine the association between neighbourhood-level measures of social disorganization and CSA. Methods: We applied multiple multilevel logistic regression analysis on Demographic and Health Survey data for 6,351 adolescents from six countries in sub-Saharan Africa between 2006 and 2008. Results: The percentage of adolescents that had experienced CSA ranged from 1.04% to 5.84%. There was a significant variation in the odds of reporting CSA across the communities, suggesting 18% of the variation in CSA could be attributed to community level factors. Respondents currently employed were more likely to have reported CSA than those who were unemployed (odds ratio [OR] = 2.05, 95% confidence interval [CI] 1.48 to 2.83). Respondents from communities with a high family disruption rate were 57% more likely to have reported CSA (OR=1.57, 95% CI 1.14 to 2.16). Conclusion: We found that exposure to CSA was associated with high community level of family disruption, thus suggesting that neighbourhoods may indeed have significant important effects on exposure to CSA. Further studies are needed to explore pathways that connect the individual and neighbourhood levels, that is, means through which deleterious neighbourhood effects are transmitted to individuals

Author Self-Citation in the General Medicine Literature

Background: Author self-citation contributes to the overall citation count of an article and the impact factor of the journal in which it appears. Little is known, however, about the extent of self-citation in the general clinical medicine literature. The objective of this study was to determine the extent and temporal pattern of author self-citation and the article characteristics associated with author self-citation. Methodology/Principal Findings: We performed a retrospective cohort study of articles published in three high impact general medical journals (JAMA, Lancet, and New England Journal of Medicine) between October 1, 1999 and March 31, 2000. We retrieved the number and percentage of author self-citations received by the article since publication, as of June 2008, from the Scopus citation database. Several article characteristics were extracted by two blinded, independent reviewers for each article in the cohort and analyzed in multivariable linear regression analyses. Since publication, author self-citations accounted for 6.5 % (95 % confidence interval 6.3–6.7%) of all citations received by the 328 articles in our sample. Selfcitation peaked in 2002, declining annually thereafter. Studies with more authors, in cardiovascular medicine or infectious disease, and with smaller sample size were associated with more author self-citations and higher percentage of author selfcitation (all p#0.01). Conclusions/Significance: Approximately 1 in 15 citations of articles in high-profile general medicine journals are autho

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

Quantification of atopy, lung function and airway hypersensitivity in adults

<p>Abstract</p> <p>Background</p> <p>Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR).</p> <p>Objective</p> <p>To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK.</p> <p>Methods</p> <p>FEV₁ and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes.</p> <p>Results</p> <p>Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV₁ (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10^-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10^-8, cat p = 3.93 × 10^-10, dog p = 3.03 × 10^-15, grass p = 2.95 × 10^-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control).</p> <p>Conclusions</p> <p>In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR.</p

Diagnosis and neurosurgical treatment of glossopharyngeal neuralgia: clinical findings and 3-D visualization of neurovascular compression in 19 consecutive patients

Glossopharyngeal neuralgia is a rare condition with neuralgic sharp pain in the pharyngeal and auricular region. Classical glossopharyngeal neuralgia is caused by neurovascular compression at the root entry zone of the nerve. Regarding the rare occurrence of glossopharyngeal neuralgia, we report clinical data and magnetic resonance imaging (MRI) findings in a case series of 19 patients, of whom 18 underwent surgery. Two patients additionally suffered from trigeminal neuralgia and three from additional symptomatic vagal nerve compression. In all patients, ipsilateral neurovascular compression syndrome of the IX cranial nerve could be shown by high-resolution MRI and image processing, which was confirmed intraoperatively. Additional neurovascular compression of the V cranial nerve was shown in patients suffering from trigeminal neuralgia. Vagal nerve neurovascular compression could be seen in all patients during surgery. Sixteen patients were completely pain free after surgery without need of anticonvulsant treatment. As a consequence of the operation, two patients suffered from transient cerebrospinal fluid hypersecretion as a reaction to Teflon implants. One patient suffered postoperatively from deep vein thrombosis and pulmonary embolism. Six patients showed transient cranial nerve dysfunctions (difficulties in swallowing, vocal cord paresis), but all recovered within 1 week. One patient complained of a gnawing and burning pain in the cervical area. Microvascular decompression is a second-line treatment after failure of standard medical treatment with high success in glossopharyngeal neuralgia. High-resolution MRI and 3D visualization of the brainstem and accompanying vessels as well as the cranial nerves is helpful in identifying neurovascular compression before microvascular decompression procedure

Guidelines for the labelling of leucocytes with 99mTc-HMPAO

We describe here a protocol for labelling autologous white blood cells with 99mTc-HMPAO based on previously published consensus papers and guidelines. This protocol includes quality control and safety procedures and is in accordance with current European Union regulations and International Atomic Energy Agency recommendations

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

Effect of bio-engineering on size, shape, composition and rigidity of bacterial microcompartments

Bacterial microcompartments (BMCs) are proteinaceous organelles that are found in a broad range of bacteria and are composed of an outer shell that encases an enzyme cargo representing a specific metabolic process. The outer shell is made from a number of different proteins that form hexameric and pentameric tiles, which interact to allow the formation of a polyhedral edifice. We have previously shown that the Citrobacter freundii BMC associated with 1,2-propanediol utilization can be transferred into Escherichia coli to generate a recombinant BMC and that empty BMCs can be formed from just the shell proteins alone. Herein, a detailed structural and proteomic characterization of the wild type BMC is compared to the recombinant BMC and a number of empty BMC variants by 2D-gel electrophoresis, mass spectrometry, transmission electron microscopy (TEM) and atomic force microscopy (AFM). Specifically, it is shown that the wild type BMC and the recombinant BMC are similar in terms of composition, size, shape and mechanical properties, whereas the empty BMC variants are shown to be smaller, hollow and less malleable

Avoiding Treatment Interruptions: What Role Do Australian Community Pharmacists Play?

OBJECTIVE: To explore the reported practice of Australian community pharmacists when dealing with medication supply requests in absence of a valid prescription. METHODS: Self-administered questionnaire was posted to 1490 randomly selected community pharmacies across all Australian states and territories. This sample was estimated to be a 20% of all Australian community pharmacies. RESULTS: Three hundred eighty five pharmacists participated in the study (response rate achieved was 27.9% (there were 111 undelivered questionnaires). Respondents indicated that they were more likely to provide medications to regular customers without a valid prescription compared to non-regular customers (p&lt;0.0001). However, supply was also influenced by the type of prescription and the medication requested. In the case of type of prescription (Standard, Authority or Private) this relates to the complexity/probability of obtaining a valid prescription from the prescriber at a later date (i.e. supply with an anticipated prescription). Decisions to supply and/or not supply related to medication type were more complex. For some cases, including medication with potential for abuse, the practice and/or the method of supply varied significantly according to age and gender of the pharmacist, and pharmacy location (p&lt;0.05). CONCLUSIONS: Although being a regular customer does not guarantee a supply, results of this study reinforce the importance for patients having a regular pharmacy, where pharmacists were more likely to continue medication supply in cases of patients presenting without a valid prescription. We would suggest, more flexible legislation should be implemented to allow pharmacists to continue supplying of medication when obtaining a prescription is not practical