TTLL12 has a potential oncogenic activity, suppression of ligation of nitrotyrosine to the C-terminus of detyrosinated α-tubulin, that can be overcome by molecules identified by screening a compound library.

Tubulin tyrosine ligase 12 (TTLL12) is a promising target for therapeutic intervention since it has been implicated in tumour progression, the innate immune response to viral infection, ciliogenesis and abnormal cell division. It is the most mysterious of a fourteen-member TTL/TTLL family, since, although it is the topmost conserved in evolution, it does not have predicted enzymatic activities. TTLL12 seems to act as a pseudo-enzyme that modulates various processes indirectly. Given the need to target its functions, we initially set out to identify a property of TTLL12 that could be used to develop a reliable high-throughput screening assay. We discovered that TTLL12 suppresses the cell toxicity of nitrotyrosine (3-nitrotyrosine) and its ligation to the C-terminus of detyrosinated α-tubulin (abbreviated to ligated-nitrotyrosine). Nitrotyrosine is produced by oxidative stress and is associated with cancer progression. Ligation of nitrotyrosine has been postulated to be a check-point induced by excessive cell stress. We found that the cytotoxicities of nitrotyrosine and tubulin poisons are independent of one another, suggesting that drugs that increase nitrotyrosination could be complementary to current tubulin-directed therapeutics. TTLL12 suppression of nitrotyrosination of α-tubulin was used to develop a robust cell-based ELISA assay that detects increased nitrotyrosination in cells that overexpress TTLL12 We adapted it to a high throughput format and used it to screen a 10,000 molecule World Biological Diversity SETTM collection of low-molecular weight molecules. Two molecules were identified that robustly activate nitrotyrosine ligation at 1 µM concentration. This is the pioneer screen for molecules that modulate nitrotyrosination of α-tubulin. The molecules from the screen will be useful for the study of TTLL12, as well as leads for the development of drugs to treat cancer and other pathologies that involve nitrotyrosination.

Natural Language Processing for Large-Scale Analysis of Eczema and Psoriasis Social Media Comments.

Social media tools are widely used by dermatologic patients. Eczema and psoriasis, two of the most common inflammatory skin diseases, are well-represented on the social media site Reddit. We used natural language processing tools to examine comments in subreddits r/psoriasis and r/eczema (combined user base >187,000), tracking commenters' interest levels and sentiments related to common treatments for psoriasis and eczema as well as discussions of adverse drug reactions. All comments from 2014-2020 from the subreddits r/eczema (n = 196,571) and r/psoriasis (n = 123,144) were retrieved and processed using natural language processing tools. Comment volume in r/eczema related to antibacterial therapies, lifestyle changes, and prednisone decreased from 2014-2020, whereas phototherapy comments remained stable, and dupilumab comment volume increased. Comment volume in r/psoriasis for newer therapeutics (including biologics and apremilast) increased after Food and Drug Administration approval, whereas older therapies such as etanercept, adalimumab, and methotrexate decreased over time. Sentiment scores tended to decrease in the years after Food and Drug Administration approval. Among psoriasis treatments, calcipotriene and branded calcipotriene/betamethasone foam had the highest sentiment, whereas apremilast had the lowest overall sentiment score. These analyses also identified changes in patient interest levels and sentiment related to eczema and psoriasis treatments, suggesting an area for additional research.

Multi-omics analyses of airway host-microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions.

The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe-host interactions in COPD through an in-depth profiling of the sputum metagenome, metabolome, host transcriptome and proteome from 99 patients with COPD and 36 healthy individuals in China. Multi-omics data were integrated using sequential mediation analysis, to assess in silico associations of the microbiome with two primary COPD inflammatory endotypes, neutrophilic or eosinophilic inflammation, mediated through microbial metabolic interaction with host gene expression. Hypotheses of microbiome-metabolite-host interaction were identified by leveraging microbial genetic information and established metabolite-human gene pairs. A prominent hypothesis for neutrophil-predominant COPD was altered tryptophan metabolism in airway lactobacilli associated with reduced indole-3-acetic acid (IAA), which was in turn linked to perturbed host interleukin-22 signalling and epithelial cell apoptosis pathways. In vivo and in vitro studies showed that airway microbiome-derived IAA mitigates neutrophilic inflammation, apoptosis, emphysema and lung function decline, via macrophage-epithelial cell cross-talk mediated by interleukin-22. Intranasal inoculation of two airway lactobacilli restored IAA and recapitulated its protective effects in mice. These findings provide the rationale for therapeutically targeting microbe-host interaction in COPD.

Variation in Survival and Gut Microbiome Composition of Hatchery-Grown Native Oysters at Various Locations within the Puget Sound.

The Olympia oyster (Ostrea lurida) of the Puget Sound suffered a dramatic population crash, but restoration efforts hope to revive this native species. One overlooked variable in the process of assessing ecosystem health is association of bacteria with marine organisms and the environments they occupy. Oyster microbiomes are known to differ significantly between species, tissue type, and the habitat in which they are found. The goals of this study were to determine the impact of field site and habitat on the oyster microbiome and to identify core oyster-associated bacteria in the Puget Sound. Olympia oysters from one parental family were deployed at four sites in the Puget Sound both inside and outside of eelgrass (Zostera marina) beds. Using 16S rRNA gene amplicon sequencing of the oyster gut, shell, and surrounding seawater and sediment, we demonstrate that gut-associated bacteria are distinct from the surrounding environment and vary by field site. Furthermore, regional differences in the gut microbiota are associated with the survival rates of oysters at each site after 2 months of field exposure. However, habitat type had no influence on microbiome diversity. Further work is needed to identify the specific bacterial dynamics that are associated with oyster physiology and survival rates. IMPORTANCE This is the first exploration of the microbial colonizers of the Olympia oyster, a native oyster species to the West Coast, which is a focus of restoration efforts. The patterns of differential microbial colonization by location reveal microscale characteristics of potential restoration sites which are not typically considered. These microbial dynamics can provide a more holistic perspective on the factors that may influence oyster performance.

Two mental models of integrated care for advanced liver disease: qualitative study of multidisciplinary health professionals.

OBJECTIVES: The purpose of this paper is to present two divergent mental models of integrated advanced liver disease (AdvLD) care among 26 providers who treat patients with AdvLD. SETTING: 3 geographically dispersed United States Veterans Health Administration health systems. PARTICIPANTS: 26 professionals (20 women and 6 men) participated, including 9 (34.6%) gastroenterology, hepatology, and transplant physicians, 2 (7.7%) physician assistants, 7 (27%) nurses and nurse practitioners, 3 (11.5%) social workers and psychologists, 4 (15.4%) palliative care providers and 1 (3.8%) pharmacist. MAIN OUTCOME MEASURES: We conducted qualitative in-depth interviews of providers caring for patients with AdvLD. We used framework analysis to identify two divergent mental models of integrated AdvLD care. These models vary in timing of initiating various constituents of care, philosophy of integration, and supports and resources needed to achieve each model. RESULTS: Clinicians described integrated care as an approach that incorporates elements of curative care, symptom and supportive care, advance care planning and end-of-life services from a multidisciplinary team. Analysis revealed two mental models that varied in how and when these constituents are delivered. One mental model involves sequential transitions between constituents of care, and the second mental model involves synchronous application of the various constituents. Participants described elements of teamwork and coordination supports necessary to achieve integrated AdvLD care. Many discussed the importance of having a multidisciplinary team integrating supportive care, symptom management and palliative care with liver disease care. CONCLUSIONS: Health professionals agree on the constituents of integrated AdvLD care but describe two competing mental models of how these constituents are integrated. Health systems can promote integrated care by assembling multidisciplinary teams, and providing teamwork and coordination supports, and training that facilitates patient-centred AdvLD care.

Novel colchicine derivative CR42-24 demonstrates potent anti-tumor activity in urothelial carcinoma.

Bladder cancers, and specifically urothelial carcinoma, have few effective treatment options, and tumors typically develop resistance against standard of care chemotherapies leading to significant mortality. The development of alternative therapies with increased selectivity and improved tolerability would significantly impact this patient population. Here, we investigate a novel colchicine derivative, CR42-24, with increased selectivity for the ßIII tubulin subtype as a treatment for urothelial carcinoma. ßIII tubulin is a promising target due to its low expression in healthy tissues and its clinical association with poor prognosis. This study demonstrated that CR42-24 is selectively cytotoxic to several cancer cell lines at low nanomolar IC50, with high activity in bladder cancer cell lines both in vitro and in vivo. CR42-24 monotherapy in an aggressive urothelial carcinoma xenograft model results in effective control when treated early. We observed significant ablation of large tumors and patient-derived xenografts at low doses with excellent tolerability. CR42-24 was highly synergistic in combination with the standard of care chemotherapies gemcitabine and cisplatin, further increasing its therapeutic potential as a novel treatment for urothelial carcinoma.

Vitamin D Supplement Use and Risk of Breast Cancer by Race-Ethnicity.

BACKGROUND: Vitamin D has anticarcinogenic properties, but a relationship between vitamin D supplement use and breast cancer is not established. Few studies have accounted for changes in supplement use over time or evaluated racial-ethnic differences. METHODS: The Sister Study is a prospective cohort of 50,884 women with 35-74 years of age who had a sister with breast cancer, but no breast cancer themselves at enrollment (2003-2009). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D supplement use and incident breast cancer (3,502 cases; median follow-up 10.5 years). RESULTS: Vitamin D supplement use was common, with 64% reporting ever use (at least once per month) in the year before enrollment. Considering supplement use over time, ever use of vitamin D supplements was not meaningfully associated with breast cancer (HR = 0.96, 95% CI = 0.88, 1.0), relative to never use. However, after adjusting for prior use, recent use of vitamin D supplements ≥1/month was inversely associated with breast cancer (HR = 0.88, 95% CI = 0.78, 1.0), relative to nonrecent use. The inverse association was stronger for ductal carcinoma in situ (HR = 0.67, 95% CI = 0.52, 0.87) than invasive breast cancer (HR = 0.94, 95% CI = 0.72, 1.1, p-for-heterogeneity = 0.02). Supplement use was less common among African American/Black (56%) and non-Black Hispanic/Latina (50%) women than non-Hispanic White women (66%), but there was limited evidence of racial-ethnic differences in HRs (p-for-heterogeneity = 0.16 for ever use, P = 0.55 for recent). CONCLUSIONS: Our findings are consistent with the hypothesis that recent vitamin D use is inversely associated with breast cancer risk.

Daily supplementation with the Lab4P probiotic consortium induces significant weight loss in overweight adults.

This 9-month randomised, parallel, double-blind, single-centre, placebo-controlled study (PROBE, ISRCTN18030882) assessed the impact of probiotic supplementation on bodyweight. Seventy overweight Bulgarian participants aged 45-65 years with BMI 25-29.9 kg/m2 received a daily dose of the Lab4P probiotic comprising lactobacilli and bifidobacteria (50 billion cfu/day). Participants maintained their normal diet and lifestyle over the duration of the study. The primary outcome was change from baseline in body weight and secondary outcomes included changes in waist circumference, hip circumference and blood pressure. A significant between group decrease in body weight (3.16 kg, 95% CI 3.94, 2.38, p < 0.0001) was detected favouring the probiotic group. Supplementation also resulted in significant between group decreases in waist circumference (2.58 cm, 95% CI 3.23, 1.94, p < 0.0001) and hip circumference (2.66 cm, 95% CI 3.28, 2.05, p < 0.0001) but no changes in blood pressure were observed. These findings support the outcomes of a previous shorter-term Lab4P intervention study in overweight and obese participants (PROMAGEN, ISRCTN12562026). We conclude that Lab4P has consistent weight modulation capability in free-living overweight adults.

Esophageal adenocarcinoma with any component of signet ring cells portends poor prognosis and response to neoadjuvant therapy.

BACKGROUND: Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even <50% would show resistance to standard multimodality therapy with poorer long-term outcomes. METHODS: Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC. RESULTS: SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P < .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival. CONCLUSIONS: We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated.

The characteristics of Queensland private physiotherapy practitioners' interprofessional interactions: a cross-sectional survey study.

Effective interprofessional collaboration (IPC) contributes to superior patient outcomes, facilitates cost-efficient health care, and increases patient and practitioner satisfaction. However, there is concern that IPC may be difficult to implement in clinical settings that do not conform to formal team-based processes, such as mono-professional physiotherapy private practice facilities. The aim of this study was to describe the characteristics of private physiotherapy practitioners' interprofessional interactions, including their experiences and perceptions regarding IPC. A custom developed cross-sectional online survey instrument was used to collect data from physiotherapists employed in private practice facilities in Queensland, Australia. In all, 49 (20% response rate) physiotherapists completed the survey. Only a small proportion (14%) indicated that their interprofessional interactions were a daily occurrence, and less than one-third of all respondents (31%) participated in formal, multi-professional face-to-face planned meetings. Most participants (76%) reported a moderate-to-high level of satisfaction regarding their interprofessional interactions. Despite low self-reported levels of interprofessional activity and other data indicating that IPC is necessary for holistic patient care, this study shows that physiotherapists were predominately satisfied when interacting with health practitioners from various professional backgrounds. Further research is required to inform the implementation of robust strategies that will support sustainable models of IPC in physiotherapy private practice.

Anandamide Metabolites Protect against Seizures through the TRP Channel Water Witch in Drosophila melanogaster.

Endocannabinoids protect against seizures, but their mechanism of action is still unclear, as they can have effects independent of known cannabinoid receptors. Using Drosophila melanogaster, which lacks canonical cannabinoid receptors, we report that the endocannabinoids anandamide and 2-arachidonoylglycerol protect against seizures in multiple fly seizure models. Surprisingly, inhibition of anandamide catabolism renders flies insensitive to protection by anandamide, indicating that anandamide metabolites are responsible for seizure protection. Consistent with this finding, arachidonic acid, a direct metabolite of anandamide, protects against seizures. To identify downstream effectors, we test for a role of transient receptor potential (TRP) channels and find that the TRPV1 antagonist capsazepine blocks the protective effect of anandamide. Also, a targeted genetic screen of TRP channels identifies water witch as a mediator of protection by anandamide. Using a Drosophila model, we reveal the role of arachidonic acid in seizure protection and identify a cannabinoid-receptor-1/2-independent mechanism of endocannabinoid seizure protection.

Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design.

The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mixed-solvent molecular dynamics simulations of the main protease (Mpro) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar severe acute respiratory syndrome (SARS) Mpro protein. In spite of a high level of sequence similarity, the active sites in both proteins showed major differences in both shape and size, indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the binding site's conformational changes during the simulation time indicated its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicated that the virus' mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design.

Discovery of a Bromodomain and Extraterminal Inhibitor with a Low Predicted Human Dose through Synergistic Use of Encoded Library Technology and Fragment Screening.

The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption of BET-KAc binding has emerged as an attractive therapeutic strategy with a number of small molecule inhibitors now under investigation in the clinic. However, until the utility of these advanced candidates is fully assessed by these trials, there remains scope for the discovery of inhibitors from new chemotypes with alternative physicochemical, pharmacokinetic, and pharmacodynamic profiles. Herein, we describe the discovery of a candidate-quality dimethylpyridone benzimidazole compound which originated from the hybridization of a dimethylphenol benzimidazole series, identified using encoded library technology, with an N-methyl pyridone series identified through fragment screening. Optimization via structure- and property-based design led to I-BET469, which possesses favorable oral pharmacokinetic properties, displays activity in vivo, and is projected to have a low human efficacious dose.

From clinical specimens to human cancer preclinical models-a journey the NCI-cell line database-25 years later.

The intramural the National Cancer Institute (NCI) and more recently the University of Texas Southwestern Medical Center with many different collaborators comprised a complex, multi-disciplinary team that collaborated to generated large, comprehensively annotated, cell-line related research resources which includes associated clinical, and molecular characterization data. This material has been shared in an anonymized fashion to accelerate progress in overcoming lung cancer, the leading cause of cancer death across the world. However, this cell line collection also includes a range of other cancers derived from patient-donated specimens that have been remarkably valuable for other types of cancer and disease research. A comprehensive analysis conducted by the NCI Center for Research Strategy of the 278 cell lines reported in the original Journal of Cellular Biochemistry Supplement, documents that these cell lines and related products have since been used in more than 14 000 grants, and 33 207 published scientific reports. This has resulted in over 1.2 million citations using at least one cell line. Many publications involve the use of more than one cell line, to understand the value of the resource collectively rather than individually; this method has resulted in 2.9 million citations. In addition, these cell lines have been linked to 422 clinical trials and cited by 4700 patents through publications. For lung cancer alone, the cell lines have been used in the research cited in the development of over 70 National Comprehensive Cancer Network clinical guidelines. Finally, it must be underscored again, that patient altruism enabled the availability of this invaluable research resource.

Human Induced Pluripotent Stem-Cardiac-Endothelial-Tumor-on-a-Chip to Assess Anticancer Efficacy and Cardiotoxicity.

Cancer remains a leading health threat in the United States, and cardiovascular drug toxicity is a primary cause to eliminate a drug from FDA approval. As a result, the demand to develop new anticancer drugs without cardiovascular toxicity is high. Human induced pluripotent stem (iPS) cell-derived tissue chips provide potentially a cost-effective preclinical drug testing platform, including potential avenues for personalized medicine. We have developed a three-dimensional microfluidic device that simultaneously cultures tumor cell spheroids with iPS-derived cardiomyocytes (iPS-CMs) and iPS-derived endothelial cells (iPS-EC). The iPS-derived cells include a GCaMP6 fluorescence reporter to allow real-time imaging to monitor intracellular calcium transients. The multiple-chambered tissue chip features electrodes for pacing of the cardiac tissue to assess cardiomyocyte function such as the maximum capture rate and conduction velocity. We measured the inhibition concentration (IC50) of the anticancer drugs, Doxorubicin (0.1 µM) and Oxaliplatin (4.2 µM), on the tissue chip loaded with colon cancer cells (SW620). We simultaneously evaluated the cardiotoxicity of these anticancer drugs by assessing the drug effect on the spontaneous beat frequency and conduction velocity of iPS-derived cardiac tissue. Consistent with in vivo observations, Doxorubicin reduced the spontaneous beating rate and maximum capture rate at or near the IC50 (0.04 and 0.22 µM, respectively), whereas the toxicity of Oxaliplatin was only observed at concentrations beyond the IC50 (33 and 9.9 µM, respectively). Our platform demonstrates the feasibility to simultaneously assess cardiac toxicity and antitumor effects of drugs and could be used to enhance personalized drug testing safety and efficacy. Impact statement Drug development using murine models for preclinical testing is no longer adequate nor acceptable both financially for the pharmaceutical industry as well as for generalized or personalized assessment of safety and efficacy. Innovative solutions using human cells and tissues provide exciting new opportunities. In this study, we report on the creation of a 3D microfluidic device that simultaneously cultures human tumor cell spheroids with cardiomyocytes and endothelial cells derived from the same induced pluripotent stem cell line. The platform provides the opportunity to assess efficacy of anticancer agents while simultaneously screening for potential cardiovascular toxicity in a format conducive for personalized medicine.

The association between coffee consumption and bladder cancer in the bladder cancer epidemiology and nutritional determinants (BLEND) international pooled study.

BACKGROUND: Inconsistent results for coffee consumption and bladder cancer (BC) risk have been shown in epidemiological studies. This research aims to increase the understanding of the association between coffee consumption and BC risk by bringing together worldwide case-control studies on this topic. METHODS: Data were collected from 13 case-control comprising of 5,911 cases and 16,172 controls. Pooled multivariate odds ratios (ORs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel logistic regression models. Furthermore, linear dose-response relationships were examined using fractional polynomial models. RESULTS: No association of BC risk was observed with coffee consumption among smokers. However, after adjustment for age, gender, and smoking, the risk was significantly increased for never smokers (ever vs. never coffee consumers: ORmodel2 1.30, 95% CI 1.06-1.59; heavy (> 4 cups/day) coffee consumers vs. never coffee consumers: ORmodel2 1.52, 95% CI 1.18-1.97, p trend = 0.23). In addition, dose-response analyses, in both the overall population and among never smokers, also showed a significant increased BC risk for coffee consumption of more than four cups per day. Among smokers, a significant increased BC risk was shown only after consumption of more than six cups per day. CONCLUSION: This research suggests that positive associations between coffee consumption and BC among never smokers but not smokers.

The Association of a Breast Cancer Diagnosis With Serum 25-Hydroxyvitamin D Concentration Over Time.

Prospective and retrospective studies of vitamin D levels and breast cancer have produced discrepant results. This may be due to variations in serum 25-hydroxyvitamin D (25(OH)D) concentrations over time, including systematic changes after breast cancer diagnosis. We measured total serum 25(OH)D levels in participants from the Sister Study, a US cohort study of sisters of breast cancer patients, who provided samples at baseline (2003-2009) and 4-10 years later (2013-2015). This included 827 women with an intervening breast cancer and 771 women without one. Although 25(OH)D levels were modestly correlated over time (R = 0.42), 25(OH)D concentrations increased in both groups, with larger increases among cases (averaging 31.6 ng/mL at baseline and 43.5 ng/mL at follow-up) than among controls (32.3 ng/mL at baseline, 40.4 ng/mL at follow-up). Consequently, the estimated association between 25(OH)D and breast cancer depended on whether baseline measurements (per 10-ng/mL increase, odds ratio = 0.87, 95% confidence interval: 0.78, 0.98) or measurements from the second blood draw (per 10-ng/mL increase, odds ratio = 1.17, 95% confidence interval: 1.08, 1.26) were used. Concentrations were related to regular use (≥4 times/week) of vitamin D supplements, which became more common over time; increases in regular use were greater in cases (from 56% to 84%) than in controls (from 56% to 77%). Our results do not explain previously observed differences between retrospective and prospective studies, but they do demonstrate how reverse causation and temporal trends in exposure can distort inference.

Relationship of Mindfulness to Distress and Cortisol Response in Adolescent Girls At-Risk for Type 2 Diabetes.

Altered stress response theoretically contributes to the etiology of cardiometabolic disease. Mindfulness may be a protective buffer against the effects of stress on health outcomes by altering how individuals evaluate and respond to stress. We engaged adolescent girls at risk for developing Type 2 diabetes in a cold-pressor test in order to determine the relationship of dispositional mindfulness to cortisol response and subjective stress, including perceived pain and unpleasantness during the stressor, and negative affect following the stressor. We also evaluated mindfulness as a moderator of psychological distress (depressive/anxiety symptoms) and stress response. Participants were 119 girls age 12-17 years with overweight/obesity, family history of diabetes, and mild-to-moderate depressive symptoms. Greater mindfulness was associated with less perceived pain and negative affect, but was unrelated to cortisol response to the stressor. Regardless of mindfulness, greater depressive/anxiety symptoms related to a more blunted cortisol response. Mindfulness might promote better distress tolerance in adolescents at risk for diabetes by altering how youth perceive and relate to acute stress, rather than through altering the physiological stress response. At all levels of mindfulness, depressive/anxiety symptoms relate to greater blunting of cortisol response. Findings contribute to emerging literature on the role of mindfulness in promoting the mental and physical health and well-being of individuals at risk for Type 2 diabetes.

Mindfulness and laboratory eating behavior in adolescent girls at risk for type 2 diabetes.

Mindfulness-based intervention has become increasingly popular to address disinhibited eating in obesity and type 2 diabetes (T2D). Theoretically, present-moment attention promotes the ability to recognize and respond to internal hunger cues and to differentiate physiological hunger from other stimuli. Yet, there is limited research describing the relationship of mindfulness with disinhibited eating patterns in adolescents. In this study, we evaluated the relationship of dispositional mindfulness to laboratory eating in 107 adolescent (12-17 years) girls at risk for T2D. Adolescents reported dispositional mindfulness, were evaluated for recent loss-of-control-eating (LOC-eating) by interview, and participated in two successive, standardized laboratory test meals to assess eating when hungry as well as eating in the absence of hunger (EAH). Adolescents rated state appetite throughout the test meal paradigms. In analyses adjusting for body composition and other possible confounds, mindfulness was inversely related to caloric intake during the EAH paradigm. Mindfulness did not relate to energy intake when hungry. Instead, there was a significant interaction of reported LOC-eating by state hunger, such that girls with recent, reported LOC-eating and high state hunger consumed more calories when hungry, regardless of mindfulness. Findings suggest that in girls at risk for T2D, mindfulness may play a role in disinhibited eating. A propensity for LOC-eating may be most salient for overeating in a high hunger state.