Objectives The aim of the study was to describe emtricitabine pharmacokinetics during pregnancy and postpartum. Methods The International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT), formerly Pediatric AIDS Clinical Trials Group (PACTG), study P1026s is a prospective pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including a cohort taking emtricitabine 200 mg once daily. Intensive steady-state 24-hour emtricitabine pharmacokinetic profiles were performed during the third trimester and 6–12 weeks postpartum, and on maternal and umbilical cord blood samples collected at delivery. Emtricitabine was measured by liquid chromatography–mass spectrometry with a quantification limit of 0.0118 mg/L. The target emtricitabine area under the concentration versus time curve, from time 0 to 24 hours post dose (AUC0-24), was ≥7 mg h/L (≤30% reduction from the typical AUC of 10 mg h/L in nonpregnant historical controls). Third-trimester and postpartum pharmacokinetics were compared within subjects. Results Twenty-six women had pharmacokinetics assessed during the third trimester (median 35 weeks of gestation) and 22 postpartum (median 8 weeks postpartum). Mean [90% confidence interval (CI)] emtricitabine pharmacokinetic parameters during the third trimester vs. postpartum were, respectively: AUC: 8.0 (7.1–8.9) vs. 9.7 (8.6–10.9) mg h/L (P = 0.072); apparent clearance (CL/F): 25.0 (22.6–28.3) vs. 20.6 (18.4–23.2) L/h (P = 0.025); 24 hour post dose concentration (C24): 0.058 (0.037–0.063) vs. 0.085 (0.070–0.010) mg/L (P = 0.006). The mean cord:maternal ratio was 1.2 (90% CI 1.0–1.5). The viral load was <400 HIV-1 RNA copies/mL in 24 of 26 women in the third trimester, in 24 of 26 at delivery, and in 15 of 19 postpartum. Within-subject comparisons demonstrated significantly higher CL/F and significantly lower C24 during pregnancy; however, the C24 was well above the inhibitory concentration 50%, or drug concentration that suppresses viral replication by half (IC50) in all subjects. Conclusions While we found higher emtricitabine CL/F and lower C24 and AUC during pregnancy compared with postpartum, these changes were not sufficiently large to warrant dose adjustment during pregnancy. Umbilical cord blood concentrations were similar to maternal concentrations.

Breast cancer (BC) is a leading cause of cancer-related death in women. Adjuvant systemic chemotherapies are effective in reducing risks of recurrence and have contributed to reduced BC mortality. Although targeted adjuvant treatments determined by biomarkers for endocrine and HER2-directed therapies are largely successful, predicting clinical benefit from chemotherapy is more challenging. Drug resistance is a major reason for treatment failures. Efforts are ongoing to find biomarkers to select patients most likely to benefit from chemotherapy. Importantly, cell surface biomarkers CD44+/CD24− are linked to drug resistance in some reports, yet underlying mechanisms are largely unknown. This study focused on the potential role of CD24 expression in resistance to either docetaxel or doxorubicin in part by the use of triple-negative BC (TNBC) tissue microarrays. In vitro assays were also done to assess changes in CD24 expression and differential drug susceptibility after chemotherapy. Further, mouse tumor xenograft studies were done to confirm in vitro findings. Overall, the results show that patients with CD24-positive TNBC had significantly worse overall survival and disease-free survival after taxane-based treatment. Also, in vitro cell studies show that CD44+/CD24+/high cells are more resistant to docetaxel, while CD44+/CD24−/low cells are resistant to doxorubicin. Both in vitro and in vivo studies show that cells with CD24-knockdown are more sensitive to docetaxel, while CD24-overexpressing cells are more sensitive to doxorubicin. Further, mechanistic studies indicate that Bcl-2 and TGF-βR1 signaling via ATM-NDRG2 pathways regulate CD24. Hence, CD24 may be a biomarker to select chemotherapeutics and a target to overcome TNBC drug resistance.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

Introduction: There is little consensus of quality measurements for restorative proctocolectomy with ileal pouch-anal anastomosis(RPC-IPAA) performed for ulcerative colitis(UC). The National Surgical Quality Improvement Program(NSQIP) cannot accurately classify RPC-IPAA staged approaches. We formed an IBD-surgery registry that added IBD-specific variables to NSQIP to study these staged approaches in greater detail. Methods: We queried our validated database of IBD surgeries across 11 sites in the US from March 2017 to March 2019, containing general NSQIP and IBD-specific perioperative variables. We classified cases into delayed versus immediate pouch construction and looked for independent predictors of pouch delay and postoperative Clavien-Dindo complication severity. Results: 430 patients received index surgery or completed pouches. Among completed pouches, 46(28%) and 118(72%) were immediate and delayed pouches, respectively.

Background Watch and wait (WW) protocols have gained increasing popularity for patients diagnosed with locally advanced rectal cancer and presumed complete clinical response after neoadjuvant chemoradiation. While studies have demonstrated comparable survival and recurrence rates between WW and radical surgery, the decision to undergo surgery has significant effects on patient quality of life. We sought to conduct a cost-effectiveness analysis comparing WW with abdominoperineal resection (APR) and low anterior resection (LAR) among patients with stage II/III rectal cancer. Methods In this comparative-effectiveness study, we built Markov microsimulation models to simulate disease progression, death, costs, and quality-adjusted life-years (QALYs) for WW or APR/LAR. We assessed cost effectiveness using the incremental cost-effectiveness ratio (ICER), with ICERs under $100,000/QALY considered cost effective. Probabilities of disease progression, death, and health utilities were extracted from published, peer-reviewed literature. We assessed costs from the payer perspective. Results WW dominated both LAR and APR at a willingness to pay (WTP) threshold of $100,000. Our model was most sensitive to rates of distant recurrence and regrowth after WW. Probabilistic sensitivity analysis demonstrated that WW was the dominant strategy over both APR and LAR over 100% of iterations across a range of WTP thresholds from $0–250,000. Conclusions Our study suggests WW could reduce overall costs and increase effectiveness compared with either LAR or APR. Additional clinical research is needed to confirm the clinical efficacy and cost effectiveness of WW compared with surgery in rectal cancer.

Purpose: Restorative proctocolectomy(RPC) is performed for patients with refractory ulcerative colitis(UC). This operation is performed in 2 or 3-stages and involves forming a diverting loop ileostomy thought to protect patients from complications related to anastomotic leak. However, some advocate for a modified 2-stage approach, consisting of subtotal colectomy followed by completion proctectomy and ileal pouch anal anastomosis without diverting ileostomy. We present a systematic review and meta-analysis comparing postoperative complication rates between modified 2-stage and traditional RPC with ileal pouch anal anastomosis.Methods: Records were sourced from PubMed/Embase databases. Studies comparing postoperative complications following RPC for ulcerative colitis(UC) were selected according to PRISMA guidelines comparing modified 2-stage(exposure), classic 2-stage, and 3-stage approaches(comparators). The primary outcome measure was safety as measured by postoperative complication rates. We employed random-effects meta-analysis. Results:We included ten observational studies including 1727 patients(38% modified 2-stage). Among pediatric patients, modified 2-stage approaches had higher rates of anastomotic leak than 3-stage approaches(p=0.03). Among adult cohorts with lower preoperative biologic use rates, modified 2-stage approaches had lower leak rates than classic 2-stage approaches(p<0.001). Conclusions:The modified 2-stage approach may be safe for adult patients who otherwise require a 3-stage approach while reducing costs and length of stay. Pediatric patients may benefit

It is well known that a tangential force larger than the maximum static friction force is required to initiate the sliding motion between two objects, which is governed by a material constant called the coefficient of static friction. Therefore, knowing the coefficient of static friction is of great importance for robot grippers which wish to maintain a stable and precise grip on an object during various manipulation tasks. Importantly, it is most useful if grippers can estimate the coefficient of static friction without having to explicitly explore the object first, such as lifting the object and reducing the grip force until it slips. A novel eight-legged sensor, based on simplified theoretical principles of friction is presented here to estimate the coefficient of static friction between a planar surface and the prototype sensor. Each of the sensor's eight legs are straight and rigid, and oriented at a specified angle with respect to the vertical, allowing it to estimate one of five ranges (5 = 8/2 + 1) that the coefficient of static friction can occupy. The coefficient of friction can be estimated by determining whether the legs have slipped or not when pressed against a surface. The coefficients of static friction between the sensor and five different materials were estimated and compared to a measurement from traditional methods. A least-squares linear fit of the sensor estimated coefficient showed good correlation with the reference coefficient with a gradient close to one and an r(2) value greater than 0.9.

VA is superior to nonoperative care in reducing lower back pain for osteoporotic VCFs with correlating signs and symptoms. VA had no benefit over nonoperative care for chronic VCFs that lacked clinical correlation. Lower back pain has many etiologies and patients should be clinically assessed before recommending VA.