Pharmacological inhibition of c-Abl compromises genetic stability and DNA repair in Bcr-Abl-negative cells

Imatinib inhibits the kinase activity of Bcr-Abl and is currently the most effective drug for treatment of chronic myeloid leukemia (CML). Imatinib also blocks c-Abl, a physiological tyrosine kinase activated by a variety of stress signals including damaged DNA. We investigated the effect of pharmacological inhibition of c-Abl on the processing of irradiation-induced DNA damage in Bcr-Abl-negative cells. Cell lines and peripheral blood mononuclear cells (PBMCs) from healthy volunteers were treated with imatinib or dasatinib before gamma-irradiation. Inhibition of c-Abl caused an enhanced irradiation-induced mutation frequency and slowdown of DNA repair, whereas imatinib was ineffective in cells expressing a T315I variant of c-Abl. Mutation frequency and repair kinetics were also studied in c-Abl-/- murine embryonic fibroblasts (MEFs) retransfected with wild-type c-Abl (wt-Abl) or a kinase-defect variant of Abl (KD-Abl). Enhanced mutation frequency as well as delayed DNA repair was observed in cells expressing KD-Abl. These data indicate that pharmacological inhibition of c-Abl compromises DNA-damage response

Pseudo-methemoglobinemia Induced by Phenazopyridine, A Diagnostic Challenge

A 58 y/o female presented to her clinician with perioral and nailbed cyanosis. She denied any cardiopulmonary symptoms. She had been taking phenazopyridine daily for dysuria over the past two weeks. Pulse oximetry showed a saturation of 84% on room air. Basic laboratory analysis was unrevealing, and blood gas was normal, but methemoglobin (MetHb) levels were markedly elevated on CO-oximetry. Phenazopyridine was stopped, methylene blue therapy was initiated, and the patient was admitted for observation. Despite this intervention her reported levels of MetHb remained high. The patient remained asymptomatic and a blood specimen sent to a larger healthcare system showed MetHb within normal limits. It was at this time the suspicion of sulfhemoglobinemia, a rare and typically asymptomatic condition, was considered and the patient was discharged and scheduled for follow-up. Sulfhemoglobinemia was confirmed at a separate reference laboratory. Her blue discoloration slowly resolved over the following weeks. Not all CO-oximeters are able to distinguish MetHb from SulfHb and some will report back SulfHb as false-positive MetHb. It is important to distinguish these hemoglobin variants because prognosis and treatment are vastly different. This case emphasizes that one needs to consider sulfhemoglobinemia in a cyanotic, asymptomatic patient that is unresponsive to methylene blue treatment even in the face of elevated methemoglobin levels on CO-oximetry

The Performance of a Rapid Diagnostic Test in Detecting Malaria Infection in Pregnant Women and the Impact of Missed Infections.

BACKGROUND: Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern. METHODS: Primigravidae and secundigravidae who participated in the ISTp arm of a noninferiority trial in 4 West African countries were screened with an HRP2/pLDH RDT on enrollment and, in Ghana, at subsequent antenatal clinic (ANC) visits. Blood samples were examined subsequently by microscopy and by a polymerase chain reaction (PCR) assay. RESULTS: The sensitivity of the RDT to detect peripheral blood infections confirmed by microscopy and/or PCR at enrollment ranged from 91% (95% confidence interval [CI], 88%, 94%) in Burkina Faso to 59% (95% CI, 48%, 70% in The Gambia. In Ghana, RDT sensitivity was 89% (95% CI, 85%, 92%), 83% (95% CI, 76%, 90%) and 77% (95% CI, 67%, 86%) at enrollment, second and third ANC visits respectively but only 49% (95% CI, 31%, 66%) at delivery. Screening at enrollment detected 56% of all infections detected throughout pregnancy. Seventy-five RDT negative PCR or microscopy positive infections were detected in 540 women; these were not associated with maternal anemia, placental malaria, or low birth weight. CONCLUSIONS: The sensitivity of an RDT to detect malaria in primigravidae and secundigravidae was high at enrollment in 3 of 4 countries and, in Ghana, at subsequent ANC visits. In Ghana, RDT negative malaria infections were not associated with adverse birth outcomes but missed infections were uncommon

Mineral magnetism of dusty olivine:A credible recorder of pre-accretionary remanence

The magnetic properties of olivine-hosted Fe-Ni particles have been studied to assess the potential of “dusty olivine” to retain a pre-accretionary remanence in chondritic meteorites. Both body-centered (bcc) and face-centered cubic (fcc) Fe-Ni phases were formed by reduction of a terrestrial olivine precursor. The presence of Ni complicates the magnetic properties during heating and cooling due to the fcc-bcc martensitic transition. First-order reversal curve (FORC) diagrams contain a central ridge with a broad coercivity distribution extending to 600 mT, attributed to non-interacting single-domain (SD) particles, and a “butterfly” structure extending to 250 mT, attributed to single-vortex (SV) states. SD and SV states were imaged directly using electron holography. The location of the SD/SV boundary is broadly consistent with theoretical predictions. A method to measure the volume of individual SD particles using electron holography is presented. Combining the volume information with constraints on coercivity, we calculate the thermal relaxation characteristics of the particles and demonstrate that the high-coercivity component of remanance would remain stable for 4.6 Ga, even at temperatures approaching the Curie temperature of pure Fe. The high coercivity of the particles, together with the chemical protection offered by the surrounding olivine, is likely to make them resistant to shock remagnetization, isothermal remagnetization and terrestrial weathering, making dusty olivine a credible recorder of pre-accretionary magnetic fields

The Impact of Extended Family Ties on the Academic Performance of Students in Segbewema Town

The study was carried out in Segbewema Njaluahun Chiefdom of the Kailahun District in the Eastern Region of Sierra Leone Segbewema is the Administrative Center of the Njaluahun Chiefdom where vegetable gardening is done on an appreciable scale especially by women both in the dry and the rainy seasons The study adopted a case study to explore the impact of extended family ties on the academic performance of children in Segbewema The study sample comprised of 60 respondents made up of 30 teachers 5 traders 5 commercial motor bike riders 5 NGO workers and 15 pupils The major instruments used to collect data for this study were questionnaire interview and personal observation Questionnaires were divided into six sections to reflect each objective The questions were pretested to ascertain the uniformity of items The data collected from the questionnaires interviews and observation were analyzed both quantitatively and qualitatively The quantitative data was analyzed in tables and percentages and qualitative data was analyzed in narrative form Sierra Leone has a projected population of about 7 100 000 by the provisional result of the 2015 National population and Housing Census and with a predominately extended family structure that has the likelihood to be impacted with disadvantages associated with the family tie syste

The scope of science for the International Polar Year, 2007-2008

The International Polar Year 2007““2008 will be the largest internationally coordinated research programme in 50 years. It will be an intensive period of interdisciplinary science focused on the Arctic and the Antarctic. IPY 2007““2008 research activities were assembled from the ideas of researchers in more than 60 countries. A total of 228 projects have been endorsed by the ICSU/WMO Joint Committee for IPY 2007““2008. These projects have a strong interdisciplinary emphasis and address the six themes as well as education and outreach objectives. IPY projects will exploit new technological and logistical capabilities and strengthen international coordination of research. They aim to attract, engage and develop a new generation of researchers and raise the awareness, interest and understanding of polar residents, educators, students, the general public and decision makers worldwide. IPY projects will collect a broad-ranging set of samples, data and information which will be made available to an unprecedented degree. IPY 2007““2008 aims to leave a legacy of enhanced observational systems, facilities and infrastructure. The observational networks to be established during IPY include integrated ocean observing systems in both the Arctic and Southern Oceans, coordinated acquisition of satellite data products from multiple space agencies and observational systems for astronomy, sun““earth physics, atmospheric chemistry, meteorology, ecosystems, permafrost, glaciers and geophysics. Many observing systems within IPY will be developed within the framework of existing international global observing systems

Methods of nutrition surveillance in low-income countries

Background In 1974 a joint FAO/UNICEF/WHO Expert Committee met to develop methods for nutrition surveillance. There has been much interest and activity in this topic since then, however there is a lack of guidance for practitioners and confusion exists around the terminology of nutrition surveillance. In this paper we propose a classification of data collection activities, consider the technical issues for each category, and examine the potential applications and challenges related to information and communication technology. Analysis There are three major approaches used to collect primary data for nutrition surveillance: repeated cross-sectional surveys; community-based sentinel monitoring; and the collection of data in schools. There are three major sources of secondary data for surveillance: from feeding centres, health facilities, and community-based data collection, including mass screening for malnutrition in children. Surveillance systems involving repeated surveys are suitable for monitoring and comparing national trends and for planning and policy development. To plan at a local level, surveys at district level or in programme implementation areas are ideal, but given the usually high cost of primary data collection, data obtained from health systems are more appropriate provided they are interpreted with caution and with contextual information. For early warning, data from health systems and sentinel site assessments may be valuable, if consistent in their methods of collection and any systematic bias is deemed to be steady. For evaluation purposes, surveillance systems can only give plausible evidence of whether a programme is effective. However the implementation of programmes can be monitored as long as data are collected on process indicators such as access to, and use of, services. Surveillance systems also have an important role to provide information that can be used for advocacy and for promoting accountability for actions or lack of actions, including service delivery. Conclusion This paper identifies issues that affect the collection of nutrition surveillance data, and proposes definitions of terms to differentiate between diverse sources of data of variable accuracy and validity. Increased interest in nutrition globally has resulted in high level commitments to reduce and prevent undernutrition. This review helps to address the need for accurate and regular data to convert these commitments into practice

Assessment of hygienic practices in beef cattle slaughterhouses and retail shops in Bishoftu, Ethiopia : implications for public health

Understanding the potential drivers of microbial meat contamination along the entire meat supply chain is needed to identify targets for interventions to reduce the number of meatborne bacterial outbreaks. We assessed the hygienic practices in cattle slaughterhouses (28 employees) and retail shops (127 employees) through face-to-face interviews and direct personal observations. At the slaughterhouses, stunning, de-hiding and evisceration in vertical position, carcass washing and separate storage of offal were the identified good practices. Lack of hot water baths, absence of a chilling room, infrequent hand washing, insufficiently trained staff and irregular medical check-up were practices that lead to unhygienic handling of carcasses. At the retail shops, cleaning equipment using soap and hot water (81%), storing unsold meat in refrigerators (92%), concrete floors and white painted walls and ceilings were good practices. Adjacently displaying offal and meat (39%), lack of a cold chain, wrapping meat with plastic bags and newspapers, using a plastic or wooden cutting board (57%), infrequent washing of equipment and floors, and inadequately trained employees were practices that could result in unhygienic handling of beef. Our study identified unhygienic practices both at the slaughterhouses and retail shops that can predispose the public to meatborne infections, which could be improved through training and implementation of quality control systems

Prevalence and Serotype Diversity of Salmonella in Apparently Healthy Cattle: Systematic Review and Meta-Analysis of Published Studies, 2000–2017

Salmonellosis is a leading cause of foodborne illnesses in humans with cattle being one of the reservoirs for Salmonella. We estimated a pooled prevalence of Salmonella in apparently healthy cattle and examined serotype diversity through systematic review and meta-analysis of studies published between 2000 and 2017. Peer reviewed publications reporting the prevalence of Salmonella in cattle were searched through five electronic databases (PubMed, Google scholar, Agricola, Scopus, CAB direct) and through manual search. We obtained 71 publications with 75 datasets consisting a total of 52,766 animals examined and 5,010 Salmonella positive cattle from 29 countries in six continents (except from Antarctica). Pooled prevalence of Salmonella in cattle was 9% (95% confidence interval: 7–11%). Significantly high heterogeneity (I2 = 98.7%, P < 0.01) was observed among all studies as well as within continents. Prevalence varied from 2% (Europe) to 16% (North America). Overall, 143 different serotypes were reported with the most diverse serotypes being reported from Africa (76 different serotypes) followed by North America (49 serotypes). The 10 most frequently reported serotypes (Montevideo, Typhimurium, Kentucky, Meleagridis, Anatum, Cerro, Mbandaka, Muenster, Newport, and Senftenberg) accounted for 65% of the isolates for which specific serotype information was reported. Salmonella Montevideo and S. Dublin are the most frequently reported serotypes in North America and Europe, respectively, while S. Typhimurium was the most frequent in Africa, Asia and Australasia. Our results indicated variability both in the prevalence and serotype diversity of Salmonella in cattle across continents. Although all Salmonella serotypes are potentially pathogenic to humans, five (Montevideo, Typhimurium, Anatum, Mbandaka, and Newport) of the top 10 serotypes identified in this study are among the serotypes most commonly associated with clinical illnesses in humans