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Chronic low back pain is the most prevalent chronic pain condition worldwide and access to behavioral pain treatment is limited. Virtual reality (VR) is an immersive technology that may provide effective behavioral therapeutics for chronic pain. We aimed to conduct a double-blind, parallel-arm, single-cohort, remote, randomized placebo-controlled trial for a self-administered behavioral skills-based VR program in community-based individuals with self-reported chronic low back pain during the COVID-19 pandemic. A national online convenience sample of individuals with self-reported nonmalignant low back pain with duration of 6 months or more and with average pain intensity of 4 or more/10 was enrolled and randomized 1:1 to 1 of 2 daily (56-day) VR programs: (1) EaseVRx (immersive pain relief skills VR program); or (2) Sham VR (2D nature content delivered in a VR headset). Objective device use data and self-reported data were collected. The primary outcomes were the between-group effect of EaseVRx versus Sham VR across time points, and the between-within interaction effect representing the change in average pain intensity and pain-related interference with activity, stress, mood, and sleep over time (baseline to end-of-treatment at day 56). Secondary outcomes were global impression of change and change in physical function, sleep disturbance, pain self-efficacy, pain catastrophizing, pain acceptance, pain medication use, and user satisfaction. Analytic methods included intention-to-treat and a mixed-model framework. The study sample was 179 adults (female: 76.5%, 137/179; Caucasian: 90.5%, 162/179; at least some college education: 91.1%, 163/179; mean age: 51.5 years [SD 13.1]; average pain intensity: 5/10 [SD 1.2]; back pain duration ≥5 years: 67%, 120/179). No group differences were found for any baseline variable or treatment engagement. User satisfaction ratings were higher for EaseVRx versus Sham VR (P<.001). For the between-groups factor, EaseVRx was superior to Sham VR for all primary outcomes (highest P value=.009), and between-groups Cohen d effect sizes ranged from 0.40 to 0.49, indicating superiority was moderately clinically meaningful. For EaseVRx, large pre-post effect sizes ranged from 1.17 to 1.3 and met moderate to substantial clinical importance for reduced pain intensity and pain-related interference with activity, mood, and stress. Between-group comparisons for Physical Function and Sleep Disturbance showed superiority for the EaseVRx group versus the Sham VR group (P=.022 and .013, respectively). Pain catastrophizing, pain self-efficacy, pain acceptance, prescription opioid use (morphine milligram equivalent) did not reach statistical significance for either group. Use of over-the-counter analgesic use was reduced for EaseVRx (P<.01) but not for Sham VR. EaseVRx had high user satisfaction and superior and clinically meaningful symptom reduction for average pain intensity and pain-related interference with activity, mood, and stress compared to sham VR. Additional research is needed to determine durability of treatment effects and to characterize mechanisms of treatment effects. Home-based VR may expand access to effective and on-demand nonpharmacologic treatment for chronic low back pain. ClinicalTrials.gov NCT04415177; https://clinicaltrials.gov/ct2/show/NCT04415177. RR2-10.2196/25291.

Carbamoyl phosphate synthetase-1 (CPS1) is the major mitochondrial urea cycle enzyme in hepatocytes. It is released into mouse and human blood during acute liver injury, where is has a short half-life. The function of CPS1 in blood and the reason for its short half-life in serum are unknown. We show that CPS1 is released normally into mouse and human bile, and pathologically into blood during acute liver injury. Other cytoplasmic and mitochondrial urea cycle enzymes are also found in normal mouse bile. Serum, bile, and purified CPS1 manifest sedimentation properties that overlap with extracellular vesicles, due to the propensity of CPS1 to aggregate despite being released primarily as a soluble protein. During liver injury, CPS1 in blood is rapidly sequestered by monocytes, leading to monocyte M2-polarization and homing to the liver independent of its enzyme activity. Recombinant CPS1 (rCPS1), but not control r-transferrin, increases hepatic macrophage numbers and phagocytic activity. Notably, rCPS1 does not activate hepatic macrophages directly; rather, it activates bone marrow and circulating monocytes that then home to the liver. rCPS1 administration prevents mouse liver damage induced by Fas ligand or acetaminophen, but this protection is absent in macrophage-deficient mice. Moreover, rCPS1 protects from acetaminophen-induced liver injury even when given therapeutically after injury induction. In summary, CPS1 is normally found in bile but is released by hepatocytes into blood upon liver damage. We demonstrate a nonenzymatic function of CPS1 as an antiinflammatory protective cytokine during acute liver injury.

\"This indispensable one-volume narrative examines the history, culture, environment, economy, politics, future, and more of the city of Tokyo, Japan's political and cultural capital.\" --Provided by publisher.

Lithium-metal battery (LMB) research and development has been ongoing for six decades across academia, industry and national laboratories. Despite this extensive effort, commercial LMBs have yet to displace, or offer a ready alternative to, lithium-ion batteries in electric vehicles (EVs). Here we explore some of the most critical industry needs that will have to be resolved to advance practical LMB designs for implementation in EVs. We begin our exploration with a brief overview of LMBs, then consider the following needs: energy density, anode thickness and cathode loading, electrolyte formulation and gas generation, electrolyte injection amount, cathode oxygen release, cell pressure control, cell format, cell manufacturing quality checks and battery modelling. We conclude with generic cell design recommendations for future LMB EV applications. Despite extensive research, lithium-metal batteries have not yet replaced lithium-ion batteries in electric vehicles. The authors explore critical industry needs for advancing lithium-metal battery designs for electric vehicles and conclude with cell design recommendations.

Informed behavior change as an HIV prevention tool has yielded unequal successes across populations. Despite decades of HIV education, some individuals remain at high risk. The mainstream media often portrays these risk factors as products of race and national borders; however, a rich body of recent literature proposes a host of complex social factors that influence behavior, including, but not limited to: poverty, income inequality, stigmatizing social institutions and health care access. We examined the relationship between numerous social indicators and HIV incidence across eighty large U.S. cities in 1990 and 2000. During this time, major correlating factors included income inequality, poverty, educational attainment, residential segregation and marriage rates. However, these ecological factors were weighted differentially across risk groups (e.g. heterosexual, intravenous drug use, men who have sex with men (MSM)). Heterosexual risk rose significantly with poor economic indicators, while MSM risk depended more heavily on anti-homosexual stigma (as measured by same-sex marriage laws). HIV incidence among black individuals correlated significantly with numerous economic factors but also with segregation and imbalances in the male:female ratio (often an effect of mass incarceration). Our results support an overall model of HIV ecology where poverty, income inequality and social inequality (in the form of institutionalized racism and anti-homosexual stigma) have over time developed into synergistic drivers of disease transmission in the U.S., inhibiting information-based prevention efforts. The relative weights of these distal factors vary over time and by HIV risk group. Our testable model may be more generally applicable within the U.S. and beyond.

Confined samples of liquid crystals are characterized by a variety of topological defects and can be exposed to external constraints such as extreme confinements with nontrivial topology. Here we explore the intrinsic structure of smectic colloidal layers dictated by the interplay between entropy and an imposed external topology. Considering an annular confinement as a basic example, a plethora of competing states is found with nontrivial defect structures ranging from laminar states to multiple smectic domains and arrays of edge dislocations, which we refer to as Shubnikov states in formal analogy to the characteristic of type-II superconductors. Our particle-resolved results, gained by a combination of real-space microscopy of thermal colloidal rods and fundamental-measure-based density functional theory of hard anisotropic bodies, agree on a quantitative level. Colloidal rod-like mesogens make the study of liquid crystal structures available to simple optical microscopy. Wittmann et al. study topological defects in smectic phases under annular confinement and reveal a remarkable, quantitative agreement with a theoretic density functional description.