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Characterizing the Role of the E. Coli Cytochrome Oxidase AppBCX During Intestinal Inflammation
No full textDuring non-infectious colitis, oral antibiotic treatment, and enteric infection, changes in colonocyte metabolism allow for increased oxygen availability in the gut lumen, supporting the growth of facultative anaerobic bacteria primarily from the family Enterobacteriaceae. Additionally, recruitment of inflammatory cells, especially neutrophils, has also been shown to influence local oxygen levels. The oxidative burst mounted by neutrophils consumes oxygen, which in turn creates a hyper-hypoxic microenvironment. These two seemingly contradictory findings remain to be reconciled. The findings described here delineate an additional mechanism that helps explain these seemingly contradictory observations on oxygen availability and bacterial respiratory processes during non-infectious colitis. The picture emerging from our work is that reactive oxygen species (ROS) generated by the NADPH oxidase 1 (NOX1) at the epithelial interface serve as a local source of oxygen. Specifically, H2O2 deriving from epithelial NOX1, is detoxified via bacterial catalases to molecular oxygen. Facultative anaerobic bacteria can then respire this pool of oxygen. In this work, we have used commensal strains of E. coli as representative members of Enterobacteriaceae, a family of facultative anaerobic bacteria that is observed to outgrow during episodes of inflammation. In particular, we have studied the physiological function of the cytochrome bd oxidase, AppBCX. Using both chemical and genetic models of non-infectious colitis we have shown that it allows E. coli to utilize low levels of oxygen early in inflammation. Additionally, we have characterized the regulation of this enzyme in vivo highlighting the delicate balance between growth and survival during oxidative and nitrosative stress
How Will I Find You
No full textThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.I am one of five children in my family. There was a big brother who passed away at birth who I never met. I have often wondered who he would have been and what my family and mostly myself missed out on. We'll never know. Or perhaps one day I will
Hold On
No full textThe author submitted this entry in the 10-Word Story category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.This work received a Second Place Award in the "10-Word Story" category from all literary works submitted in the 2023 On My Own Time show.The inspiration were the human connections and innovations that care providers made in an uncertain world those facing death in isolation when family could not be with them. This is written for those who made sure to hold on to the hands as the ravished body surrendered to infection. Hold on to the love, and to our human spirits between us even during death
Ethics Grand Rounds Calendar: 2023/2024
No full textThe published schedule of Ethics Grand Rounds events for fiscal year 2024 (i.e., September 2023 - August 2024).This document lists the schedule of Ethics Grand Rounds events for September 2023 through May 2024
Alport syndrome: updates in genetics, pathogenesis and therapies
Get PDFDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin
Aspartate Is Limiting for Hematopoietic Stem Cell Function in vivo
No full textA key function of the electron transport chain is to promote aspartate synthesis, which is required for cancer cell proliferation. However, it is unclear whether aspartate is also limiting in normal stem cells, which divide intermittently. We found that hematopoietic stem cells (HSCs) do not take up exogenous aspartate. To test if aspartate limits HSC function, we over-expressed the glutamate/aspartate transporter, Glast, or deleted glutamic-oxaloacetic transaminase 1 (Got1). Each increased aspartate levels in hematopoietic stem/progenitor cells, increasing the function of HSCs but not colony-forming progenitors. Conversely, deletion of glutamic-oxaloacetic transaminase 2 (Got2) reduced aspartate levels and HSC function but not colony-forming progenitors. Isotope tracing showed aspartate was used to synthesize asparagine and purines. Both contributed to increased HSC function as deletion of asparagine synthetase (Asns) or treatment with 6-mercaptopurine attenuated the increased function of GLAST over-expressing HSCs. Stem cell function is thus limited by aspartate in some contexts
Determination of the Optimal Targeted Prostate Biopsy Strategy
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.BACKGROUND: Prostate cancer is one of the leading causes of cancer-related mortality in men and is treated in different ways based on the aggressiveness of the disease. The traditional method of diagnosis has been the systematic biopsy, which frequently underestimates or completely misses the disease. Recently, targeted prostate biopsies using pre-biopsy multiparametric MRI (mpMRI) have increased the detection of clinically significant disease. Of these methods, the two most sophisticated types are the MRI-TRUS fusion biopsy and the direct in-bore biopsy. Data comparing the diagnostic accuracy of these approaches and optimization of the biopsy procedure are lacking.
OBJECTIVE: To compare the diagnostic accuracy of in-bore biopsy and MRI-TRUS fusion biopsy at accurately determining the index lesion grade group compared to radical prostatectomy (Aim 1), and to establish the optimal number of cores taken during in-bore biopsies to maximize detection of clinically significant disease while minimizing duration of the biopsy (Aim 2).
METHODS: In Aim 1, patients that had at least one prostate lesion with abnormal mpMRI (at least one PI-RADS score 3 lesion) followed by targeted biopsy between April 2017 and January 2019 were included. The decision of what biopsy method to use for each patient was made by the ordering provider. The index lesion was defined as the largest lesion that exhibited the highest grade group (GG) and/or stage. The reference standard was the highest GG obtained from the radical prostatectomy specimen. In Aim 2, patients with abnormal mpMRI followed by in-bore biopsy between May 2017 and December 2019 were included. The endpoints of the study were the detection rate of clinically significant disease (defined as a GG of at least 2) and the GG upgrade (defined as the increase in the cumulative maximum GG with each additional core).
RESULTS: In Aim 1, there was a statistically significant difference in the number of GG upgrades between the two biopsy types, with the in-bore biopsy having fewer (14%) upgrades than the fusion biopsy (30%; p=0.012). The mean net GG change was also significantly lower in the in-bore cohort (-0.11) compared to the fusion cohort (+0.16; p=0.0085). The GG concordance of the in-bore cohort (61%) was higher than the fusion cohort (53%) when compared to radical prostatectomy. In Aim 2, clinically significant cancers were detected by the first biopsy core in 78% of cases, the second core in 13% of cases, and the third core in 8.1% of cases. Only two lesions had the fourth core find csPCa. GG upgrade from insignificant to significant disease was also higher in the second and third cores (3%) compared to the fourth and fifth cores. The fourth and fifth cores only detected 0.3% of clinically significant tumors and resulted in only 1.2% of GG upgrades.
CONCLUSION: Direct in-bore MRI-guided biopsy has greater diagnostic accuracy and a lower incidence of GG upgrades compared to MRI-TRUS fusion biopsy. Three cores per lesion was determined to offer the optimal balance between increasing the detection of clinically significant cancers and minimizing biopsy duration. Future work will center around cost-effective analyses and the impact on long-term patient outcomes
Emith
No full textThe author submitted this entry in the Fictional Short Story category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.I guess the story is merely a reflection of my own life experiences and personal encounters with these technologies. It intertwines my own imperfections and limitations, presenting a relatable almost protagonist craft, driven by an authentic yearning to assist others and contribute to the improvement of our world. For me, the tale is the canvas in which I can explore the possibilities that lie beyond reality's boundaries
Cervical Cancer Treatment Pathway in Botswana
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.BACKGROUND: The incidence and mortality of cervical cancer in Botswana are among the highest in the world. Despite availability of chemoradiation and government funding for cancer treatment, many patients referred for chemoradiation in Botswana do not receive treatment.
OBJECTIVES: This study sought to determine the proportion of cervical cancer patients referred for chemoradiation who do not receive cancer treatment and identify factors associated with receipt or non-receipt of treatment. Time between key steps in the care cascade was quantified to identify points that contribute to delays in care. This study also examined the impact of Princess Marina Hospital's multidisciplinary gynecologic oncology (PMH MDT) clinic on treatment receipt.
METHODS: 230 patients with biopsy-proven cervical cancer were enrolled from January 2015 to July 2018 at Princess Marina Hospital in Gaborone, Botswana and followed until November 2019. Patient demographics, clinical characteristics, treatment characteristics, and time between steps in the care cascade were compared between treated and untreated patients using Wilcoxon rank sum tests, chi-squared tests, student's t tests, and univariate binomial logistic regression.
RESULTS: 43 (18.7%) patients did not receive cancer treatment. Higher FIGO stage at initial presentation (OR: 0.50, 95% CI: 0.31-0.83, p 0.05).
CONCLUSION: The MDT model is an evidence-based strategy to improve care coordination and reduce treatment disparities, thus improving outcomes for cancer patients. While there are still gaps in Botswana's cervical cancer care cascade, the PMH MDT clinic has led to significant improvements in cancer care among this population. The PMH MDT clinic provides strong evidence that MDT clinics can and should be established in under-resourced settings
Ice-POP: Ice Application for Post-Operative Pain: A Randomized Controlled Trial
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.BACKGROUND: The Opioid Crisis is directly linked to over-prescription of opioids by physicians. Non-opioid and non-pharmacologic forms of post-operative pain management need to be explored. Cryotherapy, accomplished with the use of ice, is a non-pharmacologic form of pain relief. There is limited data regarding cryotherapy and its application in abdominal surgery.
OBJECTIVE: To investigate the effectiveness of cryotherapy as an additional form of pain control in women undergoing total laparoscopic hysterectomy (TLH) for benign gynecologic conditions through a randomized trial.
METHODS: 52 patients were randomized evenly to receive standardized post-operative pain management with or without cryotherapy (abdominal ice packs applied directly following surgery). VAS pain scores and narcotic usage were collected at the patient's pre-op appointment, before surgery, at discharge, during a 1-day post-op phone interview, and at a 2-week post-op appointment. Questions about the patient's perception of pain were asked during the postoperative day 1 phone call. Quality of recovery scales were collected at enrollment and the 2-week post-op appointment. Demographic data, VAS pain scores, and narcotic usage were analyzed for significance via the student's t-test.
RESULTS: There was no statistically significant difference (p < 0.05) between the patient group receiving ice and no ice based on demographics, VAS pain score, narcotic usage, quality of recovery, and perception of pain control. However, for patients using ice, VAS pain scores were lower on postoperative day 1 and narcotic usage was lower in the post-anesthesia care unit (PACU). Patient perception of ice was largely positive with 87% of patients reporting they would use ice again while 83% would recommend ice to family/friends. Of note, less than half (38%) of opioids prescribed were used within 2 weeks post-op.
CONCLUSION: Based on the minimal risks of ice, low cost, and perceived benefit by patients including the opportunity for patient autonomy, we would recommend using ice immediately following surgery. Ice is a reasonable alternative to decrease the number of opiates prescribed