Smoking cessation in pregnant women using financial incentives: a feasibility study.

BACKGROUND: The high prevalence of smoking pregnant women in Dutch areas with lower socioeconomic status and the consecutively harmful exposure to tobacco to both mother and child, depicted a high need for a novel intervention. According to other studies, the utilisation of financial incentives appeared to be a promising method for smoking cessation in pregnant women. Therefore, the aim of this study was to investigate the feasibility of implementing contingent financial incentives as smoking cessation support for pregnant women in the Netherlands. METHODS: Feasibility study consisting of four developmental phases: (1) acceptability of Dutch population regarding financial-incentive-intervention by conducting an online questionnaire, (2) composing a pilot study utilising the financial-incentive-intervention in clinical practice, (3) execution of the composed pilot study and (4) evaluation of the executed pilot study utilising a mixed-methods approach. A financial-incentive-intervention, given in a contingent financial scheme (during five consequential appointments, respectively €25/€50/€100/€150/€250), if smoking abstinence was proven by the amount of cotinine in the urine of the pregnant women measured utilising a urine dipstick test. The public acceptability for the financial-incentive-intervention was assessed using 5-Likert scales. The number of pregnant women able to abstain from smoking during the pilot study and utilising the financial-incentive-intervention in clinical practice were used to assess the prosperity and practicality of the pilot study respectively. The pilot study was evaluated using a mixed-methods approach. RESULTS: In total, 55.1% of the Dutch population sample (n = 328) found a financial incentive inappropriate for smoking cessation in pregnant women, while the healthcare professionals and pilot study participants thought the financial-incentive-intervention to be a helpful approach. Eleven vouchers were given during the pilot study, and one woman completed all test points and tested negative for cotinine at the end of the pilot study. CONCLUSION: Although the financial-incentive-intervention appeared to be a promising approach for smoking cessation in pregnant women, the acceptability of the Dutch population and the number of pregnant women able to abstain smoking during this pilot study was low. Despite the limited study population, this study proved the concept of this financial-incentive-intervention to be feasible for implementation in the Netherlands. TRIAL REGISTRATION: Not applicable since this is a feasibility study prior to a trial.

Threshold-dependent iodine imaging and spectral separation in a whole-body photon-counting CT system.

OBJECTIVE: To evaluate the dual-energy (DE) performance and spectral separation with respect to iodine imaging in a photon-counting CT (PCCT) and compare it to dual-source CT (DSCT) DE imaging. METHODS: A semi-anthropomorphic phantom extendable with fat rings equipped with iodine vials is measured in an experimental PCCT. The system comprises a PC detector with two energy bins (20 keV, T) and (T, eU) with threshold T and tube voltage U. Measurements using the PCCT are performed at all available tube voltages (80 to 140 kV) and threshold settings (50-90 keV). Further measurements are performed using a conventional energy-integrating DSCT. Spectral separation is quantified as the relative contrast media ratio R between the energy bins and low/high images. Image noise and dose-normalized contrast-to-noise ratio (CNRD) are evaluated in resulting iodine images. All results are validated in a post-mortem angiography study. RESULTS: R of the PC detector varies between 1.2 and 2.6 and increases with higher thresholds and higher tube voltage. Reference R of the EI DSCT is found as 2.20 on average overall phantoms. Maximum CNRD in iodine images is found for T = 60/65/70/70 keV for 80/100/120/140 kV. The highest CNRD of the PCCT is obtained using 140 kV and is decreasing with decreasing tube voltage. All results could be confirmed in the post-mortem angiography study. CONCLUSION: Intrinsically acquired DE data are able to provide iodine images similar to conventional DSCT. However, PCCT thresholds should be chosen with respect to tube voltage to maximize image quality in retrospectively derived image sets. KEY POINTS: • Photon-counting CT allows for the computation of iodine images with similar quality compared to conventional dual-source dual-energy CT. • Thresholds should be chosen as a function of the tube voltage to maximize iodine contrast-to-noise ratio in derived image sets. • Image quality of retrospectively computed image sets can be maximized using optimized threshold settings.

Photon-counting detectors in computed tomography: from quantum physics to clinical practice.

Over the last decade, a fundamentally new type of computed tomography (CT) detectors has proved its superior capabilities in both physical and preclinical evaluations and is now approaching the stage of clinical practice. These detectors are able to discriminate single photons and quantify their energy and are hence called photon-counting detectors. Among the promising benefits of this technology are improved radiation dose efficiency, increased contrast-to-noise ratio, reduced metal artifacts, improved spatial resolution, simultaneous multi-energy acquisitions, and the prospect of multi-phase imaging within a single acquisition using multiple contrast agents. Taking the conventional energy-integrating detectors as a reference, the authors demonstrate the technical principles of this new technology and provide phantom and patient images acquired by a whole-body photon-counting CT. These images serve as a basis for discussing the potential future of clinical CT.

[Diagnosis and management of liver cysts]. / Diagnostic et traitement des kystes hépatiques.

Cystic hepatic lesions are frequent and sometimes large. They are generally asymptomatic and discovered by chance. The differential diagnosis of these lesions includes congenital, post-traumatic, benign or malignant tumors, as well as infectious pathologies. Conventional or contrast ultrasonography, abdominal computed tomography and magnetic resonance imaging can be used to characterize them. Therapeutic abstention with or without iconographic monitoring constitutes the optimal management of many benign liver cysts without clinical repercussions. Treatments for symptomatic or potentially aggressive lesions may include fenestration, puncture with sclerotherapy, or surgical resection. In this article, the authors discuss how to diagnose and treat the various hepatic cystic lesions.

Les lésions kystiques hépatiques sont fréquentes et parfois volumineuses. Elles sont généralement asymptomatiques et de découverte fortuite. Le diagnostic différentiel de ces lésions inclut des pathologies congénitales, post-traumatiques, tumorales bénignes ou malignes ainsi qu'infectieuses. L'échographie conventionnelle ou avec contraste, le scanner abdominal et la résonance magnétique nucléaire peuvent être utilisés pour les caractériser. L'abstention thérapeutique, avec ou sans surveillance iconographique, constitue la prise en charge optimale de nombreux kystes bénins sans répercussion clinique. Les traitements des lésions symptomatiques ou potentiellement agressives peuvent inclure la fenestration, la ponction avec sclérothérapie ou la résection chirurgicale. Dans cet article, les auteurs discutent des modalités de diagnostic et de traitement des diverses lésions kystiques hépatiques.

Role legitimacy, comfort and confidence providing tobacco, alcohol and other drug care: a cross-sectional study of Australian early-career general practitioners.

Australian general practitioners (GPs) see most Australians each year and, as tobacco, alcohol and other drug use (substance use) are common, GPs often see problematic, risky or dependent substance use. This study aimed to explore early-career GPs' role legitimacy, comfort and confidence managing patients with problematic use of tobacco, alcohol, psychoactive pharmaceutical or illicit substances.Using the '5A's framework: Ask, Assess, Advise, Assist and Arrange, we surveyed 251 early-career GPs (GP registrars) on role legitimacy, confidence managing patient substance use, and sources of clinical information, advice and support.There was strong agreement that managing substance use is a GP's role, with high levels of confidence 'Asking' (screening) about tobacco and alcohol use, which decreased across other substance classes. Early-career GPs reported lower levels of confidence 'Assessing' and 'Advising' (brief interventions); and much lower levels of confidence 'Assisting' (treating) and 'Arranging' (follow up and/or referral) for patients with substance issues across all substances, including tobacco. Participants were most likely to seek advice from senior colleagues in their practice.Early-career GPs reported lower than optimal levels of confidence for all substances. Our findings have important implications for educators globally. Education that improves confidence across all 5As for high-prevalence substances (tobacco and alcohol) while focusing on increasing comfort screening and improving understanding of referral pathway options for low-prevalence substances may improve early-career GPs' confidence. This could increase engagement in managing substance use issues potentially leading to better health and wellbeing outcomes for patients.

FREE-FLAP MONITORING: REVIEW AND CLINICAL APPROACH.

Microvascular free flap reconstruction is a routine option for coverage of a variety of tissue defects. Accurate monitoring in the postoperative period is a crucial part of successful flap surgery allowing early detection of vascular compromise and prompt intervention in flap salvaging. Despite that many safety procedures to assess flap viability have been developed, flap failure is consistently seen in 2-5% of free tissue transfers. In addition, great progress is being made in relation to various state-of-the-art technologies for flap monitoring. However, the gold standard still remains clinical monitoring at most institutions even though there is no standardized management protocol. The review should present a prospective optimal monitoring protocol and introduce some of the latest monitoring devices based on the recent literature and personal experience.

Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer.

OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry. Functional and preclinical experiments, as well as expression analysis of stromal markers and gemcitabine metabolism pathways were performed in murine and human specimen to investigate the preclinical implications and the mechanism of gemcitabine accumulation. RESULTS: Gemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2',2'-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5'-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%. CONCLUSIONS: Our findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.

Fasciitis necrotisans - duplicitas casuum.

Necrotizing fasciitis is a dangerous bacterial infectious disease that is not commonplace in Czech society. On the other hand, neither is it so rare that the majority of surgeons should not come across it occasionally. In the early stages, pathological changes in fascia, subcutaneous tissue and even skin may run an inconspicuous course. However, this can rapidly deteriorate into shock and sepsis which may lead to multi-organ failure and an imminent life-threatening condition. The fatality rate of necrotizing fasciitis among high-risk groups (e.g. diabetics, patients who are immuno-compromised, obese and/or elderly, malnourished, or with a history of drug use), is particularly steep, reaching as high as 73%. Treatment for this condition consists of early, radical surgical intervention in conjunction with targeted antibiotherapy. Complex resuscitative and intensive care, including rehabilitation, are standard components of post-surgical management. Use of hyperbaric oxygen therapy, if such an opportunity exists, is also recommended. Interdisciplinary collaboration is a vital prerequisite for successful treatment. This article describes two case-studies of necrotizing fasciitis that occurred in men of similar age during a three-year period. Both patients presented with very similar and complicated disease courses, and both were successfully treated by the same interdisciplinary team comprised of clinicians from various specialized departments. Key words: necrotizing fasciitis - radical necrectomy - antibiotherapy - hyperbaric oxygen therapy - complex resuscitative and intensive care.

Staging and surgical approaches in gastric cancer: a clinical practice guideline.

BACKGROUND: Resection is the cornerstone of cure for gastric adenocarcinoma; however, several aspects of surgical intervention remain controversial or are suboptimally applied at a population level, including staging, extent of lymphadenectomy (lnd), minimum number of lymph nodes that have to be assessed, gross resection margins, use of minimally invasive surgery, and relationship of surgical volumes with patient outcomes and resection in stage iv gastric cancer. METHODS: Literature searches were conducted in databases including medline (up to 10 June 2016), embase (up to week 24 of 2016), the Cochrane Library and various other practice guideline sites and guideline developer Web sites. A practice guideline was developed. RESULTS: One guideline, seven systematic reviews, and forty-eight primary studies were included in the evidence base for this guidance document. Seven recommendations are presented. CONCLUSIONS: All patients should be discussed at a multidisciplinary team meeting, and computed tomography (ct) imaging of chest and abdomen should always be performed when staging patients. Diagnostic laparoscopy is useful in the determination of M1 disease not visible on ct images. A D2 lnd is preferred for curative-intent resection of gastric cancer. At least 16 lymph nodes should be assessed for adequate staging of curative-resected gastric cancer. Gastric cancer surgery should aim to achieve an R0 resection margin. In the metastatic setting, surgery should be considered only for palliation of symptoms. Patients should be referred to higher-volume centres and those that have adequate support to manage potential complications. Laparoscopic resections should be performed to the same standards as those for open resections, by surgeons who are experienced in both advanced laparoscopic surgery and gastric cancer management.

The ROARI project - Road Accident Acute Rehabilitation Initiative: a randomised clinical trial of two targeted early interventions for road-related trauma.

OBJECTIVES: To determine the effectiveness of an Early Rehabilitation Intervention (ERI ) versus a Brief Education Intervention (BEI) following road trauma. PRIMARY OBJECTIVE: return to work or usual activities at 12 weeks (for minor/moderate injury) and 24 weeks for major injury. SECONDARY OBJECTIVES: Reduction in pain, anxiety, depression, disability and incidence of Post Traumatic Stress Disorder and improved quality of life. DESIGN: A multi-site single-blinded stratified randomized clinical trial (RCT). METHODS: 184 patients (92 in each arm) were recruited over 18 months and followed for 12 weeks (minor/moderate injury) and 24 weeks (major injury). Screening questionnaires at 2-4 weeks and follow-up interviews by phone for all outcome measures were undertaken. For those in the ERI group with a positive screen for high risk of persistent symptoms, an early assessment and intervention by a Rehabilitation Physician was offered. Those in the BEI group were sent written information and advised to see their GP. RESULTS: 89.4% of injuries were mild in this cohort. At 12 weeks 73.8% and 69.1% of patients in the ERI and the BEI groups respectively had returned to work or usual activities. There were no significant differences between the two intervention groups with respect to the primary or any secondary outcome measures. CONCLUSION: This is the first RCT of an ERI following road trauma in Australia. A targeted ERI is as effective as a BEI in assisting those with mild/moderate trauma to return to work or usual activities.

A Comparison of the Status, Legal, Economic, and Psychological Characteristics of Types of Adult Male Gamblers.

Gambling behavior is not a unique behavior. There are certain differences in behavior, gambling habits, gambling beliefs, and their reflection in psychosocial life. We have compared three groups of adult male gamblers­sports gamblers (n = 41), machine gamblers (n = 36), and poker gamblers (n = 35)­in regard to measures of personal status and legal-social characteristics. We found no difference between groups in terms of the length of gambling behavior, personal status, or age. We found no legal difference between groups in terms of the number of court cases for debt, stealing, or family court cases. In terms of economic circumstances, sports gamblers suffered more losses than the other groups (p < 0.0001). There were higher rates of bankruptcy among sports gamblers compared with machine gamblers (p < 0.01). Sports gamblers were more likely to borrow money from the black market compared with the other groups (p < 0.01). In terms of mental health, sports and machine gamblers had more suicidal thoughts and gestures than poker gamblers (p < 0.05), whereas the rate of suicide attempts was higher in machine gamblers compared with poker players (p < 0.05). Our results indicated higher vulnerability in sports gamblers in terms of economic problems compared with the other groups, whereas machine gamblers had vulnerability to suicidal thoughts and suicidal attempts compared with poker gamblers.

[Optimizing the treatment procedure in crural ulcers - a pilot study of the surgical method]. / Optimalizace lécebného postupu u kozního trofického defektu bérce pilotní studie chirurgické metody.

INTRODUCTION: Current medical knowledge has provided us with a wide range of possibilities of treating chronic wounds. Over the recent decades, in particular, significant progress has been made in this field. The authors present an overview of current knowledge of chronic wound healing, pointing out the surgeons role in the process of chronic wound management. Using surgical therapy, we are able to heal a chronic wound in a shorter period of time, particularly if the treatment is accelerated by the application of platelet-rich plasma (PRP) as a source of growth factors. METHODS: The pilot randomized prospective study included four patients with chronic wounds of the lower leg after previous failure of conservative therapy who were indicated for skin transplantation. Following previous vacuum-assisted closure therapy, the patients undergoing skin transplantation were prospectively randomized into two groups. Autologous PRP was used in one of the groups and standard skin transplantation without PRP was performed in the other one. RESULTS: In the PRP group, 99% of the wound areas were healed on the 15th day after the operation. In the other group, 90% of the areas were healed on the 15th day following the operation. In the PRP group, complete healing of the defect occurred in both patients at 15 and 20 days post-surgery. In the second group, one patient completely healed within 28 days; the other one was not fully healed even at 3 months post-surgery. CONCLUSIONS: Most patient groups at great risk may benefit from the method using PRP, as well as patients with chronic wounds who have failed conventional methods available for both general and local therapy. This fact has been confirmed by the authors initial experience presented.Key words: platelet-rich plasma (PRP) - platelets wound healing chronic wound.

Trauma- and Violence-Informed Empowering Care for Sexual Assault Survivors.

BACKGROUND: Forensic nurse examiners, including sexual assault nurse examiners, provide care for survivors holistically through healthcare, emotional support, connection to follow-up care, safety planning, and, if desired, evidence collection to aid in the prosecution of sexual assault. There is increasing recognition that trauma-informed care must also include an understanding of the impacts of structural violence on minoritized patients to ensure health equity. AIM: To help address this guidance gap, we expanded Campbell and colleagues' empowering care model using a trauma- and violence-informed care (TVIC) lens. METHODS: We used an iterative discussion-based process that included five joint meetings between a seven-member transdisciplinary research team and a five-member nurse advisory board. RESULTS: In a TVIC-informed empowering care model, we propose behavioral examples for forensic nurses for each of Campbell et al.'s five key domains of empowering care for forensic nurse examinations (i.e., build rapport and establish trust, show compassion, provide patient-directed care, convey professionalism, and provide resource referral and follow-up). CONCLUSIONS: These behavioral examples for nurses can help guide forensic nurse training and practice to reduce disparities in treatment and follow-up support. Structures and systems are needed that enable forensic nurses to provide trauma- and violence-informed empowering care to survivors of sexual assault and, over time, increase the accessibility of forensic nurse examinations and improve patient outcomes.

Marine mammals as indicators of Anthropocene Ocean Health.

The current state of marine mammal populations reflects increasing anthropogenic impacts on the global Ocean. Adopting a holistic approach towards marine mammal health, incorporating healthy individuals and healthy populations, these taxa present indicators of the health of the overall Ocean system. Their present deterioration at the animal, population and ecosystem level has implications for human health and the global system. In the Anthropocene, multiple planetary boundaries have already been exceeded, and quiet tipping points in the Ocean may present further uncertainties. Long and short-term monitoring of marine mammal health in the holistic sense is urgently required to assist in evaluating and reversing the impact on Ocean Health and aid in climate change mitigation.

Alcohol's Role in Campus Sexual Assault Bystander Behavior: A Systematic Review.

Between 50% and 70% of campus sexual assaults (SA) involve alcohol and campuses frequently promote bystander intervention strategies to prevent SA in student party contexts. This systematic review evaluates the measurement and outcomes of quantitative studies on how alcohol affects campus SA bystander outcomes. Using four search strategies and rigorous systematic review methods, we conducted a review of 36 studies. We included studies published after 2,000 conducted with college students in the United States, its territories, and Canada which contained information on alcohol use and SA bystander outcomes (behaviors and upstream proxies). Only a third of included studies measured bystander behavior directly, the majority measured upstream proxies (e.g., intentions, self-efficacy). Most studies considered the influence of victim intoxication on bystander outcomes. No studies assessed the pharmacological or physiological effects of alcohol on bystander outcomes. A single study examined hypothetical bystander responses when intoxicated, one-third examined bystander's typical alcohol use in relation to bystander outcomes. Many findings are contradictory, including fundamental details such as how often students encounter SA involving alcohol or whether bystanders' alcohol use predicts outcomes. Findings suggest that students are less likely help intoxicated victims compared to sober victims, but there are clear moderating factors. Perpetrator intoxication was not studied in relation to bystander behavior and did not influence any upstream proxies. Evaluations of interventions on alcohol and bystander topics are promising yet more research is required. This review illuminates key gaps in the literature, including the need for validated measures and scenarios, event-level studies, and alcohol administration trials.

Sexual and Relationship Violence Among LGBTQ+ College Students: A Scoping Review.

Although there has been increased attention to campus sexual and relationship violence (SRV) because of Title IX and the #MeToo movement, much of that attention has focused on victimization of cisgender heterosexual women. This scoping review uncovers information from empirical studies on what is known about LGBTQ+ (e.g., lesbian, gay, bisexual, transgender, queer, and nonbinary) students' experiences of campus SRV. Using rigorous scoping review methods (i.e., searches of 15 databases, searches of expert websites, hand searching, reference harvesting, and forward citation chaining), we identified 60 documents published since 2000 that contained findings from empirical studies related to LGBTQ+ students and SRV on U.S. college and university campuses. Through content analysis, we summarized findings around five key themes: (1) extent and types of victimization, (2) negative outcomes, (3) knowledge of and attitudes about SRV, (4) perspectives on SRV services and prevention education programs, and (5) recommendations from study authors based on their findings. Implications for research, practice, and policy based on these findings are discussed.

LGBTQ+-Affirming Campus Sexual and Relationship Violence Prevention: A Qualitative Study.

LGBTQ+ (e.g., lesbian, gay, bisexual, transgender, nonbinary, queer) people are often left out of campus sexual and relationship violence (SRV) prevention efforts despite experiencing higher rates of SRV. To inform LGBTQ+-affirming prevention efforts, we use a practice-to-research approach to aggregate wisdom from 32 LGBTQ+ professionals working to address campus SRV among LGBTQ+ college students garnered through semi-structured interviews. Participants shared four approaches to including or excluding LGBTQ+ students in campus SRV prevention programs as well as recommendations to cultivate more LGBTQ+-affirming campus SRV prevention efforts. We summarize recommendations for possible action steps at individual, relationship, community, and policy levels of the social ecological model for LGBTQ+-affirming campus SRV prevention.

Campus interpersonal violence survivor advocacy services.

Objective: Although there has been increased attention to campus interpersonal violence, there is limited information on survivor advocacy services. Participants: We recruited participants from 155 U.S. institutions of higher education responsible for advocacy services on their campus. Methods: We used a community participatory action approach in partnership with the Campus Advocacy and Prevention Professionals Association to develop and disseminate a survey regarding campus advocacy services. Results: Participants shared critical insights about (a) advocacy staffing/caseload, (b) program structure, (c) advocacy practices, and (d) connection to services for people who had caused harm. We found that advocacy programs are often providing best practice services for survivors of violence but operating with few staff and unclear privacy protections. Conclusions: This study provided crucial preliminary information about how campuses provide advocacy services, but more researcher-practitioner engagement is needed to build on this study and establish clear practice guidelines.

A Scoping Review of Human Trafficking Screening and Response.

Service providers are increasingly asked to identify individuals who are experiencing trafficking and to connect them with resources and support. Nonetheless, identification is complicated by the reality that those who are experiencing trafficking may rarely self-identify, and providers may fail to identify individuals who are experiencing trafficking due to lack of guidance on how to screen for trafficking capably and sensitively. With the aim of guiding practice, we undertook a scoping review to search for and synthesize trafficking screening tools and response protocols. Following the PRISMA extension for Scoping Reviews (PRISMA-ScR), we located 22 screening tools contained in 26 sources. We included any documents that described or tested human trafficking screening tools, screening or identification protocols, response protocols, or guidelines that were published in any year. All documents were abstracted using a standardized form. Key findings showed that most tools were developed by practice-based and non-governmental organizations located in the U.S. and were administered in the U.S. Few screening tools have been rigorously evaluated. The common types of screening questions and prompts included (a) work conditions; (b) living conditions; (c) physical health; (d) travel, immigration, and movement; (e) appearance and presentation; (f) mental health, trauma, and substance abuse; (g) associations and possessions; and (h) arrests and prior involvement with law enforcement. We were not able to locate specific response protocols that provided step-by-step guidance. Nonetheless, the review revealed available practice-based and research-based evidence to help inform guidance concerning how screening and identification of human trafficking may be administered.

ABHD6 suppression promotes anti-inflammatory polarization of adipose tissue macrophages via 2-monoacylglycerol/PPAR signaling in obese mice.

OBJECTIVE: Pro-inflammatory polarization of adipose tissue macrophages (ATMs) plays a critical role in the pathogenesis of obesity-associated chronic inflammation. However, little is known about the role of lipids in the regulation of ATMs polarity and inflammation in response to metabolic stress. Deletion of α/ß-hydrolase domain-containing 6 (ABHD6), a monoacylglycerol (MAG) hydrolase, has been shown to protect against diet-induced obesity and insulin resistance. METHODS: Here we investigated the immunometabolic role of macrophage ABHD6 in response to nutrient excess using whole-body ABHD6-KO mice and human and murine macrophage cell-lines treated with KT203, a selective and potent pharmacological ABHD6 inhibitor. RESULTS: KO mice on high-fat diet showed lower susceptibility to systemic diet-induced inflammation. Moreover, in the setting of overnutrition, stromal vascular cells from gonadal fat of KO vs. control mice contained lower number of M1 macrophages and exhibited enhanced levels of metabolically activated macrophages (MMe) and M2 markers, oxygen consumption, and interleukin-6 (IL-6) release. Likewise, under in vitro nutri-stress condition, inhibition of ABHD6 in MMe-polarized macrophages attenuated the expression and release of pro-inflammatory cytokines and M1 markers and induced the upregulation of lipid metabolism genes. ABHD6-inhibited MMe macrophages showed elevated levels of peroxisome proliferator-activated receptors (PPARs) and 2-MAG species. Notably, among different MAG species, only 2-MAG treatment led to increased levels of PPAR target genes in MMe macrophages. CONCLUSIONS: Collectively, our findings identify ABHD6 as a key component of pro-inflammatory macrophage activation in response to excess nutrition and implicate an endogenous macrophage lipolysis/ABHD6/2-MAG/PPARs cascade, as a lipid signaling and immunometabolic pathway, which favors the anti-inflammatory polarization of ATMs in obesity.