On the purification of beta-bungarotoxin

It has recently been claimed that our beta-bungarotoxin preparation contained three contaminants, including a postsynaptic toxin. We have extended our purification procedure and found no evidence of such contaminants.     

Focus on function: single molecule RNA enzymology

The ability of RNA to catalyze chemical reactions was first demonstrated 25 years ago with the discovery that group I introns and RNase P function as RNA enzymes (ribozymes). Several additional ribozymes were subsequently identified, most notably the ribosome, followed by intense mechanistic studies. More recently, the introduction of single molecule tools has dissected the kinetic steps of several ribozymes in unprecedented detail and has revealed surprising heterogeneity not evident from ensemble approaches. Still, many fundamental questions of how RNA enzymes work at the molecular level remain unanswered. This review surveys the current status of our understanding of RNA catalysis at the single molecule level and discusses the existing challenges and opportunities in developing suitable assays.     

Incremental hospital charges associated with obesity as a secondary diagnosis in children

Objective: The objective was to evaluate the association of obesity as a comorbidity with hospital charges, by comparing charges for pediatric hospitalizations with vs. without obesity as a secondary diagnosis. Methods: Using the 2000 Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Database (KID), a nationally representative sample of pediatric hospital discharges, we identified the most common non‐pregnancy‐related principal diagnoses for children 2 to 18 years of age: asthma, pneumonia, affective disorders, and appendicitis. For each we compared mean charges and mean length of stay for hospitalizations with vs. without obesity as a secondary diagnosis, adjusting for relevant socio‐demographics and hospital type. Results: Among children's discharges in 2000, 1.1% listed obesity as a secondary diagnosis. These had a disproportionate likelihood of being older, black, Medicaid beneficiaries, and hospitalized at a general hospital. Adjusted mean hospital charges were significantly higher for discharges with obesity as a secondary diagnosis vs. those without: appendicitis ($14,134 vs. $11,049; p < 0.01), asthma ($7766 vs. $6043; p < 0.05), pneumonia ($12,228 vs. $9688; p < 0.05), and affective disorders ($8292 vs. $7769; p < 0.01). Whereas obesity as a secondary diagnosis was associated with a pattern of increased adjusted mean length of stay, only asthma and affective disorders had statistically significant differences (0.6 days) (p < 0.01). Conclusion: This national analysis suggests obesity as a secondary diagnosis is associated with significantly higher charges for the most common reasons for pediatric hospitalizations. This presents a financial imperative for further research to evaluate factors that contribute to higher inpatient charges related to obesity as a comorbidity and underscores the need for obesity prevention initiatives.     

Inhibition of ErbB-2 mitogenic and transforming activity by RALT, a mitogen-induced signal transducer which binds to the ErbB-2 kinase domain

The product of rat gene 33 was identified as an ErbB-2-interacting protein in a two-hybrid screen employing the ErbB-2 juxtamembrane and kinase domains as bait. This interaction was reproduced in vitro with a glutathione S-transferase fusion protein spanning positions 282 to 395 of the 459-residue gene 33 protein. Activation of ErbB-2 catalytic function was required for ErbB-2-gene 33 physical interaction in living cells, whereas ErbB-2 autophosphorylation was dispensable. Expression of gene 33 protein was absent in growth-arrested NIH 3T3 fibroblasts but was induced within 60 to 90 min of serum stimulation or activation of the ErbB-2 kinase and decreased sharply upon entry into S phase. New differentiation factor stimulation of mitogen-deprived mammary epithelial cells also caused accumulation of gene 33 protein, which could be found in a complex with ErbB-2. Overexpression of gene 33 protein in mouse fibroblasts inhibited (i) cell proliferation driven by ErbB-2 but not by serum, (ii) cell transformation induced by ErbB-2 but not by Ras or Src, and (iii) sustained activation of ERK 1 and 2 by ErbB-2 but not by serum. The gene 33 protein may convey inhibitory signals downstream to ErbB-2 by virtue of its association with SH3-containing proteins, including GRB-2, which was found to associate with gene 33 protein in living cells. These data indicate that the gene 33 protein is a feedback inhibitor of ErbB-2 mitogenic function and a suppressor of ErbB-2 oncogenic activity. We propose that the gene 33 protein be renamed with the acronym RALT (receptor-associated late transducer).     

Prevalence of Mental Distress and Associated Factors among Undergraduate Students of University of Gondar,Northwest Ethiopia: A Cross-Sectional Institutional Based Study

Background

Mental health problems affect society as a whole and no group is immune to mental disorders; however, students have significantly high level of mental distress than their community peers.

Objectives

The purpose of this study was to assess the prevalence and associated factors of mental distress among undergraduate students of University of Gondar, Northwest Ethiopia.

Methods

Institution based cross sectional study was conducted among 836 students from April 9–11/2014. Stratified multistage sampling technique was used to select the study participants. Data were collected using pretested and structured self-administered questionnaire. Bivariate and multivariate logistic regression model was fitted to identify factors associated with mental distress among students. An adjusted odds ratio with 95% confidence interval was computed to determine the level of significance.

Results

Prevalence of mental distress among students was found to be 40.9%. Female sex (AOR = 1.65; 95% CI 1.17–2.30), lack of interest towards their field of study (AOR = 2.28; 95% CI 1.49–3.50), not having close friends (AOR = 1.48; 95% CI 1.03–2.14), never attend religious programs (AOR = 1.58; 95% CI 1.02–2.46), conflict with friends (AOR = 1.93; 95% CI 1.41–2.65), having financial distress (AOR1.49 = 95% CI 1.05, 2.10), family history of mental illness (AOR = 2.12; 95% CI 1.31–3.45), Ever use of Khat (AOR = 1.71; 95% CI 1.12–2.59), lower grade than anticipated(AOR = 2.07; 95% CI 1.51–2.83), lack of vacation or break (AOR = 1.46; 95% CI 1.06–2.02), and low social support(AOR = 2.58; 95% CI 1.58–4.22) were significantly associated with mental distress.

Conclusion

The overall prevalence of mental distress among students was found to be high. Therefore, it is recommended that mental distress needs due attention and remedial action from policy makers, college officials, non-governmental organizations, parents, students and other concerned bodies.     

A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours

Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z¹⁺ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100–10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7–19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q₂₅ 14.4–Q₇₅ 29.0) and 3.8 μmol/L (Q₂₅ 1.5–Q₇₅ 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients.     

Maternal Obesity in Early Pregnancy and Risk of Adverse Outcomes

Objectives

To assess the role of the health consequences of maternal overweight and obesity at the start of pregnancy on gestational pathologies, delivery and newborn characteristics.

Methods

A cohort of pregnant women (n = 6.558) having delivered at the Maternal & Child University Hospital of Gran Canaria (HUMIGC) in 2008 has been studied. Outcomes were compared using multivariate analyses controlling for confounding variables.

Results

Compared to normoweight, overweight and obese women have greater risks of gestational diabetes mellitus (RR = 2.13 (95% CI: 1.52–2.98) and (RR = 2.85 (95% CI: 2.01–4.04), gestational hypertension (RR = 2.01 (95% CI: 1.27–3.19) and (RR = 4.79 (95% CI: 3.13–7.32) and preeclampsia (RR = 3.16 (95% CI: 1.12–8.91) and (RR = 8.80 (95% CI: 3.46–22.40). Obese women have also more frequently oligodramnios (RR = 2.02 (95% CI: 1.25–3.27), polyhydramnios. (RR = 1.76 (95% CI: 1.03–2.99), tearing (RR = 1.24 (95% CI: 1.05–1.46) and a lower risk of induced deliveries (RR = 0.83 (95% CI: 0.72–0.95). Both groups have more frequently caesarean section (RR = 1.36 (95% CI: 1.14–1.63) and (RR = 1.84 (95% CI: 1.53–2.22) and manual placenta extraction (RR = 1.65 (95% CI: 1.28–2.11) and (RR = 1.77 (95% CI: 1.35–2.33). Newborns from overweight and obese women have higher weight (p<0.001) and a greater risk of being macrosomic (RR = 2.00 (95% CI: 1.56–2.56) and (RR = 2.74 (95% CI: 2.12–3.54). Finally, neonates from obese mother have a higher risk of being admitted to special care units (RR = 1.34 (95% CI: 1.01–1.77). Apgar 1 min was significantly higher in newborns from normoweight mothers: 8.65 (95% CI: 8.62–8.69) than from overweight: 8.56 (95% CI: 8.50–8.61) or obese mothers: 8.48 (95% CI: 8.41–8.54).

Conclusion

Obesity and overweight status at the beginning of pregnancy increase the adverse outcomes of the pregnancy. It is important to promote the normalization of bodyweight in those women who intend to get pregnant and to provide appropriate advice to the obese women of the risks of obesity at the start of the pregnancy.     

Birth Preparedness and Complication Readiness among Pregnant Women in Duguna Fango District,Wolayta Zone,Ethiopia

Background

Birth Preparedness and Complication Readiness is a strategy to promote the timely use of skilled maternal and neonatal care, especially during childbirth, based on the theory that preparing for childbirth and being ready for complications reduces delays in obtaining this care.

Objective

This study was conducted to assess birth preparedness and complication readiness and its associated factors among pregnant woman in Duguna Fango District in Wolayta Zone, South Ethiopia.

Methods

A community based cross-sectional study was conducted in 2013, on a sample of 578 pregnant women. Data were collected using pre-tested and structured questionnaire. The collected data were analyzed by SPSS for windows version 16.0. The women were asked whether they followed the desired five steps while pregnant: identified a trained birth attendant, identified a health facility, arranged for transport, identified blood donor and saved money for emergency. Taking at least three steps was considered being well-prepared.

Results

Among 578 pregnant women only one tenth (10.7%) of pregnant women identified skilled provider. Only 103 (18.1%) arranged transportation to health facility. Two hundred forty eight (43.6%) identified health facility for delivery and/or for obstetric emergencies. more than half (54.1%) of families saved money for incurred costs of delivery and emergency if needed. only few 17(3%) identified potential blood donor in case of emergency. Two hundred sixty four (46.4%) of the respondents reported that they intended to deliver at home, and more than half (53.6) planned to deliver at health facilities. Overall less than one fifth 18.3% of pregnant women were well prepared. The adjusted multivariate model showed that significant predictors for being well-prepared were maternal availing of antenatal services (AOR = 2.95, 95% CI: 1.62–5.37), being pregnant for the first time (AOR = 3.37, 95% CI: 1.45–7.82), having knowledge of at least two danger signs during pregnancy (AOR = 2.81, 95% CI: 1.69–4.67) and history of past obstetric complication (AOR = 2.98, 95% CI: 1.35–6.58).

Conclusion

Birth preparedness practice in the study area was found to be low. Information, Education and Communication (IEC) on birth preparedness and complication readiness for young people should start early adolescence. The government officials and partners that are working in areas of maternal health should come up with strategies to improve birth preparedness at individual and community level.     

Food Insecurity,Food Based Coping Strategies and Suboptimal Dietary Practices of Adolescents in Jimma Zone Southwest Ethiopia

Despite the high prevalence of adolescent food insecurity in Ethiopia, there is no study which documented its association with suboptimal dietary practices. The objective of this study is to determine the association between adolescent food insecurity and dietary practices. We used data on 2084 adolescents in the age group of 13–17 years involved in the first round survey of the five year longitudinal family study in Southwest Ethiopia. Adolescents were selected using residence stratified random sampling methods. Food insecurity was measured using scales validated in developing countries. Dietary practices were measured using dietary diversity score, food variety score and frequency of consuming animal source food. Multivariable regression models were used to compare dietary behaviors by food security status after controlling for socio-demographic and economic covariates.Food insecure adolescents had low dietary diversity score (P<0.001), low mean food variety score (P<0.001) and low frequency of consuming animal source foods (P<0.001). After adjusting for other variables in a multivariable logistic regression model, adolescent food insecurity (P<0.001) and rural residence (P<0.001) were negatively associated with the likelihood of having a diversified diet (P<0.001) and frequency of consuming animal source foods, while a high household income tertile was positively associated. Similarly, multivariable linear regression model showed that adolescent food insecurity was negatively associated with food variety score, while residence in semi-urban areas (P<0.001), in urban areas (P<0.001) and high household income tertile (P = 0.013) were positively associated. Girls were less likely to have diversified diet (P = 0.001) compared with boys.Our findings suggest that food insecurity has negative consequence on optimal dietary intake of adolescents. Food security interventions should look into ways of targeting adolescents to mitigate these dietary consequences and provide alternative strategies to improve dietary quality of adolescents in Southwest Ethiopia.