Isolation and Identification of Human Gut Bacteria Capable of Converting Curcumin to Its Hydrogenated Metabolites.

Curcumin is widely recognized for its health benefits, though the role of gut microbiota in its metabolic transformation was not well studied. In this study, bacterial strains capable of metabolizing curcumin were isolated from human stool samples. Using 16S rRNA and whole-genome sequencing, two novel strains (Clostridium butyricum UMA_cur1 and Escherichia coli UMA_cur2) were identified. In addition, the metabolic products were analyzed using liquid chromatography-mass spectrometry. These strains efficiently converted curcumin into dihydro-curcumin (DHC) and tetrahydro-curcumin (THC). Notably, E. coli UMA_cur2 also produced hexahydro-curcumin (HHC) and octahydro-curcumin (OHC), marking the first identification of a strain capable of such transformations. The absence of the YncB gene (typically involved in curcumin conversion) in C. butyricum UMA_cur1 suggests an alternative metabolic pathway. Curcumin metabolism begins during the stationary growth phase, indicating that it is not crucial for primary growth functions. Furthermore, E. coli UMA_cur2 produced these metabolites sequentially, starting with DHC and THC and progressing to HHC and OHC. These findings identified two novel strains that can metabolize curcumin to hydrogenated metabolites, which enhance our understanding of the interaction between curcumin and gut microbiota.

Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral Replication and Nonlethal Disease Progression.

Many mouse models of SARS-CoV-2 infection involve expression of the human ACE2 protein, the entry receptor for SARS-CoV-2 Spike protein, in mouse tissues. However, most of these models suffer from nonphysiological regulation of ACE2 expression, which can lead to atypically severe infections and aberrant sites of viral replication. In this report, we developed and characterized an ACE2 gene replacement (ACE2-GR) mouse strain in which the mouse Ace2 genomic locus was replaced by the entire human ACE2 gene locus, and we investigated the ability of these animals to respond to SARS-CoV-2 infection. We show that ACE2-GR mice support SARS-CoV-2 viral replication, but, in stark contrast to the widely used K18-hACE2 transgenic model, this infection leads to a mild disease with no detectable involvement of the CNS. Thus, ACE2-GR mice provide a novel, to our knowledge, model to explore immune responses and long-term consequences of SARS-CoV-2 infection.

Impact of Integrative Health and Medicine on Costs Associated with Adult Health System Beneficiaries with Musculoskeletal Conditions: A Retrospective Cohort Study.

Objective: Owing to perceived additional costs, patients may avoid integrative health and medicine (IHM) treatments, while insurers may not cover IHM. We hypothesized that adult beneficiaries of a health system's employee insurance plan with musculoskeletal (MSK) conditions receiving covered outpatient IHM would have reduced total allowed costs over the 1-year follow-up compared with matched controls, secondarily exploring medical and pharmaceutical cost subsets. Methods: We queried medical records and claims spanning 2018-2023 for beneficiaries aged 18-89 years with a new MSK episode. Patients were divided into cohorts: (1) IHM within 3 months after MSK diagnosis and (2) no IHM after initial primary care. After inflation adjustment and trimming, propensity score matching was used to balance cohorts on demographics, comorbidity, health care utilization, and prior 12-month spend. Least-squares mean total, medical, and pharmaceutical allowed costs (United States Dollar) over the 1-year follow-up were analyzed using a linear mixed model. Findings were compared with a generalized linear model without trimming. Results: There were 251 patients per matched cohort, with adequate covariate balance. There was no meaningful between-cohort difference (IHM minus No IHM) in least-squares mean total cost (+703 [95% CI: -314, 1720]). Secondary outcomes included medical cost (+878 [95% CI: 61, 1695]) and pharmaceutical cost (+6 [95% CI: -71, 83]). A generalized linear model revealed no meaningful difference in estimated mean total medical costs (-2561 [95% CI: -7346, +2224]). Conclusions: IHM use among adult health system beneficiaries with MSK conditions was not associated with meaningful differences in 1-year follow-up total health care costs compared with matched controls. Our study was underpowered for secondary outcomes, which should be interpreted with caution. Future research should include a larger sample of patients and examine longitudinal changes in patient-reported outcomes.

Value-Based Radiology in Canada: Reducing Low-Value Care and Improving System Efficiency.

Radiology departments are increasingly tasked with managing growing demands on services including long waitlists for scanning and interventional procedures, human health resource shortages, equipment needs, and challenges incorporating advanced imaging solutions. The burden of system inefficiencies and the overuse of "low-value" imaging causes downstream impact on patients at the individual level, the economy and healthcare system at the societal level, and planetary health at an overarching level. Low value imaging includes those performed for an inappropriate clinical indication, with little to no value to the management of the patient, and resulting in healthcare resource waste; it is estimated that up to a quarter of advanced imaging studies in Canada meet this criterion. Strategies to reduce low-value imaging include the development and use of referral guidelines, use of appropriateness criteria, optimization of existing protocols, and integration of clinical decision support tools into the ordering provider's workflow. Additional means of optimizing system efficiency such as centralized intake models, improved access to electronic medical records and outside imaging, enhanced communication with patients and referrers, and the utilization of artificial intelligence will further increase the value of radiology provided to patients and care providers.

CD4 + T cells recruit, then engage macrophages in cognate interactions to clear Mycobacterium tuberculosis from the lungs.

IFN-γ-producing CD4 + T cells are required for protection against lethal Mycobacterium tuberculosis ( Mtb ) infections. However, the ability of CD4 + T cells to suppress Mtb growth cannot be fully explained by IFN-γ or other known T cell products. In this study, we show that CD4 + T cell-derived IFN-γ promoted the recruitment of monocyte-derived macrophages (MDMs) to the lungs of Mtb -infected mice. Although the recruited MDMs became quickly and preferentially infected with Mtb , CD4 + T cells rapidly disinfected the MDMs. Clearance of Mtb from MDMs was not explained by IFN-γ, but rather by MHCII-mediated cognate interactions with CD4 + T cells. These interactions promoted MDM expression of glycolysis genes essential for Mtb control. Thus, by recruiting MDMs, CD4 + T cells initiate a cycle of bacterial phagocytosis, Mtb antigen presentation and disinfection in an attempt to clear the bacteria from the lungs.

Post-traumatic Total Hip Arthroplasty After Acetabular Fractures: Benefits of the Hardinge Approach.

Post-traumatic arthritis is a common sequelae after undergoing open reduction and internal fixation (ORIF) of acetabular fractures. This often necessitates conversion to total hip arthroplasty (THA) to help alleviate pain and improve function for these patients. Unfortunately, dislocation rates for post-traumatic THA have been alarmingly high especially when the posterior approach has been used. In the setting of prior soft tissue disruption, the theoretical risk of dislocation is even greater. Conversely, the lateral or the abductor-split approach (Hardinge) is associated with decreased dislocation rates. In this retrospective case series, we evaluated the dislocation rate of the Hardinge approach on patients who underwent THA after developing post-traumatic arthritis after acetabulum ORIF. All patients who matched CPT code 27132 (Repair, Revision, and/or Reconstruction Procedures on the Pelvis and Hip Joint), from January 2009 to December 2019, and treated by the senior author, were pulled from the electronic medical record at the University of Pittsburgh Medical Center. Thirty-one of the resultant 110 were treated with THA for post-traumatic arthrosis through a lateral, abductor-splitting Hardinge approach and met the inclusion criteria for further study. Our case series involves 31 patients who underwent post-traumatic THA through a Hardinge approach: the mean age at the time of index acetabular ORIF is 48.5 years, the mean age at the time of THA is 53.5 years, and the mean interval between ORIF and ultimate THA was five years. The mean length of follow-up after THA was 22.4 months. Overall, patients did well with an all-cause revision rate of 9.7%, with no revision performed for loosening of either the acetabular or femoral component. One patient developed an infection. No patient in our group sustained a dislocation, and all implants were stable without evidence of radiographic loosening at the final follow-up. This study found satisfactory results with patients undergoing THA via lateral or abductor split approach (Hardinge) for post-traumatic arthritis after acetabular ORIF. The use of a Hardinge approach for post-traumatic reconstruction of the hip may be protective against dislocation without increasing baseline risks in this difficult patient population.

Psychotherapy dose, clinical outcome, and academic withdrawal at university counseling centers.

Academic withdrawal from colleges and universities is a common occurrence, particularly among students with mental health concerns. Receiving a successful course of psychotherapy may reduce students' risk of academic withdrawal, but outcomes in university counseling centers (UCCs) could be hindered by strategies used to meet high service demands with limited resources, such as offering a low number or frequency of sessions. The present study examined associations among psychotherapy dose, clinical outcome, and academic withdrawal among students (N = 16,197) in short-term individual psychotherapy at 85 UCCs in the United States. Structural equation modeling results indicated that after controlling for baseline psychological distress, the number of psychotherapy sessions attended positively predicted, and the average number of days between sessions negatively predicted, clients' self-reported reductions in psychological distress. In turn, after controlling for pretreatment characteristics associated with academic withdrawal (prior psychiatric hospitalization, gender, academic distress) reductions in psychological distress negatively predicted therapists' report of clients voluntarily withdrawing from their academic institution during psychotherapy. This indicates that students who receive higher psychotherapy doses within a short-term context (i.e., 10 or fewer sessions) are less distressed by the end of treatment, which then predicts a lower likelihood of academic withdrawal during psychotherapy. UCC leadership and clinicians might enhance clinical and academic outcomes by providing flexibility in the number and frequency of psychotherapy sessions available to students. However, centers may need additional resources from their academic institutions to provide this flexibility. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Structure-Activity Relationship Studies in Benzothiadiazoles as Novel Vaccine Adjuvants.

Extracellular vesicles (EVs) can transfer antigens and immunomodulatory molecules, and such EVs released by antigen-presenting cells equipped with immunostimulatory functions have been utilized for vaccine formulations. A prior high-throughput screening campaign led to the identification of compound 634 (1), which enhanced EV release and increased intracellular Ca2+ influx. Here, we performed systematic structure-activity relationship (SAR) studies to investigate the scaffold for its potency as a vaccine adjuvant. Synthesized compounds were analyzed in vitro for CD63 reporter activity (a marker for EV biogenesis) in human THP-1 cells, induction of Ca2+ influx, IL-12 production, and cell viability in murine bone-marrow-derived dendritic cells. The SAR studies indicated that the ester functional group was requisite, and the sulfur atom of the benzothiadiazole ring replaced with a higher selenium atom (9f) or a bioisosteric ethenyl group (9h) retained potency. Proof-of-concept vaccination studies validated the potency of the selected compounds as novel vaccine adjuvants.

The C-Brace® microprocessor controlled stance and swing orthosis improves safety, mobility, and quality of life at one year: Interim results from a prospective registry.

Introduction: The C-Brace microprocessor-controlled stance and swing control orthosis has been shown to improve function, mobility, and quality of life. A systematic registry to gather long-term, real-world safety and effectiveness data in patients fit with a C-Brace has not been performed. Methods: International multicenter registry. Patients undergoing routine C-Brace fittings were assessed at baseline and 1 year after fitting. Primary outcomes were fast walking speed (FWS) measured by 25-foot or 10-meter walk test, Timed Up and Go (TUG) and the Activity-specific Balance Confidence (ABC) Scale. Secondary and exploratory outcomes included the Patient-specific Functional Scale (PSFS), falls, pain, PROMIS Pain Interference (PI), and quality of life. Results: 48 subjects with 1-year baseline and follow up data were analyzed. With the C-Brace, FWS improved by + 0.26 ± 0.33 m/s (p < .0001), TUG by -8.1 ± 14.6 sec (p < .0001), and ABC by + 24.9 ± 25.8% (p < .0001). Mean falls reduced from 33 ± 77 to 3.0 ± 5.6 (p = .0005). PSFS increased by 3.60 ± 2.34 points (p < .0001). Outcomes for pain, PI and quality of life showed significant improvements with the C-Brace. Conclusion: The C-Brace is an effective option to improve safety, mobility, and quality of life for patients needing a KAFO for ambulation.

Microclimate and thermal refuge influences on sage-grouse brood habitat selection.

Wildlife space use is driven by three primary mechanisms, predator avoidance, foraging, and thermoregulation. The latter has largely been overlooked in wildlife research. Understanding how habitat use is influenced by thermoregulatory properties is a critical component to depicting species' ecology. Galliformes' (i.e., ground nesting birds with precocial young) ecology is predisposed to thermal extremes, where newly hatched chicks are unable to thermoregulate <14 d post-hatch, and have limited capabilities until >21 d post-hatch. We examined greater sage-grouse (Centrocercus urophasianus) brood rearing habitats and provide the first evaluation as to how microscale thermal environments influenced habitat selection. We monitored 24 broods, collected 82,929 black bulb temperature measurements from thermal arrays (n = 256) comprised of stainless steel black bulbs (i.e., surrogate for operative temperature) to compare brood morning (i.e., foraging, n = 78), afternoon (i.e., loafing, n = 82) and associated random locations (n = 96) between early (≤21 d post-hatch) and late (>21 d post-hatch) brood-rearing. We measured vegetation at all locations to disentangle relationships between cover and thermoregulatory metrics. We found that microclimates at all foraging locations heated more rapidly than either their loafing or random locations. Alternatively, loafing locations moderated ambient temperature more effectively than foraging locations but were similar to random locations. Broods were using loafing sites that both increased their ability to avoid predators (i.e., increased shrub structure) and buffered ambient temperature better than their foraging locations. Interestingly, random afternoon locations tended to lack concealment from predators, despite these locations showing improved thermal buffering compared to foraging locations. However, early brood-rearing habitats appeared to moderate ambient temperatures more effectively than late. Our results suggested that managing vegetation for structural heterogeneity will afford a diversity of thermal refuge for greater sage-grouse broods during this critical life history stage.

Gas and particle emissions from rifle and pistol firing.

Emissions were sampled from firing an M4 carbine rifle and a M9 (military issue of Beretta 75 FS 9 mm pistol) to develop sampling methods and assess potential exposures and range contamination issues. Breech and muzzle emissions were sampled from the rifle when firing M855A1 ammunition (lead (Pb)-free slugs) in single- and triple-shot burst mode and from single pistol shots when firing 9 mm XM1152 ammunition (not Pb-free). Emissions were sampled for carbon monoxide (CO), carbon dioxide (CO2), methane, hydrogen cyanide, ammonia, particulate matter by size, polycylic aromatic hydrocarbons, and volatile organics. Analyses on the particles included elemental composition, size distribution, carbon composition (black, total, organic, and elemental carbon), and particle composition and morphology. Emission concentrations from both the rifle and pistol were characterized by CO/CO2 ratios between, approximately, 1/1 and 2/1, respectfully, indicating incomplete carbon oxidation. The initial particle size distribution was dominated in number by particles smaller than 40 nm but the high particle concentrations led to rapid agglomeration. The abundance of CO and metals of inhalable particle size are noteworthy and indicate that further assessment of exposure would determine potential inhalation health hazards, particularly in indoor firing ranges.

Chemical mutagenesis of Listeria monocytogenes for increased tolerance to benzalkonium chloride shows independent genetic underpinnings and off-target antibiotic resistance.

Listeria monocytogenes, a potentially fatal foodborne pathogen commonly found in food processing facilities, creates a significant economic burden that totals more than $2 billion annually in the United States due to outbreaks. Quaternary ammonium compounds (QACs), including benzalkonium chloride (BAC), are among the most widely used sanitizers to inhibit the growth and spread of L. monocytogenes from food processing facilities. However, resistance to QACs has been increasing in L. monocytogenes and different genetic mechanisms conferring resistance have been discovered. Here, we used ethyl methanesulfonate (EMS) to chemically mutagenize the BAC-susceptible strain, L. monocytogenes FSL-N1-304. We isolated two mutants with increased tolerance to BAC compared to the parental strain. Next, we assessed the off-target effect of increased tolerance to BAC by measuring the minimum inhibitory concentrations (MICs) of a diverse set of antibiotics, revealing that mut-1 and mut-2 displayed significantly increased resistance to fluoroquinolone antibiotics compared to the parental strain. A hemolysis assay was then used to investigate a potential correlation between BAC tolerance and virulence. Interestingly, mut-1 and mut-2 both exhibited significantly higher hemolysis percentage than the parental strain. We then sequenced the genomes of the parental strain and both mutants to identify mutations that may be involved in the increased resistance to BAC. We identified 3 and 29 mutations in mut-1 and mut-2, respectively. mut-1 contained nonsynonymous mutations in dagK (a diacylglycerol kinase), lmo2768 (a permease-encoding gene), and lmo0186 (resuscitation promoting factor). mut-2 contained a nonsense mutation in the nucleotide excision repair enzyme UvrABC system protein B encoding gene, uvrB, which likely accounts for the higher number of mutations observed. Transcriptome analysis in the presence of BAC revealed that genes related to the phosphotransferase system and internalins were up-regulated in both mutants, suggesting their significance in the BAC stress response. These two mutants provide insights into alternative mechanisms for increased BAC tolerance and could further our understanding of how L. monocytogenes persists in the food processing environment.

Dynamics in Cre-loxP site-specific recombination.

Cre recombinase is a phage-derived enzyme that has found utility for precise manipulation of DNA sequences. Cre recognizes and recombines pairs of loxP sequences characterized by an inverted repeat and asymmetric spacer. Cre cleaves and religates its DNA targets such that error-prone repair pathways are not required to generate intact DNA products. Major obstacles to broader applications are lack of knowledge of how Cre recognizes its targets, and how its activity is controlled. The picture emerging from high resolution methods is that the dynamic properties of both the enzyme and its DNA target are important determinants of its activity in both sequence recognition and DNA cleavage. Improved understanding of the role of dynamics in the key steps along the pathway of Cre-loxP recombination should significantly advance our ability to both redirect Cre to new sequences and to control its DNA cleavage activity in the test tube and in cells.

The effect of SARS-CoV-2 on the incidence of post-operative venous sinus thrombosis following skull base procedures.

PURPOSE: Sinus thrombosis is a common post-operative finding after posterior fossa surgery performed in the vicinity of the dural venous sinuses. The SARS-CoV-2 virus has been shown to confer an increased risk of venous thromboembolic events owing to eliciting a hyper-inflammatory and pro-thrombotic state. In this study, we examine the incidence of post-operative venous sinus thrombosis in patients undergoing peri-sigmoid posterior fossa surgery in the pre- and post-COVID era and investigate whether COVID infection confers an increased risk of sinus thrombosis. METHODS: A retrospective review of a single institution case series of patients underwent peri-sigmoid surgery (retrosigmoid, translabyrinthine, or far lateral) approach. Relevant clinical variables were investigated that may confer an increased risk of sinus thrombosis. RESULTS: A total of 311 patients (178 in the pre-COVID era, and 133 operated on after the pandemic began in March 2020) are included in the study. The composite incidence of sinus thrombosis seen on post-operative imaging was 7.8%. The incidence of sinus thrombosis in the pre-COVID cohort was N = 12 patients (6.7%) versus N = 12 (9%) in the post-COVID cohort (p = 0.46). A history of COVID infection was not shown to confer an increased risk of post-operative sinus thrombosis (OR: 0.61; 95% CI: 0.08-4.79, p = 0.64). Only a small number of patients (N = 7, 2.3%) required either medical or surgical intervention for post-operative sinus thrombosis. CONCLUSION: The overall incidence of post-operative sinus thrombosis is similar in the pre- and post-COVID era. The findings of this study suggest that COVID infection is not associated with a higher risk of venous sinus thrombosis.

Postoperative Cesarean Section Pain Management Using Transversus Abdominis Plane Block Versus Intrathecal Morphine: A Systematic Review and Meta-analysis.

PURPOSE: Compare and evaluate the effectiveness of transversus abdominis plane (TAP) block versus intrathecal morphine (ITM) on elective postcesarean section pain, opioid consumption, and related side effects. DESIGN: Systematic review and meta-analysis. METHODS: A search for evidence was conducted in PubMed, Google Scholar, CINAHL, Cochrane Collaboration Database, UpToDate, Health Source, and gray literature. Only randomized controlled trials (RCTs) were included in the study. The methodological quality of evidence assessment was conducted using the Risk of Bias and Grades of Recommendation, Assessment, Development, and Evaluation system. The meta-analysis used Review Manager (RevMan 5.4, The Cochrane Collaboration). FINDINGS: A total of 11 RCTs involving 1,129 patients were analyzed. Compared to ITM, TAP has a similar effect on static (mean difference [MD]; 0.37; 95% confidence interval [CI], -0.04 to 0.79; P = .08) and dynamic pain scores (MD, 0.43; 95% CI, -0.06 to 0.92; P = .09) within the first 48 hours after surgery. Additionally, the TAP block had a lower incidence of postoperative nausea and vomiting (risk ratio, 0.45; 95% CI, 0.31 to 0.66; P < .0001) and increased opioid consumption (MD, 6.78; 95% CI, 3.79 to 9.77; P < .00001). Overall, TAP block and ITM did not differ in the time to first to rescue analgesia, incidence of sedation, and pruritus. CONCLUSIONS: Evidence suggests that TAP blocks are equivalent to ITM in pain scores and more effective at lowering the incidence of postoperative nausea and vomiting, yet ITM has been shown to be more effective in reducing postoperative opioid consumption.

The fundamental role of character coding in Bayesian morphological phylogenetics.

Phylogenetic trees establish a historical context for the study of organismal form and function. Most phylogenetic trees are estimated using a model of evolution. For molecular data, modeling evolution is often based on biochemical observations about changes between character states. For example, there are four nucleotides, and we can make assumptions about the probability of transitions between them. By contrast, for morphological characters, we may not know a priori how many characters states there are per character, as both extant sampling and the fossil record may be highly incomplete, which leads to an observer bias. For a given character, the state space may be larger than what has been observed in the sample of taxa collected by the researcher. In this case, how many evolutionary rates are needed to even describe transitions between morphological character states may not be clear, potentially leading to model misspecification. To explore the impact of this model misspecification, we simulated character data with varying numbers of character states per character. We then used the data to estimate phylogenetic trees using models of evolution with the correct number of character states and an incorrect number of character states. The results of this study indicate that this observer bias may lead to phylogenetic error, particularly in the branch lengths of trees. If the state space is wrongly assumed to be too large, then we underestimate the branch lengths, and the opposite occurs when the state space is wrongly assumed to be too small.

Cardiovascular Responses to Occupational Physical Activity are Exaggerated by Work-Related Stress and Low Fitness.

OBJECTIVES: Paradoxical associations between high occupational physical activity (OPA) and cardiovascular disease may be explained by exaggerated cardiovascular responses from high work-related stress or low worker fitness. METHODS: OPA, blood pressure (BP), heart rate (HR), and rate-pressure product (HR x BP, RPP) were measured objectively for 24-hours in nineteen male workers. Work-related stress was measured using the Stress-in-General Scale. Fitness was estimated using a submaximal treadmill test. Effect modification by work-related stress and fitness on associations between OPA and cardiovascular responses was examined using mixed models with interactions. RESULTS: Associations between OPA and RPP, HR, and BP were stronger with high stress (p < 0.05). Associations of work-time MVPA and RPP were attenuated with higher fitness (p < 0.05). CONCLUSIONS: OPA performed under high work-related stress or by workers with low fitness may exaggerate cardiovascular responses to OPA.

Arrest History and Health Among U.S. Sexual and Gender Minority Youth, 2022.

INTRODUCTION: Sexual and gender minority youth, who experience high mental and behavioral health needs, are overrepresented in the criminal legal system, which may exacerbate these needs. This study examined the associations between arrest history and mental and behavioral health among sexual and gender minority youth. METHODS: Using cross-sectional survey data from the 2022 LGBTQ+ National Teen Survey, this study created a case-control sample of 287 sexual and gender minority youth with an arrest history and 1,148 propensity-matched sexual and gender minority youth without an arrest history. Associations between arrest history and sexual and gender minority developmental milestones, minority stressors, and mental and behavioral health outcomes were examined. Statistical analyses were conducted between 2022 and 2024. RESULTS: Arrest history was significantly associated with several sexual and gender minority developmental milestones (e.g., earlier age of identity realization and disclosure) and minority stressors (e.g., greater bullying and parental rejection). Sexual and gender minority youth with an arrest history had poorer mental and behavioral health, including greater sleep disturbance (AOR=1.46; 95% CI=1.08, 2.00) and positive screenings for depression (AOR=1.60; 95% CI=1.20, 2.14), anxiety (AOR=1.35; 95% CI=1.01, 1.82), and risk for substance use disorder development (AOR=5.81; 95% CI=4.26, 7.94). CONCLUSIONS: Arrest history is associated with the mental and behavioral health of sexual and gender minority youth, highlighting systemic inequities. Tailored public health interventions are needed to reduce criminal-legal contact in this population.

Adrenal gland macrophages regulate glucocorticoid production through Trem2 and TGF-ß.

Glucocorticoid synthesis by adrenal glands (AGs) is regulated by the hypothalamic-pituitary-adrenal axis to facilitate stress responses when the host is exposed to stimuli. Recent studies implicate macrophages as potential steroidogenic regulators, but the molecular mechanisms by which AG macrophages exert such influence remain unclear. In this study, we investigated the role of AG macrophages in response to cold challenge or atherosclerotic inflammation as physiologic models of acute or chronic stress. Using single-cell RNA sequencing, we observed dynamic AG macrophage polarization toward classical activation and lipid-associated phenotypes following acute or chronic stimulation. Among transcriptional alterations induced in macrophages, triggering receptor expressed on myeloid cells 2 (Trem2) was highlighted because of its upregulation following stress. Conditional deletion of macrophage Trem2 revealed a protective role in stress responses. Mechanistically, Trem2 deletion led to increased AG macrophage death, abolished the TGF-ß-producing capacity of AG macrophages, and resulted in enhanced glucocorticoid production. In addition, enhanced glucocorticoid production was replicated by blockade of TGF-ß signaling. Together, these observations suggest that AG macrophages restrict steroidogenesis through Trem2 and TGF-ß, which opens potential avenues for immunotherapeutic interventions to resolve stress-related disorders.

The Role of Electroencephalogram-Assessed Bandwidth Power in Response to Hypnotic Analgesia.

Research supports the efficacy of therapeutic hypnosis for reducing acute and chronic pain. However, little is known about the mechanisms underlying these effects. This paper provides a review of the evidence regarding the role that electroencephalogram-assessed bandwidth power has in identifying who might benefit the most from hypnotic analgesia and how these effects occur. Findings are discussed in terms of the slow wave hypothesis, which posits that brain activity in slower bandwidths (e.g., theta and alpha) can facilitate hypnosis responsivity. Although the extant research is limited by small sample sizes, the findings from this research are generally consistent with the slow wave hypothesis. More research, including and especially studies with larger sample sizes, is needed to confirm these preliminary positive findings.