Impacts of hypophosphatemia on gene expression needed for bone fracture repair

Bone fractures are one of the most common injuries in the United States, encompassing 6.2 million incidences, and costing the healthcare system roughly $20 billion annually. The majority of this cost falls upon a unique type of fracture known as a non-union fracture, defined by incomplete healing after 9 months. The economic burden in combination with the frequency by which these incidences occur offer a unique opportunity for research and improvement in the healthcare field. Previous research on the fracture repair process showed that dietary deficiency led to delayed healing producing a rachitic-like effect on the endochondral bone formation process that occurs during fracture healing. This research will build off the understanding of hypophosphatemia on bone fracture repair utilizing a unique temporal clustering approach to assess changes in the transcriptomic expression within callus tissues of control fed and dietary phosphate restricted animals. Using a temporal cluster modeling technique developed by our group (Lu et al. 2019), twelve clusters were generated for the gene expression data extracted from the callus tissues of B6 strain mice at time points 3, 5, 7, 10, 14, 18-, 21-, 28-, and 35-days post fracture, in, control and phosphate restricted dietary groups. Groupings of clusters were used to establish the temporal expression patterns over the time course of healing and identify the movement of genes that changed their temporal expression patterns between the control and phosphate restricted diets. Biological process categories were established for each cluster, grouping using both Ingenuity Pathway Analysis (IPA) and the NIH DAVID Bioinformatics Database ontology assessment programs. Genes based on their association with four key tissue developmental processes in fracture repair, skeletogenesis, myogenesis, vasculogenesis, and neurogenesis were analyzed. The analysis showed shifts to later peak expression times for all four categories. Further analysis illuminated three specific regulatory pathways that were significantly impacted by hypophosphatemia, Hippo and WNT signaling pathways and the circadian rhythm pathway while oxidative phosphorylation was both shifted and showed reduced expression. The shifts in expression time and level of these pathways demonstrate their importance to bone fracture repair and their impacts on mesenchymal stem cell differentiation. From the data analysis it is clear that limiting dietary phosphate results in impaired mesenchymal stem cell differentiation caused by delayed Hippo and WNT signaling. Further it is evident that the processes of skeletogenesis, myogenesis, vasculogenesis, and neurogenesis are heavily interconnected, often showing overlapping genes through all four processes. Based on these shifts and impairments in specific signaling we identified novel mechanisms by which hypophosphatemia can impair fracture callus growth and development and delay healing

No Wedding Bells For Her

https://digitalcommons.library.umaine.edu/mmb-vp/4549/thumbnail.jp

Sing Me A Song Of The South

https://digitalcommons.library.umaine.edu/mmb-vp/6493/thumbnail.jp

Nutritional Evaluation of Food Bank Services in Chittenden and Addison Counties, Vermont

Background: Feeding Chittenden and Addison Food Shelf are programs that alleviate hunger in Vermont utilizing the Food Access Network. This Network allows customers to select food and have it delivered to a location of their choice, with an aim of providing healthier foods while reducing barriers and stigma. Methods: Using nutritional standards adapted from a BMC Public Health study [1], food items delivered from March- May 2023 were scored based on category, amount of saturated fat, sodium, and added sugar. Scores included ‘1,’ recommended often, ‘2,’ recommended sometimes, and ‘3,’ recommended rarely. Analysis was conducted on total offerings, total orders, and order pickup/drop-off locations in the two counties. Results: The average score for the food offered in Chittenden v. Addison County was 1.69 v. 1.60 with Chittenden being 45.9% foods scored ‘1,’ 39.3% ‘2,’ and 14.8% ‘3,’ and Addison being 51.7% ‘1,’ 36.3% ‘2,’ and 12.1% ‘3.’Although Addison offered more food options scored as ‘1’ it demonstrated a higher average order score (1.83) compared to Chittenden (1.62). This trend continued when analyzing pick-up/drop-off locations as 71% of Addison sites versus 7.7% of Chittenden sites had foods scored ‘2’ as their highest percentage of items ordered. Conclusion: While at baseline one may consider a direct correlation between the food choices offered and the ordering habits of an individual, it is evident from this data that there are factors beyond ordering options that are impacting ordering habits. Previous research suggests an unexplained difference between rural and urban counties when it comes to dietary intake (Euler 2019). When considering the limitations of previous studies and the robust data available through this study in combination with Rural Urban Commuting Area (RUCA) Code, future research will be able to further explore the differences in nutritional habits by county, allowing more targeted interventions to address these differences. Future Directions: Going forward, there are many directions future research could pursue with CVOEO. Our initial research was a descriptive study of Chittenden and Addison counties stocked and outgoing foods. A metric we used in our data analysis was the selected drop-off locations. Additional metrics that could be used to analyze the data are the age of the registrant, the home zip code, and the referral source. Each of these metrics could allow for more information to be gathered about specific populations that utilize the Food Access Network. Additionally, an interventional study could be done. At the current moment, Chittenden, and Addison County list their produce and meats differently. Addison County lists the specific produce and meat, while Chittenden County offers “assorted” categories of each. Standardizing the listing and then studying potential changes in ordering trends is a potential direction for future stud

Sing Me a Song of the South / music by James W. Casey; words by George A. Norton

Cover: description reads pathetic descriptive ballad; Publisher: M. Witmark and Sons (New York)https://egrove.olemiss.edu/sharris_a/1053/thumbnail.jp

Antenatal Betamethasone for Women at Risk for Late Preterm Delivery

Infants born at 34 to 36 weeks’ gestation (late preterm) have greater risks of adverse respiratory and other outcomes, than those born at 37 weeks gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases risks of neonatal morbidities

Stability in Cosmology, from Einstein to Inflation

I investigate the role of stability in cosmology through two episodes from the recent history of cosmology: (1) Einstein’s static universe and Eddington’s demonstration of its instability, and (2) the flatness problem of the hot big bang model and its claimed solution by inflationary theory. These episodes illustrate differing reactions to instability in cosmological models, both positive ones and negative ones. To provide some context to these reactions, I also situate them in relation to perspectives on stability from dynamical systems theory and its epistemology. This reveals, for example, an insistence on stability as an extreme position in relation to the spectrum of physical systems which exhibit degrees of stability and fragility, one which has a pragmatic rationale, but not any deeper one

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, \u3c160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks\u27 gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.)

Association between Features of Spontaneous Late Preterm Labor and Late Preterm Birth

Objective This study aimed to evaluate the association between clinical and examination features at admission and late preterm birth. Study Design The present study is a secondary analysis of a randomized trial of singleton pregnancies at 34 0/7 to 36 5/7 weeks' gestation. We included women in spontaneous preterm labor with intact membranes and compared them by gestational age at delivery (preterm vs. term). We calculated a statistical cut-point optimizing the sensitivity and specificity of initial cervical dilation and effacement at predicting preterm birth and used multivariable regression to identify factors associated with late preterm delivery. Results A total of 431 out of 732 (59%) women delivered preterm. Cervical dilation ≥ 4 cm was 60% sensitive and 68% specific for late preterm birth. Cervical effacement ≥ 75% was 59% sensitive and 65% specific for late preterm birth. Earlier gestational age at randomization, nulliparity, and fetal malpresentation were associated with late preterm birth. The final regression model including clinical and examination features significantly improved late preterm birth prediction (81% sensitivity, 48% specificity, area under the curve = 0.72, 95% confidence interval [CI]: 0.68-0.75, and p -value < 0.01). Conclusion Four in 10 women in late-preterm labor subsequently delivered at term. Combination of examination and clinical features (including parity and gestational age) improved late-preterm birth prediction