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BACKGROUND: The majority of Chinese Americans is foreign-born, and it is well-documented that immigration to the United States (US) leads to increased risk for chronic diseases including type 2 diabetes. Increased disease risk has been attributed to changes in lifestyle behaviors following immigration, but few studies have considered the psychosocial impact of immigration upon biomarkers of disease risk. PURPOSE: To examine associations of psychological stress and social isolation with markers of type 2 diabetes risk over time among US Chinese immigrants. METHODS: In this longitudinal study of 614 Chinese immigrants, participants completed assessments of perceived stress, acculturative stress, negative life events, and social isolation annually at three time points. Fasting blood samples were obtained at each time point to measure blood glucose, glycated hemoglobin, and insulin resistance. Mean duration between baseline and follow-up assessments was approximately 2 years. RESULTS: Increases in migration-related stress, perceived stress and social isolation were associated with significant increases in fasting glucose at follow-up independent of age, body mass index, length of US residence, and other potential covariates. Moreover, increases in glucose varied depending on perceived stress levels at baseline, such that those with higher baseline stress had a steeper increase in glucose over time. CONCLUSIONS: Psychological stress and social isolation are associated with increases in fasting glucose in a sample of US Chinese immigrants. Findings suggest that the unique experiences of immigration may be involved in the risk of developing type 2 diabetes, a condition that is prevalent among US Chinese despite relatively low rates of obesity.

Many Chinese Americans are born outside the United States (US), and moving to the US can increase their risk of chronic diseases like type 2 diabetes. This increased risk is often linked to lifestyle changes after immigration, but not much research has looked at how stress and social isolation may affect disease risk. We conducted a longitudinal study that followed 614 Chinese immigrants over a 2-year period to see if stress and social isolation were linked to diabetes risk. Participants filled out surveys about their levels of stress, social isolation, and any negative life events that had occurred, and had their blood tested for markers that are associated with diabetes risk. The study showed that higher stress and social isolation were linked to higher fasting glucose (blood sugar) levels, regardless of other factors like age or how long they had lived in the US. People who started with higher stress levels also had a bigger increase in fasting blood sugar levels over time. In summary, among Chinese immigrants in the US, stress and social isolation leads to increases in fasting blood sugar levels over time, which can be indicative of type 2 diabetes.

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INTRODUCTION: Most adrenal incidentalomas are not appropriately evaluated. Reporting the mass in the radiology report summary and providing recommendations in the report can positively impact evaluation. This study evaluated the effect of reporting Hounsfield units(HU) on adrenal incidentaloma follow-up. METHODS: Patients with adrenal incidentalomas identified on noncontrast CT scan from 2015 to 2020 â€‹at a tertiary care institution were studied. Chart review was conducted. Patient and imaging characteristics were compared between patients who did and did not have HU reported. Outcomes of interest were 1)outpatient referral, 2)biochemical evaluation, and 3)dedicated imaging if appropriate. Multivariate analysis determined the impact of HU, reporting in the summary and provision of recommendations on the outcomes. RESULTS: 363 patients were studied, 36(9.9 â€‹%) had HU reported. When HU were used in addition to recommendations and reporting in the summary, the likelihood of outpatient referral increased from 10.1 to 32.6-fold (95%CI 7.7-138.1, p â€‹< â€‹0.001). Similarly, the likelihood of biochemical workup increased from 2.5 to 7.8-fold (95%CI 2.5-24.1, p â€‹< â€‹0.001). CONCLUSION: Recording adrenal incidentaloma HU on non-contrast CT scans was associated with increased rates of outpatient referral and biochemical workup.

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Purpose: Evaluate the efficacy of transdermal patches containing ketoprofen and diclofenac sodium compared to oral diclofenac tablets in reducing post-endodontic pain after single-visit root canal therapy for teeth with symptomatic irreversible pulpitis. Methods: A total of 78 eligible participants with symptomatic irreversible pulpitis and preoperative VAS scores of 4 or above were enrolled after obtaining ethical approval (SVIEC/ON/DENT/SRP/22064) and CTRI registration (CTRI/2022/07/044231). Exclusion criteria included pregnancy, lactation, fractured/cracked teeth, developmental anomalies, tooth pathology, or ongoing analgesic/NSAID use. After root canal treatment, participants were randomized into three groups using computer randomization. Groups A and B received transdermal patches with Ketoprofen and diclofenac sodium, respectively, applied to the right forearm for 24 hours, with an additional patch on the left forearm for the next day. Group C received four diclofenac sodium oral tablets, twice daily for two days. VAS scales were used to assess pain at 4, 8, 24, and 48 hours post-treatment. The VAS scores collected were tabulated and statistically analyzed using SPSS version 21 with (P < 0.05). Shapiro Wilk test and the Related Samples Friedman's Two-Way Analysis of Variance by Ranks were used for statistical evaluation. Results: Statistically significant reductions in mean postoperative pain scores were observed across all groups at all time points compared to preoperative scores. Notably, the Ketoprofen patch group exhibited superior performance compared to the diclofenac transdermal patch and oral diclofenac tablet groups at 48 hours, with statistical significance (p=0.047). Conclusion: The present evidence substantiates the efficacy of transdermal patches containing diclofenac and ketoprofen in managing postoperative pain arising from symptomatic irreversible pulpitis in single-rooted teeth. By avoiding the use of oral NSAIDs, these patches provide effective pain relief while minimizing the risk of adverse effects, presenting a favorable option for patients.

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The current study, which lasted 45 days, was designed to find a more effective way to use the vast resources of salt-affected land and ground saline water for aquaculture. Biochar made from agrowaste was used as a sediment amendment. The 100 g of biochar was applied to 25 kg of sediment (i.e., 9.0 ton ha-1) in 300L capacity fiber reinforced plastic, and Penaeus vannamei (P. vannamei) (2.74 ± 0.03 g) was stocked at 90 juveniles m-2 in inland ground saline water of salinity 10 ppt fortified with potassium levels that are 50% equivalent to those of seawater. Among different treatments, T1 indicates paddy straw biochar (PSB) application in sediment; T2 indicates sediment amended with KOH-activated PSB; T3 indicates sugar cane bagasse biochar (SBB) application in sediment; and T4 indicates sediment amended with KOH-activated SBB. Compared to the control the potassium (K+), alkalinity, total hardness, calcium/magnesium ratio, and pH of the water increased significantly (P ≤ 0.05) in treatments where biochar was used as an amendment in sediment. The T3 treatment had the best Ca/Mg ratio (1.00:3.12). In water, the magnitude of increase in K+ concentration from high to low followed the order: T2 > T4 > T1 > T3 > control. The concentration of NH4+-N in water was found to be increasing in control, whereas in the rest of the treatments, it decreased significantly from day 1, until the end of the experiment. Compared to control, the bulk density was decreased, and sediment cation exchange capacity and water holding capacity were increased significantly in treatments where biochar was used as an amendment. The soil microbial parameter measured in terms of soil enzyme dehydrogenase was significantly different among treatments at the end of the experiment. Weight gain (%), specific growth rate (SGR), survival (%), and feed conversion ratio of P. vannamei varied significantly in T1, T2, T3, and T4 compared to the control. The SGR (2.38b ± 0.05% day-1) and weight gain (%) in T2, and survival (96.1b ± 2.0%) in T3 treatment were found to be the highest at the end of the experiment. When biochar was mixed with sediment in the inland saline system, an improvement was seen in sediment quality, water quality, and growth characteristics of P. vannamei.

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PURPOSE OF REVIEW: The purpose of this review will be to shed light on novel techniques for assessment of bone tissue material properties. RECENT FINDINGS: Recently there has been an increase in modalities to investigate bone tissue material properties. Historically, clinicians treating patients with bone disorders have relied upon the use of bone mineral density (BMD) as assessed by dual-energy X-ray absorptiometry (DXA). Although DXA provides an ability to screen at a large-scale population level, it only explains about 60% of the fracture risk. Recent advances include the use of imaging modalities, responses to load, and novel infrared (IR) techniques. SUMMARY: These newer techniques have not reached a point for population level screening; however, they may inform the science of bone biology further and help discern various bone disease states.

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BACKGROUND: Despite the University of California San Francisco, the American Academy of Pediatric Dentistry (AAPD), and the Food and Drug Administration having approved the use of silver diamine fluoride (SDF) in arresting dentinal caries, literature available on its systemic absorption is limited. AIM: This study aimed to assess any systemic absorption of fluoride ion following the topical application of SDF in young children. MATERIALS AND METHODS: Children aged between 3 and 6 years who were diagnosed with severe early childhood caries and required rehabilitation were recruited for the study. Before the onset of treatment for the arrest and control of caries, a baseline urine sample as a control was collected from the patient. In accordance with the manufacturer's instructions and AAPD guidelines, SDF was topically applied on a minimum of five carious teeth, following which additional urine samples were collected after 2 h and after 24 h, respectively, of application of SDF. The urine samples were stored at -20°C, and the estimation of fluoride ion concentrations in urine was then ascertained using a fluoride ion selective electrode. RESULTS: The results revealed that the fluoride concentration in urine before application of SDF was 0.66 mg/L ± 0.25 mg/L, and following 2 h of application, it was 1.13 mg/L ± 0.23. However, 24 h postapplication, the urinary fluoride concentration was reduced to 0.63 mg/L ± 0.20, which is close to the baseline value of the control sample. CONCLUSION: There was no significant systemic absorption of fluoride following the application of SDF, and it could be adopted as an effective and safe agent in the armamentarium for managing caries in young children.

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This study aimed to evaluate and compare two different fiber-reinforced composite materials in class I post-endodontic restoration in molars. A total of 50 patients were randomly assigned into two groups (n = 25 for each group); group A: everX Posterior (packable composite) with a top layer of solareX (nano-hybrid composite) and group B: everX Flow (flowable composite) with a top layer of G-aenial universal injectable (flowable composite). Patients were evaluated immediately after the procedure (baseline), at 6 months, and at 1 year time intervals based on the modified USPHS criteria. The statistical analysis using a chi-square test showed no statistically significant difference in the clinical performance of group A and group B. Clinical performance of the combination of everX Flow with overlying G-aenial universal injectable composite proved to be comparable with everX Posterior with overlying solareX composite as post-endodontic restorations in class I lesions in permanent molars.

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Aim: The Purpose of This In-Vitro Study Was to Comparatively Evaluate the Aesthetic Outcome Of Direct Polychromatic Layering Of Anterior Composites Restoration With The "Index Cut-Back" Technique While Restoring Class IV Defects of Teeth. Methodology: An extracted tooth specimen of maxillary central incisor crown was 3-D scanned for obtaining its dimensions, these dimensions were transferred to AUTOCAD™ software and a customised 3-D Printed mould was fabricated (Temporary Patent no. 336763-001 ). 50 specimens of Maxillary Central Incisor Crowns were then constructed with the help of Composite restorative material (Palfique Estelite LX5, Tokuyama Dental Corporation, Japan) in this mould. Afterwards with the help of a Straight fissure diamond bur a standardized size (4 cm length x 4 cm width) class IV defect was created on all 50 specimens and then they were allocated to 2 groups, Group A & B. 25 specimens for each Group (N = 25). Group A was restored using conventional Direct Polychromatic Layering technique and Group B was restored using the "Index cut-back" Technique. Shade Outcome and Translucency were evaluated using Spectrophotometer and Time taken was evaluated using a stop-watch chair side. Results: There was a significant difference in the values (P < .05) between Group A (Polychromatic) & Group B (Index cut-back) in terms of both Shade Outcome & Translucency; Group B showed better aesthetic values (closer to baseline) than Group A. In contrast, Time required for restoring the Class IV defects was significantly lower in Group A compared to Group B (P < .05). Conclusion: The Index Cut-Back Technique showed superior aesthetic outcome restoring Class IV defects, however it requires a planned pre-operative course of action before executing the clinical procedure.

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Aim: The aim of the study is to evaluate and compare the 1-year clinical performance of conventional direct composite restoration technique with a novel "custom shield" technique in class I compound lesions. Subjects and Methods: After ethical approval, 72 patients who signed the informed consent form participated in the study. They were divided into two groups - Group A: Conventional direct composite restoration (n = 36) and Group B: Composite restoration using custom shield technique (n = 36) by computer randomization. In Group A, composite restoration was performed by the incremental layering technique. In Group B, restoration was performed using a novel custom shield and occlusal stamp along with the incremental layering technique. Patients were evaluated using the modified USPHS criteria by blinded evaluators for 1 year. Statistical Analysis: Chi-square test and Friedman test using SPSS version 21.0. Results: A statistically significant difference was obtained for marginal adaptation (P = 0.024), retention (P = 0.23), surface texture, and anatomic form (P < 0.001), and time taken to perform the procedure for Group B was higher than Group A. Conclusion: Conventional composite restoration and custom shield technique can be successfully used in class I compound lesions with custom shield technique having a higher edge over the conventional technique.

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G-protein coupled receptor (GPCR) kinase 2 (GRK2) is upregulated in heart failure (HF) patients and mouse models of cardiac disease. GRK2 is a regulator of ß-adrenergic receptors (ßARs), a GPCR involved in ionotropic and chronotropic responses. We and others have recently reported GRK2 to be localized in the mitochondria, although its function in the mitochondria and/or metabolism remain not clearly defined. We hypothesized that upregulation of GRK2 reduced mitochondrial respiratory function and responses to ßAR activation. Utilizing isolated mouse primary adult cardiomyocytes (ACMs), we investigated the role of glucose, palmitate, ketone bodies, and BCAAs in mediating cell survival. Our results showed that myocyte upregulation of GRK2 promotes palmitate-induced cell death. Isotopologue labeling and mass spectrometry showed that the upregulation of GRK2 reduces ß-hydroxybutyryl CoA generation. Next, using isoproterenol (ISO), a non-selective ßAR-agonist, we determined mitochondrial function in mouse and human primary ACMs. Upregulation of GRK2 impaired ISO-mediated mitochondrial functional responses, which we propose is important for metabolic adaptations in pathological conditions. Increased cardiac levels of GRK2 reduced fatty acid-specific catabolic pathways and impaired ISO-stimulated mitochondrial function. Our data support the notion that GRK2 participates in bioenergetic remodeling and may be an important avenue for the development of novel pharmacological strategies in HF.

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The USA has among the largest immigrant population of any country in the world, and over the past few decades, the proportion of Chinese immigrants in the USA has increased significantly. Immigrants may experience substantial acculturative stress as they learn to navigate their new environment, and this stress can contribute to depressive symptoms and poor mental health. Social support can help mitigate the effects of stress on depressive symptoms, but the protective effects of social support have been reported to differ between men and women. Thus, the present study examined associations of acculturative stress and depressive symptoms among Chinese immigrants and explored whether the effects of social support on depressive symptoms varied by gender. Participants included 620 foreign-born Chinese men and women who completed questionnaires on acculturative stress, social support, and depressive symptoms. In nested regression analyses, acculturative stress was positively associated with depressive symptoms among both men and women. However, the interaction of social support and acculturative stress on depressive symptoms was statistically significant among men (ß = - 0.89, p < 0.001), but not women (ß = - 0.43, p = 0.21). These findings suggest that social support moderates the association of acculturative stress with depressive symptoms, but only among Chinese immigrant men. Future research should explore factors that can enhance resilience and mitigate acculturative stress effects on psychological well-being among Chinese immigrant women.

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Research efforts in the twenty-first century have been paramount to the discovery and development of novel pharmacological treatments in a variety of diseases resulting in improved life expectancy. Yet, cardiac disease remains a leading cause of morbidity and mortality worldwide. Over time, there has been an expansion in conditions such as atrial fibrillation (AF) and heart failure (HF). Although past research has elucidated specific pathways that participate in the development of distinct cardiac pathologies, the exact mechanisms of action leading to disease remain to be fully characterized. Protein turnover and cellular bioenergetics are integral components of cardiac diseases, highlighting the importance of mitochondria and endoplasmic reticulum (ER) in driving cellular homeostasis. More specifically, the interactions between mitochondria and ER are crucial to calcium signaling, apoptosis induction, autophagy, and lipid biosynthesis. Here, we summarize mitochondrial and ER functions and physical interactions in healthy physiological states. We then transition to perturbations that occur in response to pathophysiological challenges and how this alters mitochondrial-ER and other intracellular organelle interactions. Finally, we discuss lifestyle interventions and innovative therapeutic targets that may be used to restore beneficial mitochondrial and ER interactions, thereby improving cardiac function.

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AIM AND OBJECTIVE: This study aimed to compare the apical sealing ability and periapical extrusion in the Thermafil™ obturation technique, with and without an apical barrier of MTA, with lateral condensation technique. MATERIALS AND METHODS: Sixty freshly extracted human central incisors were instrumented with the crown down technique and divided into three experimental groups. Group I: lateral condensation technique obturation, group II: Thermafil obturation (DENTSPLY Tulsa), and group III: this group was obturated into two parts; first MTA (ProRoot) was placed in apical 3 mm and later the remaining canal was obturated with Thermafil™ obturation technique (DENTSPLY Tulsa). AH Plus sealer was used in all the groups. Specimens of all the groups were layered with nail paint excluding the apical 3 mm. Twenty-four hours later, all the teeth were suspended in Black India ink for 48 hours. Finally, all the teeth were decalcified, rendered transparent and linear dye leakage and periapical extrusion was measured using ×60 magnification of stereomicroscope with an in-built ruler. RESULTS: A Chi-square test done to evaluate periapical extrusion showed there was a significant difference found among all the groups (p < 0.05), whereas in case of linear apical dye leakage using a Student's "t" test showed there was no significant difference among all the groups (p > 0.05). CONCLUSION: Despite showing apical leakage, the thermo-plasticized gutta-percha obturation technique can be advantageous when used with MTA as an apical barrier since there is no scope for apical extrusion along with the benefit of three-dimensional obturation of the root canal system when compared with the lateral condensation technique. HOW TO CITE THIS ARTICLE: Rao AS, Mathur R, Shah NC, et al. Evaluation of Extrusion and Apical Seal of Thermafil™ Obturation with and without MTA as an Apical Barrier in Comparison with Lateral Condensation Technique: An In Vitro Study. Int J Clin Pediatr Dent 2020;13(S-1):S40-S44.

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AIM: The aim of this study was to compare and evaluate the clinical performance of nanohybrid composite with Activa™ bioactive composites in Class II carious lesion. METHODOLOGY: After ethical approval, patients were selected according to the inclusion-exclusion criteria with minimum of two carious lesions in a single patient. Lesions were randomly divided into two groups: Group A - nanohybrid composite and Group B - Activa™ bioactive composite. After administration of local anesthetic agent, Class II cavity preparation was done followed by rubber dam application. For deep lesion, pulp protection was done with light-cured calcium hydroxide. Then, the cavities were restored. Finishing and polishing were done. Evaluation of the restorations was done at 1 week, 6 months, and 1 year time interval by second-blinded examiner according to the modified USPHS criteria. The results of the study were tabulated, and statistical analysis was done. RESULTS: The results showed no statistically significant difference in the clinical performance of nanohybrid composite and Activa™ bioactive composites in Class II carious lesions at the end of 1 week, 6 months, and 1 year. CONCLUSION: It can be concluded that both materials showed equal and acceptable clinical performance at the end of 1 year. Both materials can be successfully be used to restore Class II carious lesions.

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Cardiovascular (CV) disease fatality rates are higher for women compared with men with diabetes despite lower rates of obstructive coronary artery disease (CAD). Impaired coronary flow reserve (CFR), the ratio of adenosine-stimulated to rest myocardial blood flow (MBF), is an indicator of coronary microvascular dysfunction and predicts major adverse CV events. We performed a post hoc analysis to determine whether there was a sex disparity in coronary microvascular dysfunction among 46 men and 27 women with well-controlled type 2 diabetes and without clinical evidence of obstructive CAD. We found that women had a higher rest MBF, lower CFR, and worse diastolic function compared with men. In addition, rest MBF was positively correlated with worse diastolic function in women. We previously showed that mineralocorticoid blockade improved CFR in men and women with type 2 diabetes, implicating aldosterone in the pathophysiology of coronary microvascular dysfunction. We therefore examined aldosterone levels and found that women had larger increases in aldosterone in response to an angiotensin-II infusion than did men. In conclusion, among individuals with type 2 diabetes and good cardiometabolic control, women had worse myocardial perfusion and diastolic function compared with men. The greater aldosterone responsivity in women may be a mechanism for this sex effect.

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INTRODUCTION: Individuals with diabetes are at increased risk for complications, including gastroparesis. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulting in decreased beta-cell function. Glutamic acid decarboxylase-65 antibody (GADA) is the most commonly used test to assess autoimmunity while C-peptide level is used to assess beta-cell function. Patients with type 2 diabetes mellitus (T2DM), who are GADA positive, are labeled latent autoimmune diabetes in adults (LADA). OBJECTIVE: To characterize patients with T1 and T2DM who have symptoms of gastroparesis using GADA and C-peptide levels and to look for association with the presence of gastroparesis and its symptom severity. DESIGN: 113 T1DM and 90 T2DM patients with symptoms suggestive of gastroparesis were studied. Symptom severity was assessed using Gastroparesis Cardinal Symptom Index (GCSI). Serum samples were analyzed for GADA and C-peptide. RESULTS: Delayed gastric emptying was present in 91 (81%) of T1DM and 60 (67%) of T2DM patients (p = 0.04). GADA was present in 13% of T2DM subjects [10% in delayed gastric emptying and 20% in normal gastric emptying (p = 0.2)]. Gastric retention and GCSI scores were mostly similar in GADA positive and negative T2DM patients. GADA was present in 45% of T1DM subjects [46% in delayed gastric emptying and 41% in normal gastric emptying (p = 0.81)]. Low C-peptide levels were seen in 79% T1DM patients and 8% T2DM. All seven T2DM patients with low C-peptide were taking insulin compared to 52% of T2DM with normal C-peptide. CONCLUSION: GADA was present in 13% while low C-peptide was seen in 8% of our T2DM patients with symptoms of gastroparesis. Neither did correlate with degree of delayed gastric emptying or symptom severity. CLINICALTRIALSGOV IDENTIFIER: NCT01696747.

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BACKGROUND: Advances in cancer immunotherapy have generated encouraging results in multiple malignancies refractory to standard chemotherapies. As the use of immune checkpoint inhibitors (ICI) proliferates, the incidence of autoimmune side effects associated with these agents, termed immune related adverse events (irAE), is expected to increase. The frequency of significant irAE in ICI treated patients is about 10-20% and early recognition is critical to prevent serious morbidity and even mortality. New onset autoimmune diabetes mellitus (DM) associated with immune checkpoint inhibitor treatment is extremely rare, occurring in less than 1% of patients. Autoimmune DM often presents as diabetic ketoacidosis, a medical emergency requiring immediate treatment. We describe the first reported case of a patient with lung cancer who developed autoimmune diabetes after nivolumab treatment and was found to have three diabetes related (islet) autoantibodies present before ICI treatment and seroconversion of another after ICI treatment and onset of autoimmune DM. CASE PRESENTATION: A 34 year old African American woman with metastatic non-small cell lung cancer (NSCLC) was treated with nivolumab in the second line setting after disease progression following standard chemoradiation therapy. After receiving two doses of nivolumab, the patient developed abrupt onset of hyperglycemia and diabetic ketoacidosis. Autoimmune diabetes was diagnosed on the basis of undetectable C-peptide levels, seropositivity of three diabetes related (islet) autoantibodies and absolute insulin dependence. The patient eventually required use of continuous subcutaneous insulin infusion (insulin pump) due to erratic glycemic excursions and multiple readmissions for DKA. Human leucocyte antigen (HLA) genoyping revealed none of the high risk haplotypes associated with the development of type 1 diabetes. Interestingly, a frozen blood sample obtained prior to treatment with nivolumab tested positive for three of the four diabetes related (islet) autoantibodies despite no prior history of diabetes and no family history of diabetes. Notably, at the time of manuscript preparation, the patient is without evidence of NSCLC recurrence with no further treatment since the nivolumab therapy. CONCLUSION: New onset autoimmune diabetes mellitus associated with nivolumab has been described only in case reports and occurs at rates of < 1% in the large clinical trials which garnered FDA approval in the second line setting for NSCLC. As ICI use continues to expand across a wide variety of malignancies, clinicians must maintain a high index of suspicion for irAE, including autoimmune DM and other endocrinopathies. A multidisciplinary team and thorough education of the patient are recommended to optimize management of new onset adult autoimmune DM. Our patient may have been at greater risk for the development of ICI related autoimmune diabetes due to the presence of three diabetes related autoantibodies prior to therapy; however, about half of the reported cases of autoimmune DM after anti-PD-1 therapy occurred in patients with no detectable diabetes related autoantibodies. Further studies are needed to delineate genetic and immunologic biomarkers that may be useful in identifying patients at risk of developing ICI related autoimmune DM.

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BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is implicated in the pathophysiology of cardiovascular disease (CVD) and increased in individuals with type 2 diabetes mellitus (T2DM). Adipose tissue produces PAI-1, and pericardial fat is a CVD risk factor. We sought to determine the relationship between PAI-1 and pericardial fat in males and females with well-controlled T2DM. METHODS: The study population consisted of 32 males and 19 females, aged 35-70 years with T2DM, without clinical evidence of CVD or other active medical problems except for hypertension. Subjects were studied under good cardiometabolic control. Study procedures included fasting blood work and cardiovascular imaging. Cardiac magnetic resonance imaging of the heart was used to identify and quantify pericardial fat from the bifurcation of the pulmonary trunk to the last slice containing cardiac tissue. RESULTS: PAI-1 was positively correlated with pericardial fat (ß = 0.72, r = 0.72, P < 0.001) as well as with homeostatic model assessment of insulin resistance (r = 0.31, P = 0.03) and serum triglycerides (r = 0.27, P = 0.05). In a multivariable regression model, controlling for insulin sensitivity, triglycerides, and body mass index, pericardial fat was independently associated with PAI-1 (ß = 0.80, P < 0.001). CONCLUSIONS: PAI-1 is positively associated with pericardial fat in individuals with T2DM.

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The transcription factor TCF7L1 is an embryonic stem cell signature gene that is upregulated in multiple aggressive cancer types, but its role in skin tumorigenesis has not yet been defined. Here we document TCF7L1 upregulation in skin squamous cell carcinoma (SCC) and demonstrate that TCF7L1 overexpression increases tumor incidence, tumor multiplicity, and malignant progression in the chemically induced mouse model of skin SCC. Additionally, we show that downregulation of TCF7L1 and its paralogue TCF7L2 reduces tumor growth in a xenograft model of human skin SCC. Using separation-of-function mutants, we show that TCF7L1 promotes tumor growth, enhances cell migration, and overrides oncogenic RAS-induced senescence independently of its interaction with ß-catenin. Through transcriptome profiling and combined gain- and loss-of-function studies, we identified LCN2 as a major downstream effector of TCF7L1 that drives tumor growth. Our findings establish a tumor-promoting role for TCF7L1 in skin and elucidate the mechanisms underlying its tumorigenic capacity.

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