Educational outcomes of Helping Babies Breathe training at a community hospital in Honduras

Objectives: Helping Babies Breathe is an evidence-based curriculum designed to teach basic neonatal resuscitation in low-resource countries. The purpose of this study was to evaluate the acquisition of knowledge and skills following this training and correlation of learner characteristics to performance in a Spanish-speaking setting. Methods: Thirty-one physicians and 39 nurses completed Helping Babies Breathe training at a Honduran community hospital. Trainee knowledge and skills were evaluated before and after the training using a multiple-choice questionnaire, bag-mask ventilation skills test, and two objective structured clinical exams (OSCEs). Linear mixed-effects models were used to analyze assessment scores pre- and post-training by profession (physician or nurse) while controlling for covariates. Results: Helping Babies Breathe training resulted in significant increases in mean scores for the multiple-choice question test, bag-mask ventilation skills test, and OSCE B. Time to initiation of effective bag-mask ventilation decreased from a mean of 74.8 to 68.4 s. Despite this improvement in bag-mask ventilation, only 42 % of participants were able to initiate effective bag-mask ventilation within the Golden Minute. Although physicians scored higher on the pre-test multiple-choice questions and bag-mask ventilation, nurses demonstrated a greater mean difference in scores after training. OSCE B scores pre- and post-training increased similarly between professions. Nurses’ and physicians’ performance in simulation was not significantly different after the training. Assessment scores and course feedback indicated a need for more skills practice, particularly with bag-mask ventilation. Conclusions: When evaluated immediately after an initial workshop, Helping Babies Breathe training resulted in significant gains in neonatal resuscitation knowledge and skills. Following training, nurses, who commonly do not perform these skills in real-life situations, were able to perform at a similar level to physicians. Further studies are necessary to determine how to sustain this knowledge and skills over time, tailor the course to learner characteristics, and whether this training translates into improvements in clinical practice

High Glucose-Mediated STAT3 Activation in Endometrial Cancer Is Inhibited by Metformin: Therapeutic Implications for Endometrial Cancer

<div><p>Objectives</p><p>STAT3 is over-expressed in endometrial cancer, and diabetes is a risk factor for the development of type 1 endometrial cancer. We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin.</p><p>Methods</p><p>In Ishikawa (grade 1) endometrial cancer cells subjected to media with low, normal, or high concentrations of glucose, expression of STAT3 and its target proteins was evaluated by real-time quantitative PCR (qPCR). Ishikawa cells were treated with metformin and assessed with cell proliferation, survival, migration, and ubiquitin assays, as well as Western blot and qPCR. Expression of apoptosis proteins was evaluated with Western blot in Ishikawa cells transfected with a STAT3 overexpression plasmid and treated with metformin. A xenograft tumor model was used for studying the <i>in vivo</i> efficacy of metformin.</p><p>Results</p><p>Expression of STAT3 and its target proteins was increased in Ishikawa cells cultured in high glucose media. <i>In vitro</i>, metformin inhibited cell proliferation, survival and migration but induced apoptosis. Metformin reduced expression levels of pSTAT3 ser727, total STAT3, and its associated cell survival and anti-apoptotic proteins. Additionally, metformin treatment was associated with increased degradation of pSTAT3 ser727. No change in apoptotic protein expression was noticed with STAT3 overexpression in Ishikawa cells. <i>In vivo</i>, metformin treatment led to a decrease in tumor weight as well as reductions of STAT3, pSTAT3 ser727, its target proteins.</p><p>Conclusions</p><p>These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin.</p></div

Expression of apoptosis and cell proliferation-related proteins in metformin-treated grade 1 endometrial cancer cells overexpressing STAT3.

<p>Ishikawa endometrial cancer cells were transfected with a STAT3-overexpressing plasmid. <b>A</b>. Western blot confirming overexpression of pSTAT3 ser727 and total STAT3. <b>B</b>. Western blot of proteins involved in apoptosis or cell proliferation in control or STAT3-overexpressing Ishikawa cells treated with control or 20 mM metformin in high-glucose medium for 48h. (C: control, TR: transfection reagent only, OE: transfected with STAT3-overexpressing plasmid, Ctrl: control, Met: metformin).</p

Relative expression of STAT3 in grade 1 endometrial cancer cells with respect to glucose concentration.

<p><b>A & B</b>. Ishikawa cells were cultured in low, normal, or high glucose media for 24 hours. Relative expression of STAT3 and its regulatory genes were calculated by normalizing the values of normal glucose to 1. <b>C</b>. STAT3-associated microRNA was then evaluated with qPCR. Groups significantly different than control (p<0.05) are indicated with an asterisk (*).</p

Degradation of pSTAT3 ser727 in grade 1 endometrial cancer cells treated with meformin.

<p>After Ishikawa cells were treated with control, 10 mM, or 20 mM metformin in high glucose media for 48h, samples were subjected to ubiquitin assay. The ubiquitinated proteins were subjected to immunoblot for pSTAT3 Ser727 and blotted with ubiquitin antibody. A ubiquitination smear of pSTAT3 Ser727 is seen in the metformin treated ishikawa cells under proteasomal inhibition using MG-132.</p

Xenograft endometrial tumor weight and expression of STAT3 in mice treated with metformin.

<p>A xenograft study was done in which nude mice were injected with 1 x 10⁶ Ishikawa endometrial cancer cells subcutaneously in the right flank. After tumors were at least 3–5 mm in diameter, treatment with control, metformin 100 mg/kg, or metformin 200 mg/kg was started. Mice were sacrificed after 4 weeks of treatment. <b>A</b>. Tumor weight (in grams) from the mice with the 3 largest tumors in each group. <b>B</b>. Average body weight (g) of the mice in each group at conclusion of the study. <b>C</b>. Western blot results of STAT3 and associated proteins after treatment with control, 100 mg/kg, or 200 mg/kg of metformin.</p

Metformin inhibits STAT3, its regulatory proteins and upregulated apoptosis-related proteins, in grade 1 endometrial cancer cells.

<p><b>A</b>. Western blot of STAT3 and its regulatory proteins in Ishikawa cells after treatment with control, 10 mM, or 20 mM metformin for 48h in high-glucose conditions. <b>B</b>. qPCR of STAT3 and some of its regulatory genes in Ishikawa cells after treatment with control, 10 mM, or 20 mM metformin for 48h. Groups significantly different than control (p<0.05) are indicated with an asterisk (*). <b>C</b>. Metformin did not affects pSTAT3 and STAT3 in normal glucose conditions.</p

Metformin inhibits grade 1 endometrial cancer cell proliferation, survival, migration, and induces apoptosis.

<p><b>A</b>. Sulforhodamine B (SRB) assay measured Ishikawa cell proliferation with increasing concentrations of metformin after 24h or 48h, in high-glucose media. <b>B</b>. Proportion of Ishikawa cells surviving (compared to control) after treatment with 10 mM or 20 mM of metformin. <b>C</b>. Cell migration assay, with Ishikawa cells subjected to control, 10 mM, or 20 mM metformin for 24h. Control (0h) is also shown. <b>D</b>. Quantification of % wound closure; the 10 mM and 20 mM treatment groups were each significantly different than control (p<0.05; noted with asterisk [*]). <b>E</b>. Western blot of apoptosis-related protein expression in Ishikawa cells after treatment with control, 10 mM, or 20 mM for 48h.</p