Reducing Postoperative Opioids After Minimally Invasive Hysterectomy with Enhanced Recovery

I Introduction: We evaluated the efficacy of various strategies utilized for the control of postoperative pain after minimally invasive hysterectomy. The primary enhanced recovery after surgery (ERAS) protocol of interest utilized premedication (acetaminophen, celecoxib and pregabalin), then intraoperative subcutaneous liposomal bupivacaine followed by scheduled oral acetaminophen and ibuprofen postoperatively. Patients also had tramadol and oxycodone as needed for moderate or severe breakthrough pain, respectively. Materials and Methods: We conducted a retrospective cohort study that included all patients who underwent minimally invasive hysterectomy (total laparoscopic hysterectomy and laparoscopic-assisted vaginal hysterectomy) for both benign and oncologic indications over a 2-year period. We then compared six protocols, with 3 being ERAS protocols and 3 as traditional pain control methods. The control group was comprised of the traditional pain control group without intraoperative placement of local analgesia. Patient medical records were evaluated for demographics, surgical characteristics, opioid type and dose, pain scores, length of stay and complications. Opioids were converted to oral morphine dose equivalents. Results: 954 patients were included within the 6 protocols. Median opioid usage was the lowest in the ERAS group with premedication and highest in the control group (22.5mg versus 55.0mg, p Discussion: ERAS protocol with premedication was associated with significant reductions in postoperative opioid use and median pain scores when compared to traditional methods

Latent stem and progenitor cells in the hippocampus are activated by neural excitation

The regulated production of neurons in the hippocampus throughout life underpins important brain functions such as learning and memory. Surprisingly, however, studies have so far failed to identify a resident hippocampal stem cell capable of providing the renewable source of these neurons. Here, we report that depolarizing levels of KCl produce a threefold increase in the number of neurospheres generated from the adult mouse hippocampus. Most interestingly, however, depolarizing levels of KCl led to the emergence of a small subpopulation of precursors (approximately eight per hippocampus) with the capacity to generate very large neurospheres (>250 µm in diameter). Many of these contained cells that displayed the cardinal properties of stem cells: multipotentiality and self-renewal. In contrast, the same conditions led to the opposite effect in the other main neurogenic region of the brain, the subventricular zone, in which neurosphere numbers decreased by ~40% in response to depolarizing levels of KCl. Most importantly, we also show that the latent hippocampal progenitor population can be activated in vivo in response to prolonged neural activity found in status epilepticus. This work provides the first direct evidence of a latent precursor and stem cell population in the adult hippocampus, which is able to be activated by neural activity. Because the latent population is also demonstrated to reside in the aged animal, defining the precise mechanisms that underlie its activation may provide a means to combat the cognitive deficits associated with a decline in neurogenesis

Aerococcus urinae isolated from women with lower urinary tract symptoms: In vitro aggregation and genome analysis

Aerococcus urinae is increasingly recognized as a potentially significant urinary tract bacterium. A. urinae has been isolated from urine collected from both males and females with a wide range of clinical conditions, including urinary tract infection (UTI), urgency urinary incontinence (UUI), and overactive bladder (OAB). A. urinae is of particular clinical concern because it is highly resistant to many antibiotics and, when undiagnosed, can cause invasive and life-threatening bacteremia, sepsis, or soft tissue infections. Previous genomic characterization studies have examined A. urinae strains isolated from patients experiencing UTI episodes. Here, we analyzed the genomes of A. urinae strains isolated as part of the urinary microbiome from patients with UUI or OAB. Furthermore, we report that certain A. urinae strains exhibit aggregative in vitro phenotypes, including flocking, which can be modified by various growth medium conditions. Finally, we performed in-depth genomic comparisons to identify pathways that distinguish flocking and nonflocking strains. IMPORTANCE Aerococcus urinae is a urinary bacterium of emerging clinical interest. Here, we explored the ability of 24 strains of A. urinae isolated from women with lower urinary tract symptoms to display aggregation phenotypes in vitro. We sequenced and analyzed the genomes of these A. urinae strains. We performed functional genomic analyses to determine whether the in vitro hyperflocking aggregation phenotype displayed by certain A. urinae strains was related to the presence or absence of certain pathways. Our findings demonstrate that A. urinae strains have different propensities to display aggregative properties in vitro and suggest a potential association between phylogeny and flocking

A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals

Urinary tract infection is among the most common infections worldwide, typically studied in animals and cell lines with limited uropathogenic strains. Here, we assessed diverse bacterial species in a human urothelial microtissue model exhibiting full stratification, differentiation, innate epithelial responses, and urine tolerance. Several uropathogens invaded intracellularly, but also commensal Escherichia coli, suggesting that invasion is a shared survival strategy, not solely a virulence hallmark. The E. coli adhesin FimH was required for intracellular bacterial community formation, but not for invasion. Other shared lifestyles included filamentation (Gram-negatives), chaining (Gram-positives), and hijacking of exfoliating cells, while biofilm-like aggregates were formed mainly with Pseudomonas and Proteus. Urothelial cells expelled invasive bacteria in Rab-/LC3-decorated structures, while highly cytotoxic/invasive uropathogens, but not commensals, disrupted host barrier function and strongly induced exfoliation and cytokine production. Overall, this work highlights diverse species-/strain-specific infection strategies and corresponding host responses in a human urothelial microenvironment, providing insights at the microtissue, cell, and molecular level

Agricultural development addresses food loss and waste while reducing greenhouse gas emissions

Food loss and waste (FLW) reduce food available for consumption and increase the environmental burden of production. Reducing FLW increases agricultural and value-chain productivity and may reduce greenhouse gas emissions associated with feeding the global population. Although studies of interventions that reduce FLW exist, almost no research systematically investigates FLW interventions across multiple value chains or countries, most likely due to challenges in collecting and synthesizing data and estimates, let alone estimating greenhouse gas emissions. Our research team investigated changes in FLW in projects supported by the United States Agency for International Development\u27s (USAID) global hunger and food security initiative, Feed the Future. This was a unique opportunity to conduct ex-ante estimates of the impacts of FLW interventions across 20 value chains in 12 countries, based on project documents and interviews with USAID and project staff. This paper describes specific interventions in each value chain and country context, providing insight to interventions that decrease FLW at multiple points along food value chains, from upstream producer-dominated stages to downstream consumer-dominated stages. Amongst the sub-sectors studied, FLW interventions directed at extensive dairy systems could decrease FLW by 4–10%, providing meaningful greenhouse gas mitigation, since these systems are both emission-intensive and experience high FLW. More modest emissions reductions were found for other key agricultural products, including maize, rice, vegetables, fruits and market goods

Voluntary Exercise Reduces Alzheimer’s-like Pathology After Inflammation in Mice

Current global statistics estimate that 44.4 million people are afflicted with dementia, and that 50%-75% of these patients suffer from Alzheimer’s disease (AD; Prince et al. 2013). AD, a progressive disorder categorized by neuronal and behavioral deterioration, is the 6th leading cause of death in America (Alz facts and figure 2012). One hallmark pathology of AD is the presence of amyloid-beta (Aβ) in the brain, which can limit cell-to-cell communication, leading to cognitive deficits, and neuronal cell death. Although the exact origins of this disease still remain unknown, one possible catalyst of AD pathology is inflammation. Our lab has previously shown that 7 consecutive peripheral injections of a bacterial mimetic led to systemic inflammation, increased levels of Ab in the brain, and cognitive dysfunction (Kahn et al., 2012; Weintraub et al., 2013). Currently there are very few effective treatments that diminish AD symptomology. One documented way to decrease inflammation without the use of pharmaceuticals is through regular physical exercise (Cho et al., 2003; Cotman & Berchtold, 2002; Cotman et al., 2007). The present study tested the hypothesis that voluntary exercise would decrease the level of brain Ab following inflammation. Interestingly, we found that two weeks of voluntary wheel running after inflammation led to a reduction of Ab when compared to sedentary recovery. These results indicate that exercise may be an effective modality to reduce AD-like pathology, and that these effects appear to be facilitated by higher versus lower levels of exercise, as measured by total distance run

Demonstrating high-precision photometry with a CubeSat: ASTERIA observations of 55 Cancri e

ASTERIA (Arcsecond Space Telescope Enabling Research In Astrophysics) is a 6U CubeSat space telescope (10 cm x 20 cm x 30 cm, 10 kg). ASTERIA's primary mission objective was demonstrating two key technologies for reducing systematic noise in photometric observations: high-precision pointing control and high-stabilty thermal control. ASTERIA demonstrated 0.5 arcsecond RMS pointing stability and $\pm$10 milliKelvin thermal control of its camera payload during its primary mission, a significant improvement in pointing and thermal performance compared to other spacecraft in ASTERIA's size and mass class. ASTERIA launched in August 2017 and deployed from the International Space Station (ISS) November 2017. During the prime mission (November 2017 -- February 2018) and the first extended mission that followed (March 2018 - May 2018), ASTERIA conducted opportunistic science observations which included collection of photometric data on 55 Cancri, a nearby exoplanetary system with a super-Earth transiting planet. The 55 Cancri data were reduced using a custom pipeline to correct CMOS detector column-dependent gain variations. A Markov Chain Monte Carlo (MCMC) approach was used to simultaneously detrend the photometry using a simple baseline model and fit a transit model. ASTERIA made a marginal detection of the known transiting exoplanet 55 Cancri e ($\sim2$~\Rearth), measuring a transit depth of $374\pm170$ ppm. This is the first detection of an exoplanet transit by a CubeSat. The successful detection of super-Earth 55 Cancri e demonstrates that small, inexpensive spacecraft can deliver high-precision photometric measurements.Comment: 23 pages, 9 figures. Accepted in A

Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension

To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. Junctional stability is dependent on actomyosin contractility within the actin ring. Here we describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability. Loss of Neogenin perturbs AJs and attenuates junctional tension. Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory complex (WRC) and Arp2/3. A direct interaction between the Neogenin WIRS domain and the WRC is crucial for the spatially restricted recruitment of the WRC to the junction. Thus, we provide the first example of a functional WIRS-WRC interaction in epithelia. We further show that Neogenin regulates cadherin recycling at the AJ. In summary, we identify Neogenin as a pivotal component of the AJ, where it influences both cadherin dynamics and junctional tension

Annotated Bibliography for the MATADOR Project

The MATADOR project is focused on developing methods to infer the operational mode of facilities that have the potential to be used in weapons development programs. Our central hypothesis is that by persistent, non-intrusive monitoring of such facilities, differences between various use scenarios can be reliably discovered. The impact of success in this area is that new tools and techniques for monitoring and treaty verification would make it easier to reliably discover and document weapons development activities. This document captures the literature that will serve as a basis to approach this task. The relevant literature is divided into topical areas that relate to the various aspects of expected MATADOR project development. We have found that very little work that is directly applicable for our purposes has been published, which has motivated the development of novel methods under the project. Therefore, the manuscripts referenced in this document were selected based on their potential use as foundational blocks for the methods we anticipate developing, or so that we can understand the limitations of existing methods

Combined mTOR and MEK inhibition is an effective therapy in a novel mouse model for angiosarcoma

Angiosarcoma is an aggressive malignancy of vascular origin that occurs de novo or in the context of previous cancer therapy. Despite multi-modal aggressive treatment including surgical resection, chemotherapy, and radiation, five-year overall survival remains poor at 35%. Due to its rarity, little is known about its molecular pathology and clinical trials have been extremely difficult to conduct. Development of animal models for rare diseases like angiosarcoma is critical to improve our understanding of tumorigenesis and to test novel treatment regimens. A genetically engineered mouse model for angiosarcoma was generated by conditional deletion of Trp53, Pten, and Ptpn12 in endothelial cells. Tumors arising from these mice recapitulate the histology and molecular pathology of the human disease including hyperactivation of the PI3K/mTOR and MAPK signaling pathways. Treatment of tumor-bearing mice with mTOR or MEK inhibitors effectively inactivated signaling and resulted in reduced proliferation and elevated apoptosis leading to tumor regression. The effect of treatment on tumor growth was transient and proliferation was restored after a period of dormancy. However, combined inhibition of mTOR and MEK resulted in profound tumor regression which was sustained for the duration of treatment. These results suggest that angiosarcoma may be effectively treated by this drug combination