7 results on '"Bynoe, K."'
Search Results
2. Inducing remission of Type 2 diabetes in the Caribbean: findings from a mixed methods feasibility study of a low‐calorie liquid diet‐based intervention in Barbados.
- Author
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Bynoe, K., Unwin, N., Taylor, C., Murphy, M. M., Bartholomew, L., Greenidge, A., Abed, M., Jeyaseelan, S., Cobelli, C., Dalla Man, C., and Taylor, R.
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BLOOD sugar , *CONFIDENCE intervals , *INGESTION , *INTERVIEWING , *RESEARCH methodology , *TYPE 2 diabetes , *REDUCING diets , *WEIGHT loss , *PILOT projects , *THEMATIC analysis , *TREATMENT effectiveness , *DISEASE remission , *DESCRIPTIVE statistics - Abstract
Aim: In a high proportion of people with recently diagnosed Type 2 diabetes, a short (2–3‐month) low‐calorie diet is able to restore normal glucose and insulin metabolism. The aim of this study was to determine the feasibility of this approach in Barbados. Methods: Twenty‐five individuals with Type 2 diabetes diagnosed within past 6 years, not on insulin, BMI ≥ 27 kg/m2 were recruited. Hypoglycaemic medication was stopped on commencement of the 8‐week liquid (760 calorie) diet. Insulin response was assessed in meal tests at baseline, 8 weeks and 8 months. Semi‐structured interviews, analysed thematically, explored participants' experiences. 'Responders' were those with fasting plasma glucose (FPG) < 7 mmol/l at 8 weeks. Results: Ten men and 15 women (mean age 48, range 26–68 years) participated. Mean (sd) BMI was 34.2 kg/m2 (6.0); FPG 9.2 mmol/l (2.2). Mean weight loss at 8 weeks and 8 months was 10.1 kg [95% confidence interval (CI) 8.1, 12.0] and 8.2 kg (95% CI 5.8, 10.6); FPG was lower by 2.2 mmol/l (95% CI 1.2, 3.2) and 1.7 mmol/l (95% CI 0.8, 2.7) respectively. Nine of 11 (82%) of those who lost ≥ 10 kg were 'responders' compared with 6 of 14 (43%) who lost < 10 kg (P = 0.048). The 30‐min insulin increment was higher in responders at baseline and follow‐up (P ≤ 0.01). A food culture based on starchy foods and pressures to eat large amounts at social events were among the challenges identified by participants. Conclusions: The feasibility of this approach to weight loss and diabetes remission in a predominantly black population in Barbados was demonstrated. What's new?: Studies of the remission of Type 2 diabetes through dietary means in people with a recent diagnosis have, to date, been conducted in predominantly white populations in the UK.In a predominantly black Caribbean population with Type 2 diabetes, diet‐induced mean weight loss of 10 kg was associated with remission (fasting plasma glucose < 7.0 mmol/l) in 60% of participants at 8 weeks, and 38% at 8 months.Negative peer pressure in social situations was one of several challenges participants reported.Remission of Type 2 diabetes is possible in this population.Further support to achieve and maintain greater weight loss is desirable. [ABSTRACT FROM AUTHOR]
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- 2020
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3. A checklist that enhances the provision of education during insulin initiation simulation: a randomized controlled trial
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Taylor, C. G., primary, Bynoe, K., additional, Worme, A., additional, Hambleton, I., additional, Atherley, A., additional, Husbands, A., additional, and Unwin, N., additional
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- 2015
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4. A checklist that enhances the provision of education during insulin initiation simulation: a randomized controlled trial.
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Taylor, C. G., Bynoe, K., Worme, A., Hambleton, I., Atherley, A., Husbands, A., and Unwin, N.
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DIABETES & psychology , *CONFIDENCE intervals , *INSULIN , *PATIENT education , *PHYSICIANS , *REPORT writing , *RESEARCH funding , *DATA analysis , *ACCESS to information , *RANDOMIZED controlled trials , *HUMAN research subjects , *PATIENT selection , *DESCRIPTIVE statistics - Abstract
Aim The study tested the hypothesis that doctors using an insulin information checklist during simulated insulin initiation would impart more information regarding insulin use. Methods A total of 128 simulations were conducted. Doctors ( n = 64) were recruited from practitioners recently completing internship ( n = 19) and those established in primary care ( n = 45). Both groups of doctors were strata randomized to control ( n = 32) and intervention groups ( n = 32), so that each group contained equal numbers. Doctors in each group experienced two identical simulations of insulin initiation with an intervening period of 10 min. Doctors in the intervention arm were introduced to an insulin initiation checklist, which they reviewed independently and utilized in the second simulation. Trained assessors captured the provision of education in 21 predefined educational areas. Differences in the change of the total education provided between the first and second simulations were assessed using linear regression. Results The difference in the mean change of education provided between the first and second simulations within the 21 educational areas for the control and treatment groups was 9.7 [95% confidence interval ( CI): 8.8-11.1, P < 0.001] - an increase of 46.2%. The difference for the 15 areas relevant to pen use was 7.3 (95% CI: 6.2-8.4, P < 0.001) - an increase of 51.6%. Conclusions The checklist resulted in doctors providing significantly more education applicable to syringe and insulin pen routes of insulin administration during simulations. Further research is needed on the checklist's impact on healthcare professionals and patient outcomes in the clinical context. (Clinical Trials Registry No: NCT02266303) [ABSTRACT FROM AUTHOR]
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- 2016
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5. Association of systemic and demographic risk factors with prevalence of retinopathy in US adults with prediabetes.
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Bynoe K, Wang J, and Sachdeva MM
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Background/objectives: To investigate the relative contribution of systemic risk factors to retinopathy in prediabetes using a nationally representative cohort in the US., Subjects/methods: A group of 2098 participants aged ≥40 years with available HbA1c and gradable retinal images from the National Health and Nutrition Examination Survey 2005-2008 were included in this retrospective cross-sectional analysis. Participants were stratified into control, prediabetes, and diabetes groups based on HbA1c and anti-hyperglycaemic medication use. Logistic regression was used to assess the contribution of potential systemic risk factors to retinopathy prevalence., Results: The prevalence of retinopathy in the prediabetes group was 7.69%. Multivariable logistic regression revealed an inverse association of female sex (OR, 0.25; 95% CI, 0.08-0.74; p = 0.02), eGFR (OR, 0.98; 95% CI, 0.96-1.00; p = 0.04), and fasting glucose levels (OR, 0.92; 95% CI 0.87-0.98; p = 0.02) with retinopathy in individuals with prediabetes and a positive association with a Race/Ethnicity classification of "Other" (OR, 6.05; 95% CI, 1.65-22.1; p = 0.01). Comparison of ORs between groups indicated differential associations of "Other" race, fasting glucose, and C-reactive protein (CRP) with retinopathy in prediabetes compared with diabetes., Conclusions: The prevalence of retinopathy among individuals with prediabetes in the NHANES database is similar to other studies. Our findings suggest that nonglycemic metabolic risk factors may be especially relevant to the risk of retinopathy in prediabetes and extend the previously suggested protective effect of female sex on retinopathy in diabetes to prediabetes. The increased odds of retinopathy in underrepresented racial/ethnic groups in the setting of prediabetes also have implications for risk assessment in this population., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)
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- 2024
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6. Suppression of Tumor Cell Lactate-generating Signaling Pathways Eradicates Murine PTEN/p53-deficient Aggressive-variant Prostate Cancer via Macrophage Phagocytosis.
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Chaudagar K, Hieromnimon HM, Kelley A, Labadie B, Shafran J, Rameshbabu S, Drovetsky C, Bynoe K, Solanki A, Markiewicz E, Fan X, Loda M, and Patnaik A
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- Animals, Humans, Male, Mice, Androgen Antagonists, beta Catenin metabolism, Cell Line, Tumor, Lactates, Lead metabolism, Macrophages metabolism, Mitogen-Activated Protein Kinase Kinases metabolism, Phagocytosis, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism, Proteomics, PTEN Phosphohydrolase metabolism, Signal Transduction, Prostatic Neoplasms drug therapy, Prostatic Neoplasms genetics, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism
- Abstract
Purpose: Phosphatase and tensin homolog (PTEN) loss-of-function/PI3K pathway hyperactivation is associated with poor therapeutic outcomes and immune checkpoint inhibitor resistance across multiple malignancies. Our prior studies in Pb-Cre;PTENfl/flTrp53fl/fl genetically engineered mice (GEM) with aggressive-variant prostate cancer (AVPC) demonstrated tumor growth control in 60% mice following androgen deprivation therapy/PI3K inhibitor (PI3Ki)/programmed cell death protein 1 (PD-1) antibody combination, via abrogating lactate cross-talk between cancer cells and tumor-associated macrophages (TAM), and suppression of histone lactylation (H3K18lac)/phagocytic activation within TAM. Here, we targeted immunometabolic mechanism(s) of PI3Ki resistance, with the goal of durable tumor control in AVPC., Experimental Design: Pb-Cre;PTENfl/flTrp53fl/fl GEM were treated with PI3Ki (copanlisib), MEK inhibitor (trametinib) or Porcupine inhibitor (LGK'974) singly or their combinations. MRI was used to monitor tumor kinetics and immune/proteomic profiling/ex vivo coculture mechanistic studies were performed on GEM tumors or corresponding tumor-derived cell lines., Results: Given our proteomic profiling showing persistent MEK signaling within tumors of PI3Ki-resistant GEM, we tested whether addition of trametinib to copanlisib enhances tumor control in GEM, and we observed 80% overall response rate via additive suppression of lactate within TME and H3K18lac within TAM, relative to copanlisib (37.5%) monotherapy. The 20% resistant mice demonstrated feedback Wnt/β-catenin activation, resulting in restoration of lactate secretion by tumor cells and H3K18lac within TAM. Cotargeting Wnt/β-catenin signaling with LGK'974 in combination with PI3Ki/MEKi, demonstrated durable tumor control in 100% mice via H3K18lac suppression and complete TAM activation., Conclusions: Abrogation of lactate-mediated cross-talk between cancer cells and TAM results in durable ADT-independent tumor control in PTEN/p53-deficient AVPC, and warrants further investigation in clinical trials., (©2023 American Association for Cancer Research.)
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- 2023
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7. Reversal of Lactate and PD-1-mediated Macrophage Immunosuppression Controls Growth of PTEN/p53-deficient Prostate Cancer.
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Chaudagar K, Hieromnimon HM, Khurana R, Labadie B, Hirz T, Mei S, Hasan R, Shafran J, Kelley A, Apostolov E, Al-Eryani G, Harvey K, Rameshbabu S, Loyd M, Bynoe K, Drovetsky C, Solanki A, Markiewicz E, Zamora M, Fan X, Schürer S, Swarbrick A, Sykes DB, and Patnaik A
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- Male, Animals, Mice, Humans, Tumor Suppressor Protein p53 genetics, Proto-Oncogene Proteins c-akt, Androgen Antagonists therapeutic use, Lactic Acid, Phosphatidylinositol 3-Kinases, Proteomics, Wnt Signaling Pathway, Immunosuppression Therapy, Macrophages pathology, PTEN Phosphohydrolase genetics, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant pathology
- Abstract
Purpose: Phosphatase and tensin homolog (PTEN) loss of function occurs in approximately 50% of patients with metastatic castrate-resistant prostate cancer (mCRPC), and is associated with poor prognosis and responsiveness to standard-of-care therapies and immune checkpoint inhibitors. While PTEN loss of function hyperactivates PI3K signaling, combinatorial PI3K/AKT pathway and androgen deprivation therapy (ADT) has demonstrated limited anticancer efficacy in clinical trials. Here, we aimed to elucidate mechanism(s) of resistance to ADT/PI3K-AKT axis blockade, and to develop rational combinatorial strategies to effectively treat this molecular subset of mCRPC., Experimental Design: Prostate-specific PTEN/p53-deficient genetically engineered mice (GEM) with established 150-200 mm3 tumors, as assessed by ultrasound, were treated with either ADT (degarelix), PI3K inhibitor (copanlisib), or anti-PD-1 antibody (aPD-1), as single agents or their combinations, and tumors were monitored by MRI and harvested for immune, transcriptomic, and proteomic profiling, or ex vivo co-culture studies. Single-cell RNA sequencing on human mCRPC samples was performed using 10X Genomics platform., Results: Coclinical trials in PTEN/p53-deficient GEM revealed that recruitment of PD-1-expressing tumor-associated macrophages (TAM) thwarts ADT/PI3Ki combination-induced tumor control. The addition of aPD-1 to ADT/PI3Ki combination led to TAM-dependent approximately 3-fold increase in anticancer responses. Mechanistically, decreased lactate production from PI3Ki-treated tumor cells suppressed histone lactylation within TAM, resulting in their anticancer phagocytic activation, which was augmented by ADT/aPD-1 treatment and abrogated by feedback activation of Wnt/β-catenin pathway. Single-cell RNA-sequencing analysis in mCRPC patient biopsy samples revealed a direct correlation between high glycolytic activity and TAM phagocytosis suppression., Conclusions: Immunometabolic strategies that reverse lactate and PD-1-mediated TAM immunosuppression, in combination with ADT, warrant further investigation in patients with PTEN-deficient mCRPC., (©2023 American Association for Cancer Research.)
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- 2023
- Full Text
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