UC Davis

The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.

Wildfires are impacting communities globally, with California wildfires often breaking records of size and destructiveness. Knowing how communities are affected by these wildfires is vital to understanding recovery. We sought to identify impacted communities' post-wildfire needs and characterize how those needs change over time. The WHAT-Now study deployed a survey that was made publicly available for communities affected by the October 2017 Northern California wildfires or the accompanying smoke at beginning approximately four months post-fire with the vast majority completed by nine months post-fire. Among other questions, the survey asked an adult household member to report on their households' greatest need both one-week post-fire and at the time of survey. A total of 1461 households responded to these questions. Households reported many types of needs, with 154 responses that did not directly name needs but rather described how their households had been affected, which we classified as impacts. Four major themes were identified: physical, health, air, and information, each representing an array of varied specific needs or impacts. Physical needs (e.g. housing, food) were the most common (cited by more than 50% during the fires and about a third at the time of survey). The need for clean air was strong during the fires, but not months later, at the time of survey. In contrast, health needs were reported by a quarter of households during the fires. Needs that were reported at both times were categorized as 'persistent', and there were more persistent mental health needs over time compared to other health themes. Understanding the needs and impacts that arise during wildfires, their diversity and duration, and how they change over time is crucial to identifying types of assistance that are most needed during recovery efforts and when they are needed. Results presented here along with other wildfire needs assessments can be utilized to improve disaster preparedness, including for wildfire recovery.

Substituting Portland cement (PC) with supplementary cementitious materials (SCMs) is a key strategy for reducing greenhouse gas (GHG) emissions. Considering alternative SCMs requires a holistic understanding of changes to material performance, emissions reduction potential, and regional availability. Four rice hull ashes (RHAs) and one rice straw ash (RSA) were evaluated to replace PC in mortars (10% untreated ash and 30% blast furnace slag; 15% untreated ash; or 15% milled ash). The 28-day compressive strengths with 0.59 water-to-binder ratio for fly-RHAs (38.0–49.8 MPa) and RSA (37.7 - 44.1 MPa) did not vary significantly from the PC control (43.2 MPa) based on an ANOVA. Modeling rice biomass generation in six U.S. states shows RSA could triple the supply of rice-biomass ash, but in states with substantial PC demand, i.e., California and Texas, the potential GHG reduction may remain small (∼1–2%). RSA and RHA may hold promise in lowering concrete GHG emissions.

We report disseminated mycosis in a Belgian Malinois caused by Scytalidium philadelphianum. The dog presented for progressive hindlimb weakness after diagnosis of suspected bacterial discospondylitis. Magnetic resonance imaging combined with radiographs revealed multifocal discospondylitis, osteomyelitis, and spondylitis with epidural empyema. Scytalidium philadelphianum was identified on culture and DNA sequencing of urine and fine needle aspirates of affected disc spaces. Aggressive therapy including amphotericin B liposomal complex, micafungin, and azoles were initiated, but the dog was euthanized seven months later due to progressive neurologic disease. This is the first report of disseminated disease by Scytalidium philadelphianum in veterinary medicine.

Degeneration of the thoracoabdominal aorta proximal to a prior fenestrated endovascular aortic repair represents a complex issue with limited options for repair. Previously, modified endografts or open conversion with endograft explant offered the only options for management. Here we describe use of the Gore Thoracoabdominal Multibranch Endoprosthesis for exclusion of an extent III thoracoabdominal aneurysm in the setting of degeneration proximal to a previously placed fenestrated device.

In Spring 2020, colleges across the nation swiftly transitioned their operations—including both classes and student support services—to remote delivery on an emergency basis in response to the crisis posed by the COVID-19 pandemic. While prior research has documented that the transition was associated with decrements in student outcomes, there remains limited understanding of the organizational factors that might have mitigated these negative associations during the pandemic. Drawing on administrative data from the California Community College system, along with a novel survey conducted among distance education leaders, our study reveals that the degree of declines in course completion and course passing rates varied based on pre-COVID online education resources (such as the ratio of distance education personnel to students and the availability of pre-COVID professional development programs in online learning): Colleges with greater pre-COVID online resources experienced more modest declines in student performance. To a lesser extent, we also found that declines in student performance during the onset of the pandemic varied depending on the responses implemented in reaction to the pandemic, such as the extent of technology delivery to students. The implications of our findings extend to the realm of planning for the continuity of operations in potential future crises.

This work evaluates the ability of various lipid-based amphiphilic small molecules (ASMs) to modulate the mechanical and rheological properties of oleogels principally structured by ethyl cellulose (EC). Six ASMs varying in the chemical structure of their polar headgroups were used to produce EC-ASM oleogels. Stearic acid (StAc), monoacylglycerol (MAG), sodium stearoyl lactylate (SSL), and citric acid esters of monoglycerides (CITREM) all provided a dramatic enhancement in gel strength, while lactic acid (LACTEM) and acetic acid (ACETEM) esters produced only a marginal increase. Those additives which crystallized above 20 °C displayed pronounced changes in their network organization and crystal morphology in the presence of EC. Differences in the solid/liquid phase change behavior were also observed in select samples using differential scanning calorimetry. Both the small and large amplitude oscillatory shear responses were dependent on the ASM which was dependent on the chemistry of the headgroup, crystal network organization, and ability to plasticize the polymer network. The extent of thixotropic recovery was largely dependent on the polarity of functional groups in the ASMs, but was also influenced by the formation of a secondary crystal network. In general, ASMs which formed larger, system-spanning crystal networks (MAG, StAc) produced more brittle gels, while the highly hydrophilic, charged headgroup of SSL promoted a homogeneous distribution of small crystals, resulting in a tougher material. In the absence of a crystal network, stronger polar species in the ASM headgroup produced higher gel strength and increased elasticity. Thus, both ASM chemical structure and crystallization properties strongly contribute to the functionality of the resulting combined oleogelator systems.

BACKGROUND: There is considerable heterogeneity in fine particulate matter (PM2.5)-mortality associations between studies, potentially due to differences in exposure assessment methods. Our aim was to evaluate associations of PM2.5 predicted from different models with nonaccidental and cause-specific mortality. METHODS: We followed 107,906 participants of the Nurses Health Study cohort from 2001 to 2016. PM2.5 concentrations were estimated from spatiotemporal models developed by researchers at the University of Washington (UW), Pennsylvania State University (PSU), and Harvard TH Chan School of Public Health (HSPH). We calculated 12-month moving average concentrations and we used time-varying Cox proportional hazard ratios (HRs). RESULTS: There were 30,242 nonaccidental deaths in 1,435,098 person-years. We observed high correlations and similar temporal trends between the PM2.5 predictions. We found no associations of UW, PSU, or HSPH PM2.5 with nonaccidental mortality, but suggestive positive associations with cancer, cardiovascular, and respiratory disease mortality. There were small differences in HRs between the PM2.5 predictions. All three predictions showed the strongest associations with cancer mortality: HRs (95% confidence interval, expressed per 5 µg/m3 increase) were 1.06 (1.01, 1.12) for UW, 1.08 (1.03, 1.13) for PSU, and 1.05 (1.00, 1.10) for HSPH. In a subset restricted to participants who were always exposed to PM2.5 below 12 µg/m3, we observed positive associations with nonaccidental mortality. CONCLUSION: We found that differences between PM2.5 exposure assessment methods could lead to minor differences in strengths of associations between PM2.5 and cause-specific mortality in a population of US female nurses.

Superior mesenteric artery (SMA) pseudoaneurysm with superior mesenteric arteriovenous fistula (SMAVF) is a rare pathology associated with high rates of rupture and mortality. Known interventions for the treatment of SMA pseudoaneurysm with SMAVF include open repair or endovascular repair with coil embolization or covered stenting. To the best of our knowledge, this report is the first of physician-modified endograft for the treatment of SMA pseudoaneurysm with SMAVF after prior thrombosis, ligation, and coil embolization of the SMA. The patient recovered well and has 1 month of follow-up after the procedure.

We provide a new characterization of both belief update and belief revision in terms of a Kripke-Lewis semantics. We consider frames consisting of a set of states, a Kripke belief relation and a Lewis selection function. Adding a valuation to a frame yields a model. Given a model and a state, we identify the initial belief set K with the set of formulas that are believed at that state and we identify either the updated belief set K⋄ϕ or the revised belief set K⁎ϕ (prompted by the input represented by formula ϕ) as the set of formulas that are the consequent of conditionals that (1) are believed at that state and (2) have ϕ as antecedent. We show that this class of models characterizes both the Katsuno-Mendelzon (KM) belief update functions and the Alchourrón, Gärdenfors and Makinson (AGM) belief revision functions, in the following sense: (1) each model gives rise to a partial belief function that can be completed into a full KM/AGM update/revision function, and (2) for every KM/AGM update/revision function there is a model whose associated belief function coincides with it. The difference between update and revision can be reduced to two semantic properties that appear in a stronger form in revision relative to update, thus confirming the finding by Peppas et al. (1996) [30] that, “for a fixed theory K, revising K is much the same as updating K”. It is argued that the proposed semantic characterization brings into question the common interpretation of belief revision and update as change in beliefs in response to new information.