The Roles of PPARs in the Fetal Origins of Metabolic Health and Disease

Beyond the short-term effects on fertility, there is increasing evidence that obesity or the consumption of an inappropriate diet by the mother during pregnancy adversely affects the long-term health of her offspring. PPAR and RXR isotypes are widely expressed in reproductive tissues and in the developing fetus. Through their interactions with fatty acids, they may mediate adaptive responses to the changes in the maternal diet. In the maturing follicle, PPAR-γ has an important role in the granulosa cells that surround the maturing oocyte. After fertilisation, PPAR-γ and PPAR-β/δ are essential regulators of placentation and the subsequent development of key metabolic tissues such as skeletal muscle and adipose cells. Activation of PPAR-γ and PPAR-β/δ during fetal development has the potential to modify the growth and development of these tissues. PPAR-α is expressed at low levels in the fetal liver, however, this expression may be important, as changes in the methylation of DNA in its promoter region are reported to take place during this period of development. This epigenetic modification then programmes subsequent expression. These findings suggest that two separate PPAR-dependent mechanisms may be involved in the fetal adaptations to the maternal diet, one, mediated by PPAR-γ and PPAR-β/δ, regulating cell growth and differentiation; and another adapting long-term lipid metabolism via epigenetic changes in PPAR-α to optimise postnatal survival

Improved Ice Cloud Representation In The Community Aerosol and Radiation Model For Atmospheres (CARMA) Cirrus Cloud Model In CESM1

Cirrus clouds are an important feature in Earth&rsquo;s climate system making a proper representation of cirrus clouds a necessity in general circulation models (GCM&rsquo;s). The primary focus of this thesis is to improve the representation of ice clouds in version 5 of the Community Atmosphere Model (CAM5), which is coupled to the Community Aerosol and Radiation Model for Atmosphere (CARMA) sectional ice microphysical model introduced by Bardeen et al. (2013). Over the course of this PhD work, one published study using the CARMA model was made, and another study was prepared for publication. Aircraft and satellite observations were used to evaluate simulations of cirrus in both studies. In the first study simulations of tropical tropopause layer (TTL) cirrus clouds in the standard CAM5 model and in the coupled CAM5/CARMA model were found to underrepresent observed cloud frequency, in-cloud ice size distributions, and relative humidity in the TTL. In response, we present a modified ice cloud fraction scheme which boosts TTL cloud fraction. Due to coarse vertical model resolution in the TTL, we also prescribe a 2 K decrease in cold point tropopause temperatures to better align with observations. Our modifications improve both CAM5 and CAM5/CARMA&rsquo;s in-cloud ice size and mass distributions. However, only CAM5/CARMA has a significant improvement in cloud frequency and relative humidity. The second study implemented a correction to the wet removal of aerosols within convection first proposed by (Yu et al., 2019). Interactive sulfates for ice nucleation and a heterogeneous nucleation parameterization were also added to CARMA. Both use aerosols provided by the Modal Aerosol Model (MAM). Simulations showed that these modifications improved dust and sulfate distributions in the CAM5/CARMA model. Though IN amount was improved, high ice cloud fraction (P &lt; 440 hPa) and longwave cloud forcing remained insensitive to these changes. However, ice water path, in-cloud ice water content, and ice crystal effective radius all were noticeably improved when compared to observations. Most of these improvements occurred at latitudes poleward of 30o and at mid-troposphere levels. Overall, the modifications conducted over the course of this thesis improved ice cloud representation in the CAM5/CARMA GCM.</p

146 - Localization of Sonic Hedgehog (Shh) Protein in Zebrafish

Zebrafish possess a unique ability to regenerate their retina when damaged; our objective is to gain a better understanding regarding retinal regeneration in zebrafish in hopes of eventually utilizing this information to promote retinal regeneration in humans. It has been shown that a protein, Sonic Hedgehog signaling protein (shh), plays a role in the differentiation of progenitor cells during eye development in zebrafish. Researchers have concluded that shh moves across the retina in a wave-like fashion during vertebrate development and regeneration. Studies have been conducted to see how the shh protein moves, but none have investigated the exact location that shh binds. We want to localize the shh protein in zebrafish during regeneration. Techniques such as immunohistochemistry, antigen retrieval and colocalization were used. Anti-Glutamine synthetase and anti-Glial fibrillary acidic protein were the antibodies used during these techniques to assess whether or not the shh is associated with müler glia cells in the retina. Our confocal microscope pictures depict promising localization information to see which specific cells Shh is associated with

Microbial Activity of Soil Following Steam Treatment

The effect of steam treatment on subsurface aerobic and anaerobic microbial communities was investigated using multiple microbial assays. Soil samples were gathered and analyzed prior to, one month after, and eight months after a five-month field pilot test of steam injection and extraction. Aerobic soil samples were analyzed by respirometry, plate counts, and direct microscopic counts. Anaerobic microbial activity was examined by monitoring methane generation in anaerobic microcosms with gas chromatography. Respirometry showed pre-steam CO2 production was consistent with natural attenuation, post-steam (one month) CO2 production was below detection, and post-steam (eight months) CO2 production was about half of pre-steam. Post-steam (one and eight month) plate counts were one to four orders of magnitude lower than the pre-steam samples. Direct microscopic counts showed post-steam (one and eight month) cell numbers were higher than the pre-steam counts, but based on plate counts these cells were mostly non-viable. Significant amounts of methane and hydrogen were generated from pre-steam anaerobic microcosms, but post-steam microcosms had no detectable methane, and only trace amounts of hydrogen. Terminal restriction fragment (TRF) analysis was performed to determine the diversity of the microbial community before and after steam treatment. Pre-steam TRF analysis showed distinct differences in the microbial communities above and below the smear zone. Post-steam TRF analyses were not possible because insufficient DNA could be extracted from the soil

Safety of overlapping inpatient orthopaedic surgery: A multicenter study

BackgroundAlthough overlapping surgery is used to maximize efficiency, more empirical data are needed to guide patient safety. We conducted a retrospective cohort study to evaluate the safety of overlapping inpatient orthopaedic surgery, as judged by the occurrence of perioperative complications.MethodsAll inpatient orthopaedic surgical procedures performed at 5 academic institutions from January 1, 2015, to December 31, 2015, were included. Overlapping surgery was defined as 2 skin incisions open simultaneously for 1 surgeon. In comparing patients who underwent overlapping surgery with those who underwent non-overlapping surgery, the primary outcome was the occurrence of a perioperative complication within 30 days of the surgical procedure, and secondary outcomes included all-cause 30-day readmission, length of stay, and mortality. To determine if there was an association between overlapping surgery and a perioperative complication, we tested for non-inferiority of overlapping surgery, assuming a null hypothesis of an increased risk of 50%. We used an inverse probability of treatment weighted regression model adjusted for institution, procedure type, demographic characteristics (age, sex, race, comorbidities), admission type, admission severity of illness, and clustering by surgeon.ResultsAmong 14,135 cases, the frequency of overlapping surgery was 40%. The frequencies of perioperative complications were 1% in the overlapping surgery group and 2% in the non-overlapping surgery group. The overlapping surgery group was non-inferior to the non-overlapping surgery group (odds ratio [OR], 0.61 [90% confidence interval (CI), 0.45 to 0.83]; p &lt; 0.001), with reduced odds of perioperative complications (OR, 0.61 [95% CI, 0.43 to 0.88]; p = 0.009). For secondary outcomes, there was a significantly lower chance of all-cause 30-day readmission in the overlapping surgery group (OR, 0.67 [95% CI, 0.52 to 0.87]; p = 0.003) and shorter length of stay (e, 0.94 [95% CI, 0.89 to 0.99]; p = 0.012). There was no difference in mortality.ConclusionsOur results suggest that overlapping inpatient orthopaedic surgery does not introduce additional perioperative risk for the complications that we evaluated. The suitability of this practice should be determined by individual surgeons on a case-by-case basis with appropriate informed consent.Level of evidenceTherapeutic Level III. See Instructions for Authors for a complete description of levels of evidence

ASCA Observation of an X-Ray-Luminous Active Nucleus in Markarian 231

We have obtained a moderately long (100 kilosecond) ASCA observation of the Seyfert 1 galaxy Markarian 231, the most luminous of the local ultraluminous infrared galaxy (ULIRG) population. In the best-fitting model we do not see the X-ray source directly; the spectrum consists of a scattered power-law component and a reflection component, both of which have been absorbed by a column N_H \approx 3 X 10^(22)/cm^2. About 3/4 of the observed hard X-rays arise from the scattered component, reducing the equivalent width of the iron K alpha line. The implied ratio of 1-10 keV X-ray luminosity to bolometric luminosity, L_x/L_bol \sim 2%, is typical of Sy 1 galaxies and radio-quiet QSOs of comparable bolometric luminosities, and indicates that the bolometric luminosity is dominated by the AGN. Our estimate of the X-ray luminosity also moves Mrk 231 in line with the correlations found for AGN with extremely strong Fe II emission. A second source separated by about 2 arcminutes is also clearly detected, and contributes about 25% of the total flux.Comment: 11 pages, 3 figures; to appear in ApJ Letter

Comparison of Patient Reported Outcomes using PROMIS in Patients with Shoulder Pain

Objectives: Compare a disease specific questionnaire (American Shoulder and Elbow Surgeons [ASES]) and a multidimensional global health scale (Patient reported outcome measurement system [PROMIS]) across a variety of shoulder condition

Erythroid Kruppel-like factor directly activates the basic Kruppel-like factor gene in erythroid cells

The Sp/Kriippel-like factor (Sp/KIf) family is comprised of around 25 zinc finger transcription factors that recognize CACCC boxes and GC-rich elements. We have investigated basic Kruppel-like factor (Bklf/Klf3) and show that in erythroid tissues its expression is highly dependent on another family member, erythroid Kruppel-like factor (Eklf/Kif1). We observe that Bklf mRNA is significantly reduced in erythroid tissues from Eklf-null murine embryos. We find that Bklf is driven primarily by two promoters, a ubiquitously active GC-rich upstream promoter, la, and an erythroid downstream promoter, 1b. Transcripts from the two promoters encode identical proteins. Interestingly, both the ubiquitous and the erythroid promoter are dependent on Eklf in erythroid cells. Eklf also activates both promoters in transient assays. Experiments utilizing an inducible form of Eklf demonstrate activation of the endogenous Bklf gene in the presence of an inhibitor of protein synthesis. The kinetics of activation are also consistent with Bklf being a direct Eklf target. Chromatin immunoprecipitation assays confirm that Eklf associates with both Bklf promoters. Eklf is typically an activator of transcription, whereas Bklf is noted as a repressor. Our results support the hypothesis that feedback cross-regulation occurs within the Sp/Klf family in vivo

How High? Trends in Cannabis Use Prior to First Admission to Inpatient Psychiatry in Ontario, Canada, between 2007 and 2017

Objectives: To examine the trends in cannabis use within 30 days of first admission to inpatient psychiatry in Ontario, Canada, between 2007 and 2017, and the characteristics of persons reporting cannabis use. Methods: A retrospective cross-sectional analysis was conducted for first-time admissions to nonforensic inpatient psychiatric beds in Ontario, Canada, between January 1, 2007, and December 31, 2017, using data from the Ontario Mental Health Reporting System (N = 81,809). Results: Across all years, 20.1% of patients reported cannabis use within 30 days of first admission. Use increased from 16.7% in 2007 to 25.9% in 2017, and the proportion with cannabis use disorders increased from 3.8% to 6.0%. In 2017, 47.9% of patients aged 18 to 24 and 39.2% aged 25 to 34 used cannabis, representing absolute increases of 8.3% and 10.7%, respectively. Increases in cannabis use were found across almost all diagnostic groups, with the largest increases among patients with personality disorders (15% increase), schizophrenia or other psychotic disorders (14% increase), and substance use disorders (14% increase). A number of demographic and clinical factors were significantly associated with cannabis use, including interactions between schizophrenia and gender (area under the curve = 0.88). Conclusions: As medical cannabis policies in Canada have evolved, cannabis use reported prior to first admission to inpatient psychiatry has increased. The findings of this study establish a baseline for evaluating the impact of changes in cannabis-related policies in Ontario on cannabis use prior to admission to inpatient psychiatry