Twenty Years of the Ryan Residency Training Program in Abortion and Family Planning

ObjectiveTo summarize the effects of routine, opt-out abortion and family planning residency training on obstetrics and gynecology (ob-gyn) residents’ clinical skills in uterine evacuation and intentions to provide abortion care after residency.MethodsData from ob-gyn residency programs supported during the first 20 years of the Kenneth J. Ryan Residency Training Program in Abortion and Family Planning were analyzed. Postrotation surveys assessed residents’ training experiences and acquisition of abortion care skills. Residency program director surveys assessed benefits of the training to residents and the academic department from the educators’ perspectives.ResultsA total of 2775 residents in 89 ob-gyn programs completed postrotation surveys for a response rate of 72%. During the rotation, residents – including those who only partially participated – gained exposure to and skills in first- and second-trimester abortion care. Sixty-one percent intended to provide abortion care in their postresidency practice. More than 90% of residency program directors (97.5% response rate) reported that training improved resident competence in abortion and contraception care and 81.3% reported that the training increased their own program's appeal to residency applicants.ConclusionOver 20 years, the Ryan Program has supported programs to integrate abortion training to give ob-gyn residents the skills and inspiration to provide comprehensive reproductive health care, including uterine evacuation and abortion care, in future practice. Residency program directors noted that this integrated training meets resident applicants’ expectations.ImplicationsRyan Program residents are trained to competence and are prepared, both clinically and in their professional attitudes, to care for women's reproductive health.     

Monkey Bites among US Military Members, Afghanistan, 2011

Bites from Macaca mulatta monkeys, native to Afghanistan, can cause serious infections. To determine risk for US military members in Afghanistan, we reviewed records for September–December 2011. Among 126 animal bites and exposures, 10 were monkey bites. Command emphasis is vital for preventing monkey bites; provider training and bite reporting promote postexposure treatment.     

Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats

Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified.     

Temperature dependence of protein motions in a thermophilic dihydrofolate reductase and its relationship to catalytic efficiency

We report hydrogen deuterium exchange by mass spectrometry (HDX-MS) as a function of temperature in a thermophilic dihydrofolate reductase from Bacillus stearothermophilus (Bs-DHFR). Protein stability, probed with circular dichroism, established an accessible temperature range of 10 °C to 55 °C for the interrogation of HDX-MS. Although both the rate and extent of HDX are sensitive to temperature, the majority of peptides showed rapid kinetics of exchange, allowing us to focus on plateau values for the maximal extent of exchange at each temperature. Arrhenius plots of the ratio of hydrogens exchanged at 5 h normalized to the number of exchangeable hydrogens vs. 1/T provides an estimate for the apparent enthalpic change of local unfolding, ΔH°_unf(avg). Most regions in the enzyme show ΔH°_unf(avg) ≤ 2.0 kcal/mol, close to the value of kT; by contrast, significantly elevated values for ΔH°_unf(avg) are observed in regions within the core of protein that contain the cofactor and substrate-binding sites. Our technique introduces a new strategy for probing the temperature dependence of local protein unfolding within native proteins. These findings are discussed in the context of the demonstrated role for nuclear tunneling in hydride transfer from NADPH to dihydrofolate, and relate the observed enthalpic changes to two classes of motion, preorganization and reorganization, that have been proposed to control the efficiency of hydrogenic wave function overlap. Our findings suggest that the enthalpic contribution to the heavy atom environmental reorganizations controlling the hydrogenic wave function overlap will be dominated by regions of the protein proximal to the bound cofactor and substrate.     

PRKDC mutations in a SCID patient with profound neurological abnormalities

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs; encoded by PRKDC) functions in DNA non-homologous end-joining (NHEJ), the major DNA double strand break (DSB) rejoining pathway. NHEJ also functions during lymphocyte development, joining V(D)J recombination intermediates during antigen receptor gene assembly. Here, we describe a patient with compound heterozygous mutations in PRKDC, low DNA-PKcs expression, barely detectable DNA-PK kinase activity, and impaired DSB repair. In a heterologous expression system, we found that one of the PRKDC mutations inactivated DNA-PKcs, while the other resulted in dramatically diminished but detectable residual function. The patient suffered SCID with reduced or absent T and B cells, as predicted from PRKDC-deficient animal models. Unexpectedly, the patient was also dysmorphic; showed severe growth failure, microcephaly, and seizures; and had profound, globally impaired neurological function. MRI scans revealed microcephaly-associated cortical and hippocampal dysplasia and progressive atrophy over 2 years of life. These neurological features were markedly more severe than those observed in patients with deficiencies in other NHEJ proteins. Although loss of DNA-PKcs in mice, dogs, and horses was previously shown not to impair neuronal development, our findings demonstrate a stringent requirement for DNA-PKcs during human neuronal development and suggest that high DNA-PK protein expression is required to sustain efficient pre- and postnatal neurogenesis.     

The prediction of short-stay psychiatric inpatients

In a study of 252 consecutive, non-repeating psychiatric admissions at a community hospital, patients who were hospitalized for six days or less were identified. Using the Severity of Psychiatric Illness, these cases were predicted with both a sensitivity and specificity of about 75 %. Short-stay patients were more acutely suicidal, had greater substance abuse complications, tended to be resistant to the treatment program, and had lower levels of family involvement. Programming and policy implications of these findings are discussed.The contents of this paper were developed under a grant from the National Institute of Disability and Rehabilitation Research, Department of Education cooperative agreement number H13B00011, and the National Institutes of Health. The contents do not necessarily reflect the views of the NIH, and do not imply endorsement by the U.S. government.     

A micropatterning and image processing approach to simplify measurement of cellular traction forces

Quantification of the traction forces that cells apply to their surroundings has been critical to the advancement of our understanding of cancer, development and basic cell biology. This field was made possible through the development of engineered cell culture systems that permit optical measurement of cell-mediated displacements and computational algorithms that allow conversion of these displacements into stresses and forces. Here, we present a novel advancement of traction force microscopy on polyacrylamide (PAA) gels that addresses limitations of existing technologies. Through an indirect patterning technique, we generated PAA gels with fluorescent 1 μm dot markers in a regularized array. This improves existing traction measurements since (i) multiple fields of view can be measured in one experiment without the need for cell removal; (ii) traction vectors are modeled as discrete point forces, and not as a continuous field, using an extremely simple computational algorithm that we have made available online; and (iii) the pattern transfer technique is amenable to any of the published techniques for producing patterns on glass. In the future, this technique will be used for measuring traction forces on complex patterns with multiple, spatially distinct ligands in systems for applying strain to the substrate, and in sandwich cultures that generate quasi-three-dimensional environments for cells.     

Effects of handling during infancy on the sympathetic–adrenal medullary system of rats

We examined the effects of daily handling and maternal separation (5 min per day) on the responsiveness of the sympathetic-adrenal medullary system of Sprague-Dawley rats before weaning and in adulthood. Plasma levels of norepinephrine (derived primarily from sympathetic nerves) and epinephrine (released from the adrenal medulla) were elevated in handled pups compared to unhandled controls at 14 and 18 days of age but not at 6 and 10 days of age. When tested in adulthood, previously handled and control rats did not differ with respect to basal or stress-induced increments in plasma levels of norepinephrine and epinephrine. These results indicate that brief daily episodes of handling and maternal separation are attended by an increase in sympathetic-adrenal medullary tone in 14–18-day-old rats. However, the enhanced response of the sympathetic–adrenal medullary system of separated rats may not persist into adulthood.