Reducing gut microbiome-driven adipose tissue inflammation alleviates metabolic syndrome.

BACKGROUND: The gut microbiota contributes to macrophage-mediated inflammation in adipose tissue with consumption of an obesogenic diet, thus driving the development of metabolic syndrome. There is a need to identify and develop interventions that abrogate this condition. The hops-derived prenylated flavonoid xanthohumol (XN) and its semi-synthetic derivative tetrahydroxanthohumol (TXN) attenuate high-fat diet-induced obesity, hepatosteatosis, and metabolic syndrome in C57Bl/6J mice. This coincides with a decrease in pro-inflammatory gene expression in the gut and adipose tissue, together with alterations in the gut microbiota and bile acid composition. RESULTS: In this study, we integrated and interrogated multi-omics data from different organs with fecal 16S rRNA sequences and systemic metabolic phenotypic data using a Transkingdom Network Analysis. By incorporating cell type information from single-cell RNA-seq data, we discovered TXN attenuates macrophage inflammatory processes in adipose tissue. TXN treatment also reduced levels of inflammation-inducing microbes, such as Oscillibacter valericigenes, that lead to adverse metabolic phenotypes. Furthermore, in vitro validation in macrophage cell lines and in vivo mouse supplementation showed addition of O. valericigenes supernatant induced the expression of metabolic macrophage signature genes that are downregulated by TXN in vivo. CONCLUSIONS: Our findings establish an important mechanism by which TXN mitigates adverse phenotypic outcomes of diet-induced obesity and metabolic syndrome. TXN primarily reduces the abundance of pro-inflammatory gut microbes that can otherwise promote macrophage-associated inflammation in white adipose tissue. Video Abstract.

Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis.

Prescription of modified-release opioids for acute postoperative pain is widespread despite evidence to show their use may be associated with an increased risk of adverse effects. This systematic review and meta-analysis aimed to examine the available evidence on the safety and efficacy of modified-release, compared with immediate-release, oral opioids for postoperative pain in adults. We searched five electronic databases from 1 January 2003 to 1 January 2023. Published randomised clinical trials and observational studies on adults who underwent surgery which compared those who received oral modified-release opioids postoperatively with those receiving oral immediate-release opioids were included. Two reviewers independently extracted data on the primary outcomes of safety (incidence of adverse events) and efficacy (pain intensity, analgesic and opioid use, and physical function) and secondary outcomes (length of hospital stay, hospital readmission, psychological function, costs, and quality of life) up to 12 months postoperatively. Of the eight articles included, five were randomised clinical trials and three were observational studies. The overall quality of evidence was low. Modified-release opioid use was associated with a higher incidence of adverse events (n = 645, odds ratio (95%CI) 2.76 (1.52-5.04)) and worse pain (n = 550, standardised mean difference (95%CI) 0.2 (0.04-0.37)) compared with immediate-release opioid use following surgery. Our narrative synthesis concluded that modified-release opioids showed no superiority over immediate-release opioids for analgesic consumption, length of hospital stay, hospital readmissions or physical function after surgery. One study showed that modified-release opioid use is associated with higher rates of persistent postoperative opioid use compared with immediate-release opioid use. None of the included studies reported on psychological function, costs or quality of life.

Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study.

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3-13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.

Development and validation of a brief screener for posttraumatic stress disorder risk in emergency medical settings.

OBJECTIVE: Predicting risk of posttraumatic stress disorder (PTSD) in the acute care setting is challenging given the pace and acute care demands in the emergency department (ED) and the infeasibility of using time-consuming assessments. Currently, no accurate brief screening for long-term PTSD risk is routinely used in the ED. One instrument widely used in the ED is the 27-item Immediate Stress Reaction Checklist (ISRC). The aim of this study was to develop a short screener using a machine learning approach and to investigate whether accurate PTSD prediction in the ED can be achieved with substantially fewer items than the IRSC. METHOD: This prospective longitudinal cohort study examined the development and validation of a brief screening instrument in two independent samples, a model development sample (N = 253) and an external validation sample (N = 93). We used a feature selection algorithm to identify a minimal subset of features of the ISRC and tested this subset in a predictive model to investigate if we can accurately predict long-term PTSD outcomes. RESULTS: We were able to identify a reduced subset of 5 highly predictive features of the ISRC in the model development sample (AUC = 0.80), and we were able to validate those findings in the external validation sample (AUC = 0.84) to discriminate non-remitting vs. resilient trajectories. CONCLUSION: This study developed and validated a brief 5-item screener in the ED setting, which may help to improve the diagnostic process of PTSD in the acute care setting and help ED clinicians plan follow-up care when patients are still in contact with the healthcare system. This could reduce the burden on patients and decrease the risk of chronic PTSD.

The use of botulinum toxin in the acute management of symptomatic complex incisional hernia: a case series.

PURPOSE: Complications of incisional hernia are amongst the commonest presentations to the emergency surgical take. Outcomes from emergency hernia repair are poor, particularly for those with complex defects and for the growing population of comorbid, high-risk patients. Attempts to avoid emergency surgery by improving success rates of non-operative management could prove hugely beneficial. Botulinum toxin A (Botox) is already used in the elective management of incisional hernia and this study evaluates if the relaxation produced could be used to augment the outcomes of conservative management of acutely presenting incisional hernia. METHODS: Patients presenting between October 2020 and April 2022 without evidence of visceral ischaemia, who had been selected for a non-operative approach, were given 300 units of Botox under image guidance to the abdominal wall in addition to standard conservative measures. RESULTS: Twelve patients were eligible for Botox administration. Median age was 75 years and median BMI was 36.45 kg/m2. All patients were high risk; minimum ASA score was 3, and median frailty score was 5. In ten patients, symptoms resolved following Botox allowing for discharge without further complication. Seven subsequently referred on to the abdominal wall team. Symptoms did not settle in the two remaining patients; one required emergency laparotomy and the second was palliated. CONCLUSION: Botox may be a useful adjunct to established non-operative measures in patients with acute presentations of incisional hernia. It may improve the acute symptoms, eliminate the need for high-risk emergency surgery, or provide a bridge to abdominal wall reconstruction.

Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood.

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

Effect of discharge opioid on persistent postoperative opioid use: a retrospective cohort study comparing tapentadol with oxycodone.

Opioid harm can vary by opioid type. This observational study examined the effect of opioid type (oxycodone vs. tapentadol) on rates of persistent postoperative opioid use ('persistence'). We linked hospital and community pharmacy data for surgical patients who were dispensed discharge opioids between 1 January 2016 and 30 September 2021. Patients were grouped by opioid experience ('opioid-naive' having received no opioids in the 3 months before discharge) and formulation of discharge opioid (immediate release only or modified release ± immediate release). Mixed-effects logistic regression models predicted persistence (continued use of any opioid at 90 days after discharge), controlling for key persistence risk factors. Of the 122,836 patients, 2.31% opioid-naive and 27.24% opioid-experienced patients met the criteria for persistence. For opioid-naive patients receiving immediate release opioids, there was no significant effect of opioid type. Tapentadol modified release was associated with significantly lower odds of persistence compared with oxycodone modified release, OR (95%CI) 0.81 (0.69-0.94) for opioid-naive patients and 0.81 (0.71-0.93) for opioid-experienced patients. Among patients who underwent orthopaedic surgery (n = 19,832), regardless of opioid experience or opioid formulation, the odds of persistence were significantly lower for those who received tapentadol compared with oxycodone. This was one of the largest and most extensive studies of persistent postoperative opioid use, and the first that specifically examined persistence with tapentadol. There appeared to be lower odds of persistence for tapentadol compared with oxycodone among key subgroups, including patients prescribed modified release opioids and those undergoing orthopaedic surgery.

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Energetics of a Single Qubit Gate.

Qubits are physical, a quantum gate thus not only acts on the information carried by the qubit but also on its energy. What is then the corresponding flow of energy between the qubit and the controller that implements the gate? Here we exploit a superconducting platform to answer this question in the case of a quantum gate realized by a resonant drive field. During the gate, the superconducting qubit becomes entangled with the microwave drive pulse so that there is a quantum superposition between energy flows. We measure the energy change in the drive field conditioned on the outcome of a projective qubit measurement. We demonstrate that the drive's energy change associated with the measurement backaction can exceed by far the energy that can be extracted by the qubit. This can be understood by considering the qubit as a weak measurement apparatus of the driving field.

Parker Solar Probe Observations of Solar Wind Energetic Proton Beams Produced by Magnetic Reconnection in the Near-Sun Heliospheric Current Sheet.

We report observations of reconnection exhausts in the Heliospheric Current Sheet (HCS) during Parker Solar Probe Encounters 08 and 07, at 16 R s and 20 R s , respectively. Heliospheric current sheet (HCS) reconnection accelerated protons to almost twice the solar wind speed and increased the proton core energy by a factor of ∼3, due to the Alfvén speed being comparable to the solar wind flow speed at these near-Sun distances. Furthermore, protons were energized to super-thermal energies. During E08, energized protons were found to have leaked out of the exhaust along separatrix field lines, appearing as field-aligned energetic proton beams in a broad region outside the HCS. Concurrent dropouts of strahl electrons, indicating disconnection from the Sun, provide further evidence for the HCS being the source of the beams. Around the HCS in E07, there were also proton beams but without electron strahl dropouts, indicating that their origin was not the local HCS reconnection exhaust.

An approach to defining and achieving restoration targets for a threatened plant community.

Connecting scientific research and government policy is essential for achieving objectives in sustaining biodiversity in an economic context. Our approach to connecting theoretical ecology, applied ecology, and policy was devised using principles of restoration ecology and the requisite methodology to restore biodiverse ecosystems. Using a threatened ecological community (TEC) with >120 plant species, we posit our approach as a guide for interpreting and achieving regulatory compliance (i.e., government conditions) enacted to manage or offset environmental impacts of development. We inform the scientific approach necessary to delivering outcomes appropriate to policy intent and biodiverse restoration through theoretical and applied research into the ecological restoration of the highly endemic flora of banded ironstone formations of the Mid West of Western Australia. Our approach (1) defines scale-appropriate restoration targets that meet regulatory compliance (e.g., Government of Western Australia Ministerial Conditions); (2) determines the optimal method to return individual plant species to the restoration landscape; (3) develops a conceptual model for our system, based on existing restoration frameworks, to optimize and facilitate the pathway to the restoration of a vegetation community (e.g., TEC) using diverse research approaches; and (4) develops an assessment protocol to compare restoration achievements against the expected regulatory outcomes using our experimental restoration trials as a test example. Our approach systematically addressed the complex challenges in setting and achieving restoration targets for an entire vegetation community, a first for a semiarid environment. We interpret our approach as an industry application relevant to policy- or regulator-mediated mine restoration programs that seek to return biodiverse species assemblages at landscape scales.

Postmortem Diagnostic Overshadowing: Reporting Cerebral Palsy on Death Certificates.

Postmortem diagnostic overshadowing-defined as inaccurately reporting a disability as the underlying cause of death-occurs for over half of adults with cerebral palsy. This practice obscures cause of death trends, reducing the effectiveness of efforts to reduce premature mortality among this marginalized health population. Using data from the National Vital Statistics System 2005 to 2017 U.S. Multiple Cause of Death files (N = 29,996), we identify factors (sociodemographic characteristics, aspects of the context and processing of death, and comorbidities) associated with the inaccurate reporting of cerebral palsy as the underlying cause of death. Results suggest that inaccurate reporting is associated with heightened contexts of clinical uncertainty, the false equivalence of disability and health, and potential racial-ethnic bias. Ending postmortem diagnostic overshadowing will require training on disability and health for those certifying death certificates and efforts to redress ableist death certification policies.

Cause of death trends among adults with and without cerebral palsy in the United States, 2013-2017.

BACKGROUND: Adults with cerebral palsy (CP) in the United States die much earlier than those without CP, a health inequality likely shaped by causes of death. Existing research has not considered demographic differences in mortality patterns. OBJECTIVES: To analyze differences in cause of death for adults who did/did not have CP reported on their death certificates and to assess sex and racial-ethnic difference in causes of death among adult decedents with CP. METHODS: Data are from the 2013-2017 US Multiple Cause of Death Mortality files (N = 13,332,871; n = 13,897 with CP). Multiple logistic regression models were used to compare differences in causes of death between adults with and without CP and to determine sex and racial-ethnic differences in causes of death among adults with CP. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated. RESULTS: As compared with decedents without CP, those with CP were more likely to die from pneumonitis (aOR 31.14, 95% CI 29.42-32.96), influenza/pneumonia (8.78, 8.30-9.29), respiratory failure (17.24, 15.19-18.69), and choking (20.66, 18.86-22.62) and less likely to die from heart disease (0.61, 0.58-0.65), cancer (0.12, 0.11-0.13), chronic lower respiratory diseases (0.50, 0.44-0.56), and cerebrovascular diseases (0.66, 0.59-0.75). Among adults with CP, female decedents were more likely than males to die from respiratory failure (1.21, 1.03-1.42), and non-Hispanic Black decedents were more likely than non-Hispanic White decedents to die from heart disease (1.24, 1.07-1.45) and cerebrovascular disease (1.77, 1.29-2.49). CONCLUSIONS: In 2013-2017, heart disease was the leading cause of death for adults with and without CP. However, for people with compared to those without CP, likelihood of death from likely preventable respiratory causes of death was higher. Non-Hispanic Black adults were more likely than non-Hispanic White adults to die from heart and cerebrovascular diseases. Public health, clinical, and rehabilitation efforts must use a multifaceted approach to address respiratory and circulatory health among people with CP. DATABASE: United States National Vital Statistics System of the Centers for Disease Control and Prevention Multiple Cause of Death Mortality files (National Bureau of Economic Research: https://www.nber.org/research/data/vital-statistics-mortality-data-nber).

Evidence for widespread changes in the structure, composition, and fire regimes of western North American forests.

Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.