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 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

Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay.

Analysis of cell-free DNA using next-generation sequencing (NGS) is a powerful tool for the detection/monitoring of alterations present in circulating tumor DNA (ctDNA). Plasma extracted from 171 patients with a variety of cancers was analyzed for ctDNA (54 genes and copy number variants (CNVs) in three genes (EGFR, ERBB2 and MET)). The most represented cancers were lung (23%), breast (23%), and glioblastoma (19%). Ninety-nine patients (58%) had at least one detectable alteration. The most frequent alterations were TP53 (29.8%), followed by EGFR (17.5%), MET (10.5%), PIK3CA (7%), and NOTCH1 (5.8%). In contrast, of 222 healthy volunteers, only one had an aberration (TP53). Ninety patients with non-brain tumors had a discernible aberration (65% of 138 patients; in 70% of non-brain tumor patients with an alteration, the anomaly was potentially actionable). Interestingly, nine of 33 patients (27%) with glioblastoma had an alteration (6/33 (18%) potentially actionable). Overall, sixty-nine patients had potentially actionable alterations (40% of total; 69.7% of patients (69/99) with alterations); 68 patients (40% of total; 69% of patients with alterations), by a Food and Drug Administration (FDA) approved drug. In summary, 65% of diverse cancers (as well as 27% of glioblastomas) had detectable ctDNA aberration(s), with the majority theoretically actionable by an approved agent

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

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

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 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

A mitochondria-targeted mass spectrometry probe to detect glyoxals: implications for diabetes

The glycation of protein and nucleic acids that occurs as a consequence of hyperglycaemia disrupts cell function and contributes to many pathologies, including those associated with diabetes and aging. Intracellular glycation occurs following the generation of the reactive 1,2-dicarbonyls methylglyoxal and glyoxal and disruption to mitochondrial function is associated with hyperglycemia. However, the contribution of these reactive dicarbonyls to mitochondrial damage in pathology is unclear due to uncertainties about their levels within mitochondria in cells and in vivo. To address this we have developed a mitochondria-targeted reagent (MitoG) designed to assess the levels of mitochondrial dicarbonyls within cells. MitoG comprises a lipophilic triphenylphosphonium cationic function, which directs the molecules to mitochondria within cells and an o-phenylenediamine moiety that reacts with dicarbonyls to give distinctive and stable products. The extent of accumulation of these diagnostic heterocyclic products can be readily and sensitively quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), enabling changes to be determined. Using the MitoG-based analysis we assessed the formation of methylglyoxal and glyoxal in response to hyperglycaemia in cells in culture and in the Akita mouse model of diabetes in vivo. These findings indicated that the levels of methylglyoxal and glyoxal within mitochondria increase during hyperglycaemia in both cells and in vivo, suggesting that they can contribute to the pathological mitochondrial dysfunction that occurs in diabetes and aging