Regulation of STAT1 and STAT4 Expression by Growth Factor and Interferon Supplementation in Sjögren's Syndrome Cell Culture Models.

Our goal was to investigate the effects of epidermal growth factor (EGF) and interferons (IFNs) on signal transducer and activator of transcription STAT1 and STAT4 mRNA and active phosphorylated protein expression in Sjögren's syndrome cell culture models. iSGECs (immortalized salivary gland epithelial cells) and A253 cells were treated with EGF, IFN-alpha, -beta, -gamma, or mitogen-activated protein kinase p38 alpha (p38-MAPK) inhibitor for 0-24-48-72 h. STAT1 and STAT4 mRNA expression was quantified by qRT-PCR. Untreated and treated cells were compared using the delta-delta-CT method based on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) normalized relative fold changes. phospho-tyrosine-701-STAT1 and phospho-serine-721-STAT4 were detected by Western blot analysis. STAT4 mRNA expression decreased 48 h after EGF treatment in A253 cells, immortalized salivary gland epithelial cells iSGECs nSS2 (sicca patient origin), and iSGECs pSS1 (anti-SSA negative Sjögren's Syndrome patient origin). EGF and p38-MAPK inhibitor decreased A253 STAT4 mRNA levels. EGF combined with IFN-gamma increased phospho-STAT4 and phospho-STAT1 after 72 h in all cell lines, suggesting additive effects for phospho-STAT4 and a major effect from IFN-gamma for phospho-STAT1. pSS1 and nSS2 cells responded differently to type I and type II interferons, confirming unique functional characteristics between iSGEC cell lines. EGF/Interferon related pathways might be targeted to regulate STAT1 and STAT4 expression in salivary gland epithelial cells. Further investigation is required learn how to better target the Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT) pathway-mediated inflammatory response in Sjögren's syndrome.

Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women : Postintervention Follow-up of a Randomized Clinical Trial.

BACKGROUND: Although calcium and vitamin D (CaD) supplementation may affect chronic disease in older women, evidence of long-term effects on health outcomes is limited. OBJECTIVE: To evaluate long-term health outcomes among postmenopausal women in the Women's Health Initiative CaD trial. DESIGN: Post hoc analysis of long-term postintervention follow-up of the 7-year randomized intervention trial of CaD. (ClinicalTrials.gov: NCT00000611). SETTING: A multicenter (n = 40) trial across the United States. PARTICIPANTS: 36 282 postmenopausal women with no history of breast or colorectal cancer. INTERVENTION: Random 1:1 assignment to 1000 mg of calcium carbonate (400 mg of elemental calcium) with 400 IU of vitamin D3 daily or placebo. MEASUREMENTS: Incidence of colorectal, invasive breast, and total cancer; disease-specific and all-cause mortality; total cardiovascular disease (CVD); and hip fracture by randomization assignment (through December 2020). Analyses were stratified on personal supplement use. RESULTS: For women randomly assigned to CaD versus placebo, a 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years (1817 vs. 1943 deaths; hazard ratio [HR], 0.93 [95% CI, 0.87 to 0.99]), along with a 6% increase in CVD mortality (2621 vs. 2420 deaths; HR, 1.06 [CI, 1.01 to 1.12]). There was no overall effect on other measures, including all-cause mortality (7834 vs. 7748 deaths; HR, 1.00 [CI, 0.97 to 1.03]). Estimates for cancer incidence varied widely when stratified by whether participants reported supplement use before randomization, whereas estimates on mortality did not vary, except for CVD mortality. LIMITATION: Hip fracture and CVD outcomes were available on only a subset of participants, and effects of calcium versus vitamin D versus joint supplementation could not be disentangled. CONCLUSION: Calcium and vitamin D supplements seemed to reduce cancer mortality and increase CVD mortality after more than 20 years of follow-up among postmenopausal women, with no effect on all-cause mortality. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Engagement in Integrative and Nonpharmacologic Pain Management Modalities Among Adults with Chronic Pain: Analysis of the 2019 National Health Interview Survey.

Objective: To examine variables associated with engagement in (1) integrative health and medicine (IHM) and (2) nonpharmacologic modalities rather than opioids among United States adults with chronic pain. Methods: Using the 2019 National Health Interview Survey, we examined sociodemographic, pain, and mental health predictors of (1) the sum of IHM modalities (ie, chiropractic care, yoga/Tai Chi, massage, or meditation/guided imagery) used to manage pain and (2) exclusive engagement in nonpharmacologic pain management modalities (ie, IHM, a chronic pain self-management program, support groups, or physical, rehabilitative, occupational, or talk therapy) or opioids in the past 3 months. Results: Metropolitan residency, higher family income, higher education levels, increased number of pain locations, and increased frequency of pain limiting life/work activities were associated with increased odds of IHM engagement. Older age, male sex, non-Hispanic Black/African American race/ethnicity, and daily opioid use were associated with decreased odds of IHM engagement. Older age, male sex, and increased depressive symptoms were associated with decreases in the count of IHM modalities used to manage pain. Metropolitan residency, higher family income, and higher education levels were associated with increased odds of exclusive nonpharmacologic modality engagement. Older age and increasing frequency of pain limiting life/work activities were associated with decreased odds of exclusive nonpharmacologic modality engagement. Conclusions: We identified several contrasts between factors prevalent among individuals with chronic pain and factors associated with engagement in nonpharmacologic and IHM modalities. These results support efforts to address barriers to accessing these modalities among subpopulations of adults with chronic pain (eg, older adults, individuals identifying as Black/African American, rural residents, and those with lower levels of education and income).

Development and validation of a model to predict acute kidney injury following high-dose methotrexate in patients with lymphoma.

STUDY OBJECTIVE: To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure. DESIGN: Retrospective analysis. SETTING: Multisite integrated health system throughout Minnesota and Wisconsin. PATIENTS: Adult patients with lymphoma who received HDMTX as a 4-h infusion. MEASUREMENTS AND MAIN RESULTS: LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort. CONCLUSION: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

Systemic ciprofloxacin treatment of multidrug-resistant Aggregatibacter actinomycetemcomitans in severe periodontitis.

An adult periodontitis patient treated with mechanical/surgical therapy experienced gingival necrosis and granulomas post-treatment. Aggregatibacter actinomycetemcomitans, a tissue-invasive pathogen, was recovered and multidrug-resistant but susceptible to ciprofloxacin. Systemic ciprofloxacin eliminated A. actinomycetemcomitans with marked clinical improvement. Ciprofloxacin may be prescribed for A. actinomycetemcomitans periodontal infection unresponsive to the common amoxicillin-metronidazole treatment.

Anti-Inflammatory Effects of Bioactive Compounds from Seaweeds, Bryozoans, Jellyfish, Shellfish and Peanut Worms.

Inflammation is a defense mechanism of the body in response to harmful stimuli such as pathogens, damaged cells, toxic compounds or radiation. However, chronic inflammation plays an important role in the pathogenesis of a variety of diseases. Multiple anti-inflammatory drugs are currently available for the treatment of inflammation, but all exhibit less efficacy. This drives the search for new anti-inflammatory compounds focusing on natural resources. Marine organisms produce a broad spectrum of bioactive compounds with anti-inflammatory activities. Several are considered as lead compounds for development into drugs. Anti-inflammatory compounds have been extracted from algae, corals, seaweeds and other marine organisms. We previously reviewed anti-inflammatory compounds, as well as crude extracts isolated from echinoderms such as sea cucumbers, sea urchins and starfish. In the present review, we evaluate the anti-inflammatory effects of compounds from other marine organisms, including macroalgae (seaweeds), marine angiosperms (seagrasses), medusozoa (jellyfish), bryozoans (moss animals), mollusks (shellfish) and peanut worms. We also present a review of the molecular mechanisms of the anti-inflammatory activity of these compounds. Our objective in this review is to provide an overview of the current state of research on anti-inflammatory compounds from marine sources and the prospects for their translation into novel anti-inflammatory drugs.

Efficacy of water application of a humic substance, butyric acid, vitamins C, D, and E and/or electrolytes on performance and mortality in health-challenged nursery pigs¹.

Health challenges continue to be rampant in nursery pigs which has led to increased industry-wide mortality trends. Therefore, the objective of these three studies was to evaluate a water supplement (HV; HydraVantage, Kent Nutrition Group, Muscatine, IA) which is a proprietary blend of a humic substance, butyric acid, and vitamins C, D, and E, as well as an electrolyte blend on nursery pig performance and mortality. Experiment 1 consisted of 196 crossbred weanling pigs (7 pigs per pen with 14 pens per treatment) which were randomly allotted by BW to two treatments consisting of control (water for 33 d) or HV at 15 g/L of stock solution and proportioned through a medicator (1:128) for 11 d followed by water for 22 d. There were no performance differences. However, mortality was reduced (P < 0.01) from 6.12% for the control to 0.00% for HV. In experiment 2, there were 488 weanling pigs (6 to 10 pigs/pen with 14 pens per treatment) which were randomly allotted by BW to four treatments in a 34-d trial. Treatment 1 was control (water), and treatments 2 and 4 were HV at 15 g/L of stock solution for 11 and 34 d, respectively. Treatment 3 utilized HV at 15 g/L stock solution during days 0 to 11 with 7.5 g HV/L stock solution utilized during days 11 to 21 followed by water. No performance differences were observed among the four treatments. Mortality was 10.89%, 4.82%, 5.54%, and 7.26% for treatments 1 to 4, respectively, with treatment 1 having a higher mortality (P < 0.05) compared to treatments 2 to 4. In experiment 3, a 2 × 2 factorial study was conducted (7 pigs per pen with 14 pens per treatment) in which the treatments were: 1) water; 2) HV at 15 g/L stock solution for 34 d; 3) electrolytes at 241 g/L stock solution for 34 d; and 4) HV at 15 g/L of stock solution and electrolytes at 226 g/L of stock for 34 d. Overall pen gain tended to be improved (P = 0.09) with supplemental HV. Moreover, mortality was reduced (P = 0.06) by 36% (16.86% mortality for treatments 1 and 3 vs. 10.73% mortality for treatments 2 and 4). Supplemental electrolytes had no effect on mortality. These data suggest that HV has a positive effect by reducing mortality in nursery pigs undergoing health challenges.

Hi-fun among men who have sex with men in Bangkok: A scoping study exploring key informants' perspectives on hi-fun contexts, harms and support strategies.

The use of specific drugs (e.g. methamphetamine, GHB/GBL and other stimulants) to enhance sex among men who have sex with men (MSM), is the focus of global public health concern because of links to social harms, poor mental and sexual health. Often called 'chemsex' in Western settings or 'hi-fun' in Southeast Asia, this type of sexualised drug use is increasingly visible in Thailand where the unique sociocultural and legislative environments shape sexual cultures and harms. This study aimed to develop an understanding of key informants' perspectives on hi-fun contexts, harms and current responses in Bangkok. In-depth interviews were conducted with thirteen key informants from clinical, community, policy and development organisations. Four key informants had personal experience of hi-fun. Interviews covered hi-fun contexts, harms and support, were transcribed verbatim, translated to English (where necessary) and analysed using a thematic framework. MSM hi-fun 'influencers' shape norms and provide support online, primarily through Twitter. Hi-fun was linked to Westernisation and wealth; complex hierarchies emerged from asymmetries in social/financial capital. Police coercion towards MSM engaged in hi-fun was a concern. Given the nature of their funding, HIV/HCV/STI transmission was the most pressing focus for many organisations, however key informants were concerned especially about drug overdoses and mental health/well-being impacts. The political and economic context means funding for MSM health in Thailand focuses primarily on HIV prevention/treatment; restrictions on development aid constrain holistic hi-fun focused service development. Most hi-fun support was informally developed; successful strategies relied on partnership working and peer developed/delivered services, some of which were adapted from high-income settings. Despite substantial barriers, organisations developed services responding to the needs of MSM engaged in hi-fun. Given that many were informally developed or adapted from high-income settings, establishing a theoretical basis for further interventions that is grounded in this unique context is a priority.

New therapeutic strategies for Mycobacterium abscessus pulmonary diseases - untapping the mycolic acid pathway.

INTRODUCTION: Treatment options against Mycobacterium abscessus infections are very limited. New compounds are needed to cure M. abscessus pulmonary diseases. While the mycolic acid biosynthetic pathway has been largely exploited for the treatment of tuberculosis, this metabolic process has been overlooked in M. abscessus, although it offers many potential drug targets for the treatment of this opportunistic pathogen. AREAS COVERED: Herein, the authors review the role of the MmpL3 membrane protein and the enoyl-ACP reductase InhA involved in the transport and synthesis of mycolic acids, respectively. They discuss their importance as two major vulnerable drug targets in M. abscessus and report the activity of MmpL3 and InhA inhibitors. In particular, they focus on NITD-916, a direct InhA inhibitor against M. abscessus, particularly warranted in the context of multidrug resistance. EXPERT OPINION: There is an increasing body of evidence validating the mycolic acid pathway as an attractive drug target to be further exploited for M. abscessus lung disease treatments. The NITD-916 studies provide a proof-of-concept that direct inhibitors of InhA are efficient in vitro, in macrophages and in zebrafish. Future work is now required to improve the activity and pharmacological properties of these inhibitors and their evaluation in pre-clinical models.

UChicago Medicine Grows Through Partnership Synergies.

SUMMARY: University of Chicago Health System-UChicago Medicine-recently joined forces with AdventHealth's Great Lakes Region to expand access to services, treatment options, and clinical trials to residents in Chicago's western suburbs. Other organizations may want to follow that approach in developing and maintaining a high-quality and integrated healthcare ecosystem-one that not only increases access to care for underserved populations but also responds to changing consumer preferences and behavior. Building partnerships with other systems that possess similar values and complementary strengths is an effective way to provide patients with convenient, high-quality care closer to home. Early results of the joint venture show promising synergies and benefits.

Survey-based Evaluation of a Fish Consumption Information Dissemination Campaign Within an Integrated Health System: Learnings From ChooseYourFish.

INTRODUCTION/OBJECTIVES: Safe fish consumption is important for people who are or could become pregnant. A health system in Minnesota partnered with the Minnesota Department of Health to develop and disseminate messages to promote safe fish consumption for this population via the ChooseYourFish initiative. The ChooseYourFish message was delivered through 5 channels: the Healthy Pregnancy Program (HPP) with phone-based coaching, a clinic brochure, in the clinic after visit summary (AVS), direct mailing of the brochure with a letter, and in images on clinic waiting room monitors. METHODS: We designed a pragmatic evaluation to understand the likelihood that each channel would result in awareness of the message and increase a recipient's intent to act on the information. We surveyed 1050 women aged 18 to 40 in March-May 2020. Results are reported with descriptive statistics. RESULTS: The survey was completed by 524 respondents (51%). Respondents receiving the ChooseYourFish message through any channel except clinic monitors reported a higher awareness of recommendations about eating fish (42%-56%) than respondents in the no-message comparison group (21%). The after visit summary and Healthy Pregnancy Program channels had more confidence in following recommendations (50%-54%) and showed more intention to eat fish (61%-62%) compared to lower-intensity channels (24%-31% and 19%-32%, respectively). CONCLUSIONS: Messages delivered by an often-trusted source (eg, healthcare provider) were more likely to increase confidence and intent. Despite the trend toward online health information, physical brochures still have large reach. Repetition of exposure may be important. Because all communication channels have advantages and drawbacks, using multiple delivery channels is appropriate in communication campaigns.

Systematic Investigation of Tether Length and Phosphorus Configuration in Backbone Constrained Macrocyclic Nucleic Acids to Modulate Binding Kinetics for RNA.

We recently described a chemical strategy to pre-organize a trinucleotide subunit in a conformation suitable for Watson-Crick base pairing for modulating the binding kinetics of single-stranded oligonucleotides (ONs) using bis-phosphonate esters bridging hydrocarbon tethers to provide 11- and 15-membered macrocyclic analogues. In this manuscript, we describe the synthesis of all eight P-stereoisomers of macrocyclic 12-, 13-, 14-, and 16-membered hydrocarbon-bridged nucleotide trimers, their incorporation into ONs, and biophysical characterization of the modified ONs. The size of the macrocyclic tether and configuration at phosphorus had profound effects on hybridization kinetics. ONs containing 12- and 13-membered rings exhibited faster on-rates (up to 5-fold) and off-rates (up to 161-fold). In contrast, ONs using the larger ring size macrocycles generally exhibited smaller changes in binding kinetics relative to unmodified DNA. Interestingly, several of the analogues retained significant binding affinity for RNA based on their dissociation constants, despite being modestly destabilizing in the thermal denaturation experiments, highlighting the potential utility of measuring dissociation constants versus duplex thermal stability when evaluating novel nucleic acid analogues. Overall, our results provide additional insights into the ability of backbone-constrained macrocyclic nucleic acid analogues to modulate hybridization kinetics of modified ONs with RNA.

Combination Sodium Nitrite and Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity in a "2-Hit" Murine Model.

Background Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a "2-hit" murine model. Methods and Results Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat diet and N(ω)-nitro-L-arginine methyl ester (L-NAME) (0.5 g/L per day) via drinking water for 10 weeks. At week 5, mice were randomized into either vehicle (normal saline) or combination treatment with sodium nitrite (75 mg/L in the drinking water) and hydralazine (2.0 mg/kg IP, BID). Cardiac structure and function were monitored with echocardiography and invasive hemodynamic measurements. Cardiac mitochondrial respiration, aortic vascular function, and exercise performance were also evaluated. Circulating and myocardial nitrite were measured to determine the bioavailability of NO. Circulating markers of oxidative or nitrosative stress as well as systemic inflammation were also determined. Severe HFpEF was evident by significantly elevated E/E', LVEDP, and Tau in mice treated with L-NAME and HFD, which was associated with impaired NO bioavailability, mitochondrial respiration, aortic vascular function, and exercise capacity. Treatment with sodium nitrite and hydralazine restored NO bioavailability, reduced oxidative and nitrosative stress, preserved endothelial function and mitochondrial respiration, limited the fibrotic response, and improved exercise capacity, ultimately attenuating the severity of "two-hit" HFpEF. Conclusions Our data demonstrate that nitrite, a well-established biomarker of NO bioavailability and a physiological source of NO, is significantly reduced in the heart and circulation in the "2-hit" mouse HFpEF model. Furthermore, sodium nitrite+hydralazine combined therapy significantly attenuated the severity of HFpEF in the "2-hit" cardiometabolic HFpEF. These data suggest that supplementing NO-based therapeutics with a potent antioxidant and vasodilator agent may result in synergistic benefits for the treatment of HFpEF.

Integrated Care as a Model for Interprofessional Disease Management and the Benefits for People Living with HIV/AIDS.

INTRODUCTION: Today, antiretroviral therapy (ART) is effectively used as a lifelong therapy to treat people living with HIV (PLWH) to suppress viral replication. Moreover, PLWH need an adequate care strategy in an interprofessional, networked setting of health care professionals from different disciplines. HIV/AIDS poses challenges to both patients and health care professionals within the framework of care due to frequent visits to physicians, avoidable hospitalizations, comorbidities, complications, and the resulting polypharmacy. The concepts of integrated care (IC) represent sustainable approaches to solving the complex care situation of PLWH. AIMS: This study aimed to describe the national and international models of integrated care and their benefits regarding PLWH as complex, chronically ill patients in the health care system. METHODS: We conducted a narrative review of the current national and international innovative models and approaches to integrated care for people with HIV/AIDS. The literature search covered the period between March and November 2022 and was conducted in the databases Cinahl, Cochrane, and Pubmed. Quantitative and qualitative studies, meta-analyses, and reviews were included. RESULTS: The main findings are the benefits of integrated care (IC) as an interconnected, guideline- and pathway-based multiprofessional, multidisciplinary, patient-centered treatment for PLWH with complex chronic HIV/AIDS. This includes the evidence-based continuity of care with decreased hospitalization, reductions in costly and burdensome duplicate testing, and the saving of overall health care costs. Furthermore, it includes motivation for adherence, the prevention of HIV transmission through unrestricted access to ART, the reduction and timely treatment of comorbidities, the reduction of multimorbidity and polypharmacy, palliative care, and the treatment of chronic pain. IC is initiated, implemented, and financed by health policy in the form of integrated health care, managed care, case and care management, primary care, and general practitioner-centered concepts for the care of PLWH. Integrated care was originally founded in the United States of America. The complexity of HIV/AIDS intensifies as the disease progresses. CONCLUSIONS: Integrated care focuses on the holistic view of PLWH, considering medical, nursing, psychosocial, and psychiatric needs, as well as the various interactions among them. A comprehensive expansion of integrated care in primary health care settings will not only relieve the burden on hospitals but also significantly improve the patient situation and the outcome of treatment.

Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy.

BACKGROUND AND PURPOSE: Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy. MATERIALS AND METHODS: We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps. RESULTS: The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices. CONCLUSIONS: Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.

An experimental test of integrating imagery with approach bias modification for alcohol: A cautionary tale.

OBJECTIVES: In terms of dual process models, behaviour can be conceived of as the outcome of an interplay between reflective, top-down and impulsive, bottom-up processes. Behaviour change interventions may benefit from targeting both types of processes in a coherent way. One approach to this, in the context of reducing hazardous drinking, is to combine imagery involving real-life situations involving alcohol with the simple actions involved in Approach Bias Modification (ApBM), a form of Cognitive Bias Modification. DESIGN: We developed and tested a version of this Imagery-enhanced Approach Bias Modification (IApBM) in an experimental design, with two independent factors: imagery versus control and ApBM versus control training components (N = 139). METHODS: An effect of integrating the training factors was hypothesized on the alcohol-approach bias of an alcohol Approach-Avoidance Task. Further exploratory analyses were performed for the bias on alcohol-related Single Attribute Implicit Association Tests and on alcohol-related questionnaires. Finally, the psychometric properties of an imagery interference effect during training were explored. RESULTS: Results showed no benefit of the training and in fact suggested a negative interaction in which combining the training components appeared to block reductions in craving effected by each in isolation. The reliability of the imagery-related interference effect was high and the effect was correlated with alcohol-related scales. CONCLUSIONS: In conclusion, it appears that interference between training components decreases their individual effects when combining imagery and ApBM in the current way. The imagery-related interference effects that could be measured during training conditions may be useful as an implicit measure of automatic processes underlying hazardous drinking.

S-144 lack of association between glycated hemoglobin and adverse outcomes in diabetic patients undergoing ventral hernia repair: an ACHQC study.

INTRODUCTION: Elevated preoperative glycated hemoglobin (HbA1c) is believed to predict complications in diabetic patients undergoing ventral hernia repair (VHR). Our objective was to assess the association between HbA1c and outcomes of VHR in diabetic patients. METHODS: We conducted a retrospective cohort study using the Abdominal Core Health Quality Collaborative (ACHQC) database. We included adult diabetic patients who underwent elective VHR with an available HbA1c result. The patients were divided into two groups (HbA1c < 8% and HbA1c ≥ 8%). Patient demographics, comorbidities, hernia characteristics, operative details, and surgical outcomes were compared. Multivariable logistic regression analysis of complications was performed. Cox proportional hazard regression was used to assess probability of composite recurrence at different HbA1c levels. RESULTS: 2167 patients met the inclusion criteria (HbA1c < 8% = 1,776 and HbA1c ≥ 8% = 391). Median age was 61 years and median body mass index was 34 kg/m2. 75% had an American Society of Anesthesiology class of 3. The median HbA1c was 6.5% in the HbA1c < 8% group versus 8.7% in the HbA1c ≥ 8% group. 73% were incisional hernias, 34% were recurrent, and median hernia width was 6 cm. Open approach was used in 63% and myofascial release was performed in 46%. Median follow-up was 27 days. There were no clinically significant differences in the rates of overall 30-day complications, wound complications, reoperation, readmission, mortality, length of stay and quality of life and pain scores between the two groups. Regression analyses did not identify an association between HbA1c and the rates of complications, surgical site infection or composite recurrence across the spectrum of HbA1c values. CONCLUSION: Our study finds no evidence of an association between HbA1c and operative outcomes in diabetic patients undergoing elective VHR.

Natural source zone depletion (NSZD) insights from over 15 years of research and measurements: A multi-site study.

Site-average Natural Source Zone Depletion (NSZD) rates measured from 40 petroleum light non-aqueous phase liquid (LNAPL) source zone sites were compiled from researchers, project reports, and scientific papers. At each site, the following data were compiled: i) general site location; ii) LNAPL fuel type; iii) measurement method, number of locations, and number of measurements per location; and iv) calculated site-average NSZD rate in liters per hectare per year (L/ha/yr) per site and the associated measurement method (i.e., Gradient Method, Carbon Traps, Dynamic Closed Chamber (DCC), or Thermal Monitoring). The resulting dataset showed site-average NSZD rates that ranged from 650 to 152,000 L/ha/yr (70 to 16,250 gallons per acre per year (gal/acre/yr)), with a median value of 9,540 L/ha/yr (1,020 gal/acre/yr). The median site-average NSZD rate by type of fuel spill did not show a statistically significant difference between fuel types. When comparing the different NSZD measurement methods applied to the same sites, the site-average NSZD rates differed by up to 4.8 times (i.e., ratio of faster rate to slower rate), with a median difference of 2.1 times. No clear bias was observed between NSZD rate measurement methods. At four sites with calculations of NSZD rates by season, NSZD rates were typically higher during summer and fall compared to winter and spring. For these sites, Q10 values (a measure of the increase in NSZD rate associated with a 10 °C increase in temperature) ranged from 0.8 to 15.1, with a median of 2.2. The implications of this study suggest that increasing mean annual soil temperature at a site using engineered methods could potentially increase the biodegradation rate (e.g., an increase of 10 °C could double the NSZD rate). Finally, for five sites with site-average NSZD rates for multiple years, average NSZD rates varied by 1.1 to 4.9 times across years. Overall, the evaluation of NSZD rates measured at 40 LNAPL sites suggests that measurable NSZD occurs across a broad range of LNAPL sites. Although NSZD rates vary across sites, fuel type is not the primary factor explaining observed differences in rates.

Quantifying the contribution of triglycerides to metabolic resilience through the mixed meal model.

Despite the pivotal role played by elevated circulating triglyceride levels in the pathophysiology of cardio-metabolic diseases many of the indices used to quantify metabolic health focus on deviations in glucose and insulin alone. We present the Mixed Meal Model, a computational model describing the systemic interplay between triglycerides, free fatty acids, glucose, and insulin. We show that the Mixed Meal Model can capture deviations in the post-meal excursions of plasma glucose, insulin, and triglyceride that are indicative of features of metabolic resilience; quantifying insulin resistance and liver fat; validated by comparison to gold-standard measures. We also demonstrate that the Mixed Meal Model is generalizable, applying it to meals with diverse macro-nutrient compositions. In this way, by coupling triglycerides to the glucose-insulin system the Mixed Meal Model provides a more holistic assessment of metabolic resilience from meal response data, quantifying pre-clinical metabolic deteriorations that drive disease development in overweight and obesity.

Complex Mixture Analysis of Emerging Contaminants Generated from Coal Tar- and Petroleum-Derived Pavement Sealants: Molecular Compositions and Correlations with Toxicity Revealed by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

Pavement sealants are of environmental concern because of their complex petroleum-based chemistry and potential toxicity. Specifically, coal tar-derived sealants contain high concentrations of toxic/carcinogenic polycyclic aromatic hydrocarbons (PAHs) that, when weathered, can be transferred into the surrounding environment. Previous studies have demonstrated the effects of coal tar sealants on PAH concentration in nearby waterways and their harmful effects in aquatic ecosystems. Here, we investigate and compare the molecular composition of two different pavement sealants, petroleum asphalt- and coal tar-derived, and their photoproducts, by positive-ion (+) atmospheric pressure photoionization (APPI) and negative-ion (-) electrospray ionization (ESI) coupled with ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry to address species (high-boiling and/or high oxygen content) that lie outside the analytical window of other techniques due to ultra-high molecular complexity. In addition, we evaluate the toxicity of the water-soluble photoproducts by use of Microtox bioassay. The results demonstrate that the coal tar sealant contains higher amounts of PAHs and produces abundant water-soluble compounds, relative to unweathered materials, with a high abundance of PAH-like molecules of high toxicity. By comparison, the asphalt sealant produces fewer toxic water-soluble species, with molecular compositions that are consistent with natural dissolved organic matter. These results capture the mass, chemical diversity, toxicity, and source/photoproduct relationship of these compositionally complex emerging contaminants from the built environment.