The ischemic preconditioning effect of adenosine in patients with ischemic heart disease

<p>Abstract</p> <p>Introduction</p> <p><it>In vivo </it>and <it>in vitro </it>evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans.</p> <p>Aims</p> <p>We hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV) systolic function.</p> <p>Materials and methods</p> <p>We studied nine severely symptomatic male patients with severe coronary artery disease. Myocardial ischemia was induced by exercise on two separate occasions and quantified by Tissue Doppler Echocardiography. Prior to the exercise test, intravenous low-dose adenosine or placebo was infused over ten minutes according to a randomized, double blind, cross-over protocol. The LV walls were defined as ischemic if a reduction, no increment, or an increment of < 15% in peak systolic velocity (PSV) was observed during maximal exercise compared to the baseline values observed prior to placebo-infusion. Otherwise, the LV walls were defined as non-ischemic.</p> <p>Results</p> <p>PSV increased from baseline to maximal exercise in non-ischemic walls both during placebo (<it>P </it>= 0.0001) and low-dose adenosine infusion (<it>P </it>= 0.0009). However, in the ischemic walls, PSV increased only during low-dose adenosine infusion <it>(P </it>= 0.001), while no changes in PSV occurred during placebo infusion (<it>P </it>= NS).</p> <p>Conclusion</p> <p>Low-dose adenosine infusion reduced the ischemic burden and improved LV regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming that adenosine is a potential preconditioning agent in humans.</p

Surveillance of HIV and syphilis infections among antenatal clinic attendees in Tanzania-2003/2004

BACKGROUND: This paper presents the prevalence of human immunodeficiency virus (HIV) and syphilis infections among women attending antenatal clinics (ANC) in Tanzania obtained during the 2003/2004 ANC surveillance. METHODS: Ten geographical regions; six of them were involved in a previous survey, while the remaining four were freshly selected on the basis of having the largest population among the remaining 20 regions. For each region, six ANC were selected, two from each of three strata (urban, peri-urban and rural). Three of the sites did not participate, resulting into 57 surveyed clinics. 17,813 women who were attending the chosen clinics for the first time for any pregnancy between October 2003 and January 2004. Patient particulars were obtained by interview and blood specimens were drawn for HIV and syphilis testing. HIV testing was done anonymously and the results were unlinked. RESULTS: Of the 17,813 women screened for HIV, 1,545 (8.7% (95% CI = 8.3–9.1)) tested positive with the highest prevalence in women aged 25–34 years (11%), being higher among single women (9.7%) than married women (8.6%) (p < 0.07), and increased with level of education from 5.2% among women with no education to 9.3% among those at least primary education (p < 0.001). Prevalence ranged from 4.8% (95% CI = 3.8% – 9.8%) in Kagera to 15.3% (95% CI = 13.9% – 16.8%) in Mbeya and was; 3.7%, 4.7%, 9.1%, 11.2% and 15.3% for rural, semi-urban, road side, urban and 15.3% border clinics, respectively (p < 0.001). Of the 17,323 women screened for syphilis, 1265 (7.3% (95%CI = 6.9–7.7)) were positive, with highest prevalence in the age group 35–49 yrs (10.4%) (p < 0.001), and being higher among women with no education than those with some education (9.8% versus 6.8%) (p < 0.0001), but marital status had no influence. Prevalence ranged from 2.1% (95% CI = 1.4% – 3.0%) in Kigoma to 14.9% (95% CI = 13.3%-16.6%) in Kagera and was 16.0% (95% CI = 13.3–18.9), 10.5% (95% CI = 9.5–11.5) and 5.8% (95% CI = 5.4–6.3) for roadside, rural and urban clinics, respectively. Syphilis and HIV co-infection was seen in 130/17813 (0.7%). CONCLUSION: The high HIV prevalence observed among the ANC clinic attendees in Tanzania call for expansion of current voluntary counselling and testing (VCT) services and access to antiretroviral drugs (ARV) in the clinics. There is also a need for modification of obstetric practices and infant feeding options in HIV infection in order to prevent mother to child transmission of HIV. To increase uptake to HIV testing the opt-out strategy in which all clients are offered HIV testing is recommended in order to meet the needs of as many pregnant women as possible

Hair Cell Bundles: Flexoelectric Motors of the Inner Ear

Microvilli (stereocilia) projecting from the apex of hair cells in the inner ear are actively motile structures that feed energy into the vibration of the inner ear and enhance sensitivity to sound. The biophysical mechanism underlying the hair bundle motor is unknown. In this study, we examined a membrane flexoelectric origin for active movements in stereocilia and conclude that it is likely to be an important contributor to mechanical power output by hair bundles. We formulated a realistic biophysical model of stereocilia incorporating stereocilia dimensions, the known flexoelectric coefficient of lipid membranes, mechanical compliance, and fluid drag. Electrical power enters the stereocilia through displacement sensitive ion channels and, due to the small diameter of stereocilia, is converted to useful mechanical power output by flexoelectricity. This motor augments molecular motors associated with the mechanosensitive apparatus itself that have been described previously. The model reveals stereocilia to be highly efficient and fast flexoelectric motors that capture the energy in the extracellular electro-chemical potential of the inner ear to generate mechanical power output. The power analysis provides an explanation for the correlation between stereocilia height and the tonotopic organization of hearing organs. Further, results suggest that flexoelectricity may be essential to the exquisite sensitivity and frequency selectivity of non-mammalian hearing organs at high auditory frequencies, and may contribute to the “cochlear amplifier” in mammals

Probabilistic Inference for Nucleosome Positioning with MNase-Based or Sonicated Short-Read Data

We describe a model-based method, PING, for predicting nucleosome positions in MNase-Seq and MNase- or sonicated-ChIP-Seq data. PING compares favorably to NPS and TemplateFilter in scalability, accuracy and robustness to low read density. To demonstrate that PING predictions from widely available sonicated data can have sufficient spatial resolution to be to be useful for biological inference, we use Illumina H3K4me1 ChIP-seq data to detect changes in nucleosome positioning around transcription factor binding sites due to tamoxifen stimulation, to discriminate functional and non-functional transcription factor binding sites more effectively than with enrichment profiles, and to confirm that the pioneer transcription factor Foxa2 associates with the accessible major groove of nucleosomal DNA

Patient attributes warranting consideration in clinical practice guidelines, health workforce planning and policy

<p>Abstract</p> <p>Background</p> <p>In order for clinical practice guidelines (CPGs) to meet their broad objective of enhancing the quality of care and supporting improved patient outcomes, they must address the needs of diverse patient populations. We set out to explore the patient attributes that are likely to demand a unique approach to the management of chronic disease, and which are crucial if evidence or services planning is to reflect clinic populations. These were incorporated into a new conceptual framework; using diabetes mellitus as an exemplar.</p> <p>Methods</p> <p>The patient attributes that informed the framework were identified from CPGs, the diabetes literature, an expert academic panel, and two cross-disciplinary panels; and agreed upon using a modified nominal group technique.</p> <p>Results</p> <p>Full consensus was reached on twenty-four attributes. These factors fell into one of three themes: (1) type/stage of disease, (2) morbid events, and (3) factors impacting on capacity to self-care. These three themes were incorporated in a convenient way in the workforce evidence-based (WEB) model.</p> <p>Conclusions</p> <p>While biomedical factors are frequently recognised in published clinical practice guidelines, little attention is given to attributes influencing a person's capacity to self-care. Paying explicit attention to predictable threats to effective self-care in clinical practice guidelines, by drawing on the WEB model, may assist in refinements that would address observed disparities in health outcomes across socio-economic groups. The WEB model also provides a framework to inform clinical training, and health services and workforce planning and research; including the assessment of healthcare needs, and the allocation of healthcare resources.</p

The Crystal Structure of the Escherichia coli Autoinducer-2 Processing Protein LsrF

Many bacteria produce and respond to the quorum sensing signal autoinducer-2 (AI-2). Escherichia coli and Salmonella typhimurium are among the species with the lsr operon, an operon containing AI-2 transport and processing genes that are up regulated in response to AI-2. One of the Lsr proteins, LsrF, has been implicated in processing the phosphorylated form of AI-2. Here, we present the structure of LsrF, unliganded and in complex with two phospho-AI-2 analogues, ribose-5-phosphate and ribulose-5-phosphate. The crystal structure shows that LsrF is a decamer of (αβ)8-barrels that exhibit a previously unseen N-terminal domain swap and have high structural homology with aldolases that process phosphorylated sugars. Ligand binding sites and key catalytic residues are structurally conserved, strongly implicating LsrF as a class I aldolase

Dynamics of the Leaf-Litter Arthropod Fauna Following Fire in a Neotropical Woodland Savanna

Fire is an important agent of disturbance in tropical savannas, but relatively few studies have analyzed how soil-and-litter dwelling arthropods respond to fire disturbance despite the critical role these organisms play in nutrient cycling and other biogeochemical processes. Following the incursion of a fire into a woodland savanna ecological reserve in Central Brazil, we monitored the dynamics of litter-arthropod populations for nearly two years in one burned and one unburned area of the reserve. We also performed a reciprocal transplant experiment to determine the effects of fire and litter type on the dynamics of litter colonization by arthropods. Overall arthropod abundance, the abundance of individual taxa, the richness of taxonomic groups, and the species richness of individual taxa (Formiciade) were lower in the burned site. However, both the ordinal-level composition of the litter arthropod fauna and the species-level composition of the litter ant fauna were not dramatically different in the burned and unburned sites. There is evidence that seasonality of rainfall interacts with fire, as differences in arthropod abundance and diversity were more pronounced in the dry than in the wet season. For many taxa the differences in abundance between burned and unburned sites were maintained even when controlling for litter availability and quality. In contrast, differences in abundance for Collembola, Formicidae, and Thysanoptera were only detected in the unmanipulated samples, which had a lower amount of litter in the burned than in the unburned site throughout most of our study period. Together these results suggest that arthropod density declines in fire-disturbed areas as a result of direct mortality, diminished resources (i.e., reduced litter cover) and less favorable microclimate (i.e., increased litter desiccation due to reduction in tree cover). Although these effects were transitory, there is evidence that the increasingly prevalent fire return interval of only 1–2 years may jeopardize the long-term conservation of litter arthropod communities