A study of elective genome sequencing and pharmacogenetic testing in an unselected population

BACKGROUND: Genome sequencing (GS) of individuals without a medical indication, known as elective GS, is now available at a number of centers around the United States. Here we report the results of elective GS and pharmacogenetic panel testing in 52 individuals at a private genomics clinic in Alabama. METHODS: Individuals seeking elective genomic testing and pharmacogenetic testing were recruited through a private genomics clinic in Huntsville, AL. Individuals underwent clinical genome sequencing with a separate pharmacogenetic testing panel. RESULTS: Six participants (11.5%) had pathogenic or likely pathogenic variants that may explain one or more aspects of their medical history. Ten participants (19%) had variants that altered the risk of disease in the future, including two individuals with clonal hematopoiesis of indeterminate potential. Forty-four participants (85%) were carriers of a recessive or X-linked disorder. All individuals with pharmacogenetic testing had variants that affected current and/or future medications. CONCLUSION: Our study highlights the importance of collecting detailed phenotype information to interpret results in elective GS

Postpartum Prolapsed Leiomyoma with Uterine Inversion Managed by Vaginal Hysterectomy

Background. Uterine inversion is a rare, but life threatening, obstetrical emergency which occurs when the uterine fundus collapses into the endometrial cavity. Various conservative and surgical therapies have been outlined in the literature for the management of uterine inversions. Case. We present a case of a chronic, recurrent uterine inversion, which was diagnosed following spontaneous vaginal delivery and recurred seven weeks later. The uterine inversion was likely due to a leiomyoma. This late-presenting, chronic, recurring uterine inversion was treated with a vaginal hysterectomy. Conclusion. Uterine inversions can occur in both acute and chronic phases. Persistent vaginal bleeding with the appearance of a prolapsing fibroid should prompt further investigation for uterine inversion and may require surgical therapy. A vaginal hysterectomy may be an appropriate management option in select populations and may be considered in women who do not desire to maintain reproductive function

Identification of cytosolic phosphodiesterases in the erythrocyte: A possible role for PDE5

Background Within erythrocytes (RBCs), cAMP levels are regulated by phosphodiesterases (PDEs). Increases in cAMP and ATP release associated with activation of β-adrenergic receptors (βARs) and prostacyclin receptors (IPRs) are regulated by PDEs 2, 4 and PDE 3, respectively. Here we establish the presence of cytosolic PDEs in RBCs and determine a role for PDE5 in regulating levels of cGMP. Material/Methods Purified cytosolic proteins were obtained from isolated human RBCs and western analysis was performed using antibodies against PDEs 3A, 4 and 5. Rabbit RBCs were incubated with dbcGMP, a cGMP analog, to determine the effect of cGMP on cAMP levels. To determine if cGMP affects receptor-mediated increases in cAMP, rabbit RBCs were incubated with dbcGMP prior to addition of isoproterenol (ISO), a βAR receptor agonist. To demonstrate that endogenous cGMP produces the same effect, rabbit and human RBCs were incubated with SpNONOate (SpNO), a nitric oxide donor, and YC1, a direct activator of soluble guanylyl cyclase (sGC), in the absence and presence of a selective PDE5 inhibitor, zaprinast (ZAP). Results Western analysis identified PDEs 3A, 4D and 5A. dbcGMP produced a concentration dependent increase in cAMP and ISO-induced increases in cAMP were potentiated by dbcGMP. In addition, incubation with YC1 and SpNO in the presence of ZAP potentiated βAR-induced increases in cAMP. Conclusions PDEs 2, 3A and 5 are present in the cytosol of human RBCs. PDE5 activity in RBCs regulates cGMP levels. Increases in intracellular cGMP augment cAMP levels. These studies suggest a novel role for PDE5 in erythrocytes

RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma.

Activating mutations in KRAS occur in 32% of lung adenocarcinomas (LUAD). Despite leading to aggressive disease and resistance to therapy in preclinical studies, the KRAS mutation does not predict patient outcome or response to treatment, presumably due to additional events modulating RAS pathways. To obtain a broader measure of RAS pathway activation, we developed RAS84, a transcriptional signature optimised to capture RAS oncogenic activity in LUAD. We report evidence of RAS pathway oncogenic activation in 84% of LUAD, including 65% KRAS wild-type tumours, falling into four groups characterised by coincident alteration of STK11/LKB1, TP53 or CDKN2A, suggesting that the classifications developed when considering only KRAS mutant tumours have significance in a broader cohort of patients. Critically, high RAS activity patient groups show adverse clinical outcome and reduced response to chemotherapy. Patient stratification using oncogenic RAS transcriptional activity instead of genetic alterations could ultimately assist in clinical decision-making

Improved respiratory motion tracking through a novel fiducial marker placement guidance system during electromagnetic navigational bronchoscopy (ENB)

Background: Stereotactic ablative radiotherapy (SABR) is a treatment option for patients with early stage non-small cell lung cancer (NSCLC) and recurrent or oligometastatic disease who are not surgical candidates. Due to the continuous motion of tumors within the lungs, implementing a strategy to track the target lesion is crucial. One method is to place fiducial markers which the robotic SABR system is able to track during treatment. However, placing these markers in a manner that maximizes tracking efficacy can be challenging. Using a novel fiducial placement guidance system (FPGS) during fiducial deployment may offer a way to improve the quantity of fiducials tracked by the robotic SABR system. Method: This was an institutional, retrospective review identifying all patients who received robotic SABR for lung tumors from May 2015 until January 2017. The FPGS was instituted in May 2016. The median number of fiducials tracked and the rate of complication was compared between patients whose fiducials were placed using FPGS versus those that were not. Results: A total of 128 patients with 147 treated lung lesions were identified. Of the lesions that utilized FPGS (n = 44), 28 had 2 tracked fiducials (63.6%), 14 had 3 (31.8%) and 2 had 4 (4.6%). Of the lesions treated without FPGS (n = 103), 5 had 1 tracked fiducial (4.9%), 91 had 2 (88.4%), 6 had 3 (5.8%), and 2 had 4 (1.9%). A significant improvement in the median number of fiducials tracked per fraction was observed for the lesions with fiducials placed using FPGS on Wilcoxon rank sum test (p < 0.001). The rate of complication was low and not statistically different between cohorts (p = 0.44). Conclusions: The FPGS can be used during the deployment of fiducial markers and may increase the number of fiducials tracked

The Promise and Realities of the Use of Cyber Technologies for Promoting Research in Public STEM Museum Experiences

Cyberlab at OSU Final Report.A seven-year effort funded by the United States’ National Science Foundation and the Oregon Sea Grant College Program sought to identify and deploy in a public STEM museum setting a suite of digital tools for collecting and supporting analysis of data on the use of the setting in near real time and as evidence for in situ learning. In addition to full-museum camera coverage and data collection, five exhibit-based research platforms were developed to allow for collection of linked video, audio, and digital input (keystroke, touch screen manipulation) data at particular locations in the museum. A further effort explored the use of social media data mining tools as well as apps for research on how learners create continuity across STEM learning experiences distributed temporally and geographically. Returns on investment for research on informal learning were proven to be high with signifiant gains for researchers working with the museum and for building research partnerships with other museums and informal STEM learning environments (e.g., Maker Faires, public exhibits, tourism in marine environments), but return on investment for museum operations and programmatic advancement were relatively minor. While the project proved that a public museum can successfully employ current video-based, cyber-linked technologies to document and study learning outside of a laboratory setting, it also demonstrated that such activity is most likely beyond the budgetary and information technology capacity of most public institutions. However, the project also piloted and provided proof of concept for smaller, mobile efforts using many of the same technologies and tools in scaled-down but efficient research and evaluation efforts.Keywords: Cyberlearning; Informal Learning Environments; STEM; Video-based Researc

Farmers’ market use is associated with fruit and vegetable consumption in diverse southern rural communities

Background While farmers’ markets are a potential strategy to increase access to fruits and vegetables in rural areas, more information is needed regarding use of farmers’ markets among rural residents. Thus, this study’s purpose was to examine (1) socio-demographic characteristics of participants; (2) barriers and facilitators to farmers’ market shopping in southern rural communities; and (3) associations between farmers’ market use with fruit and vegetable consumption and body mass index (BMI). Methods Cross-sectional surveys were conducted with a purposive sample of farmers’ market customers and a representative sample of primary household food shoppers in eastern North Carolina (NC) and the Appalachian region of Kentucky (KY). Customers were interviewed using an intercept survey instrument at farmers’ markets. Representative samples of primary food shoppers were identified via random digit dial (RDD) cellular phone and landline methods in counties that had at least one farmers’ market. All questionnaires assessed socio-demographic characteristics, food shopping patterns, barriers to and facilitators of farmers’ market shopping, fruit and vegetable consumption and self-reported height and weight. The main outcome measures were fruit and vegetable consumption and BMI. Descriptive statistics were used to examine socio-demographic characteristics, food shopping patterns, and barriers and facilitators to farmers’ market shopping. Linear regression analyses were used to examine associations between farmers’ market use with fruit and vegetable consumption and BMI, controlling for age, race, education, and gender. Results Among farmers’ market customers, 44% and 55% (NC and KY customers, respectively) reported shopping at a farmers’ market at least weekly, compared to 16% and 18% of NC and KY RDD respondents. Frequently reported barriers to farmers’ market shopping were market days and hours, “only come when I need something�, extreme weather, and market location. Among the KY farmers’ market customers and NC and KY RDD respondents, fruit and vegetable consumption was positively associated with use of farmers’ markets. There were no associations between use of farmers’ markets and BMI. Conclusions Fruit and vegetable consumption was associated with farmers’ market shopping. Thus, farmers’ markets may be a viable method to increase population-level produce consumption

Bangladeshi women's experiences of infant feeding in the London Borough of Tower Hamlets.

This study examined the main factors that influence Bangladeshi women living in London's decisions to partially breastfeed their children, including the influence of older women within the community. Fifty-seven women of Bangladeshi origin living in the London Borough of Tower Hamlets took part in seven discussion groups between April and June 2013. Five groups were held with women of child-bearing age and two groups with older women in the community. A further eight younger women and three older women took part in one-on-one interviews. Interviews were also carried out with eight local health care workers, including public health specialists, peer support workers, breastfeeding coordinators and a health visitor. The influences on women's infant feeding choices can be understood through a 'socio-ecological model', including public health policy; diverse cultural influences from Bangladesh, London and the Bangladeshi community in London; and the impacts of migration and religious and family beliefs. The women's commitment to breastfeeding was mediated through the complexity of their everyday lives. The tension between what was 'best' and what was 'possible' leads them not only to partially breastfeed but also to sustain partial breastfeeding in a way not seen in other socio-cultural groups in the United Kingdom

Nursing Care for Pregnant Adolescents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73476/1/0884217503252191.pd

Tumour-suppression function of KLF12 through regulation of anoikis

Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell adhesion. Knockdown of KLF12 in parental cells results in decreased apoptosis following cell detachment from matrix. KLF12 regulates anoikis by promoting the cell cycle transition through S phase and therefore cell proliferation. Reduced expression levels of KLF12 results in increased ability of lung cancer cells to form tumours in vivo and is associated with poorer survival in lung cancer patients. We therefore identify KLF12 as a novel metastasis-suppressor gene whose loss of function is associated with anoikis resistance through control of the cell cycle