Gestational Diabetes and Its Effects on the Fetus

Although the common effects of gestational diabetes on the fetus are known, the outcome of a diabetic gestation is ambiguous. There is concern for complications in the fetus at delivery due to enlarged size of the fetus, as well as concerns for birth defects, fetal distress, diabetes and obesity. Yet, although there is a correlation in the previous disorders and gestational diabetes, many of the mechanisms that cause these complications are unknown. By studying the pathology of gestational diabetes, researchers have learnt that the placenta controls fetal growth and provides a great deal of protection for the fetus. Therefore, many of the effects of diabetes are masked by the placenta. The problems that arise from gestational diabetes are often the result of a subtle disturbance of the fetuses’ metabolism or from some obstruction of the placenta’s ability to protect the fetus. Therefore, to properly understand the effects of gestational diabetes, it is necessary to know not only the effects of diabetes but also the mechanics of the placenta, the changes it undergoes during gestational diabetes and the effects of these changes on the fetus

Shifting Gear: A Historical Analysis of the Use of Supportive Apparel in Powerlifting

In many ways, powerlifting is an odd sport. Competitors do not run or jump; no balls, bats, or rackets are used; and only one competitor plays on the lifting platform at a time. Judging can be highly subjective; three judges intently watch as the athlete lifts the loaded barbell nine separate times over the course of the competition. There is no instant replay and most lifts take less than ten seconds to perform. At the end of the lift, each judge throws a switch; if at least two white lights appear, the lift is good; if two or more lights are red, the lift does not count. Three squats, three bench presses, and three deadlifts constitute the nine attempts of a powerlifting contest. At most, lifters spend ninety seconds competing during what is generally a day-long contest

Weighing the Options: Conversations on the Use of Performance Enhancing Gear in Powerlifting

The subject of supportive gear in powerlifting has been controversial from the earliest days in the sport. While our article Shifting Gear, also in this issue, provides an historical overview of the use of powerlifting gear, we came to believe as we were working on it that including the voices of active and retired powerlifters would broaden our understanding of this debate. Accordingly, we interviewed a number of individuals with different backgrounds in the sport in order to explore their attitudes and experiences with gear. Our hope is that their thoughts on this important topic will help readers develop a more nuanced understanding of the issue, and that even those well-versed in the sport may find a fresh perspective.1 This essay is not intended to provide an unequivocal answer, or solution to the gear debate. Our hope, however, is that it enriches the previous piece by providing more perspectives, and demonstrates the complexity of the issue for active lifters

A comparative study of fragment screening methods on the p38α kinase: new methods, new insights

The stress-activated kinase p38α was used to evaluate a fragment-based drug discovery approach using the BioFocus fragment library. Compounds were screened by surface plasmon resonance (SPR) on a Biacore(™) T100 against p38α and two selectivity targets. A sub-set of our library was the focus of detailed follow-up analyses that included hit confirmation, affinity determination on 24 confirmed, selective hits and competition assays of these hits with respect to a known ATP binding site inhibitor. In addition, functional activity against p38α was assessed in a biochemical assay using a mobility shift platform (LC3000, Caliper LifeSciences). A selection of fragments was also evaluated using fluorescence lifetime (FLEXYTE(™)) and microscale thermophoresis (Nanotemper) technologies. A good correlation between the data for the different assays was found. Crystal structures were solved for four of the small molecules complexed to p38α. Interestingly, as determined both by X-ray analysis and SPR competition experiments, three of the complexes involved the fragment at the ATP binding site, while the fourth compound bound in a distal site that may offer potential as a novel drug target site. A first round of optimization around the remotely bound fragment has led to the identification of a series of triazole-containing compounds. This approach could form the basis for developing novel and active p38α inhibitors. More broadly, it illustrates the power of combining a range of biophysical and biochemical techniques to the discovery of fragments that facilitate the development of novel modulators of kinase and other drug targets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10822-011-9454-9) contains supplementary material, which is available to authorized users

DPOAEs in Children With Sickle Cell Disease

The purpose of this study was to investigate distortion product otoacoustic emissions (DPOAEs) in young normal-hearing children with sickle cell disease (SCD). It was hypothesized that the prevalence of DPOAEs and response amplitudes would be lower than those in children with normal hemoglobin due to suspected compromised cochlear function as a result of vaso-occlusive events characteristic of SCD. Twenty African-American children with SCD and 15 African-American children with normal hemoglobin participated. Distortion product OAEs were evoked by thirteen primary tone pairs with f2 frequencies ranging from 1000 to 4500 Hz. The primary tones were presented at and L1 and L2 levels of 70 and 60 dB SPL (high) and 50 and 40 dB SPL (low), respectively. The findings of this study were completely unexpected and contrary to our original hypotheses. The likelihood of detecting a DPOAE response was not related to the clinical status of the children. Distortion product OAE amplitudes were significantly larger for children with SCD (p = .01). Educational Objectives: After completing this article the reader will (1) have a basic knowledge of the audiometric complications of sickle cell disease and (2) appreciate the differences in DPOAEs between young normal-hearing children with sickle cell DPOAEs in Children With Sickle Cell Disease 3 disease and young normal-hearing children with normal hemoglobin

The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance

The maintenance of immune tolerance requires the deletion of self-reactive T cells in the thymus. The expression of tissue-specific antigen genes (TSAs) by thymic epithelial cells is critical for this process and depends on the activity of the Autoimmune Regulator (Aire) protein, however, the molecular mechanism(s) Aire uses to target TSA gene loci are unknown. Here we identified two Aire-interacting proteins – activating transcription factor 7 interacting protein (ATF7ip) and methyl CpG binding protein 1 (MBD1) –that are required for Aire’s targeting of TSA geneloci. Moreover, Mbd1−/− mice developed pathological autoimmunity and had a defect in Aire-dependent thymic TSA gene expression underscoring the critical importance of Aire’s interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance

Undergraduate Medical Education Reform in Viet Nam for a Primary Health Care Workforce

Strong primary health care (PHC) systems require a robust PHC workforce. Traditionally, medical education takes place in academic medical centres that favour subspecialty care rather than PHC settings. This may undervalue primary care as a career and contribute to a shortage of PHC workers. However, designing undergraduate medical education curricula that incorporate early experiences in clinical care delivery at PHC sites remains a challenge, including in many low- and middle-income countries (LMICs). This paper describes how a collaboration between Harvard Medical School and five medical schools in Vietnam, and in-country collaborations among the Vietnamese medical schools, facilitated curricular innovation and co-creation of coursework relevant to PHC through the development of a Practice of Medicine (POM) course. The collaboration implemented a technical assistance strategy consisting of in-person workshops, focused virtual consultations, on-site ‘office hours’, site visits and observations to each of the five medical universities, and immersion trips to support the creation and implementation of the POM course. A pilot program was started at a single site and then scaled nationally using local customisation, experience, and expertise utilising a train-the-trainers approach. As a result, five new POM courses have been developed by five Vietnamese institutions. Fifty Vietnamese faculty received training to lead the POM course development, and 228 community-based preceptors have been trained to teach students at PHC sites. A total of 52 new PHC and community-based clinical training sites have been added, and 3,615 students have completed or are currently going through a POM course. This experience can serve as a model for future academic collaborations to support the development of a robust PHC workforce for the 21st century

Attributes of legitimate venture failure impressions

The current research investigates the effectiveness of impression management strategies available to entrepreneurs to foster social legitimacy with stakeholders following venture failure. We use a conjoint experiment to examine how different attributions of causes of failure influence the general public's legitimacy judgments. The most effective strategy proves to be the entrepreneurs distancing themselves from the failure, in that they attribute the failure to external factors that are not under the entrepreneurs' volitional control, and brought about by circumstances that are unlikely to reoccur. Our analysis also considers how the audience members' dispositional agreeableness and general self-efficacy influence judgment formation