Carbohydrate profiling & glycaemic indices of selected traditional Indian foods.

Background & objectives: Consumption of high glycaemic index (GI) food is associated with a high risk for diabetes. There is a felt need to understand the GI of common Indian traditional foods using standard GI protocols. The present study was aimed to analyse the carbohydrate profile of common traditional Indian food preparation and to determine their GI using standardized protocols. Methods: Twelve food preparations made of millets, wheat, maize and pulses were evaluated for nutrient composition including detailed carbohydrate profiling and tested for GI in healthy volunteers using standard methodology. Capillary blood glucose responses for the test foods containing 50 g available carbohydrates were recorded and compared to the reference food (50 g glucose). GI was calculated from the incremental area under the curve (IUAC) for the test and reference foods. Results: Available carbohydrate content of the food preparations ranged between 13.6 and 49.4 g per cent. Maize roti showed the highest total dietary fibre (7.5 g%). White chick pea 'sundal' showed highest resistant starch content (3.95 g%). Amongst the 12 test foods, five fell in the high GI category (finger millet balls, sorghum, pearl millet and maize roti), four in the medium GI category (sorghum idli, wheat dosa, methi roti and adai) and three in the low GI category (broken wheat upma, white peas sundal and white chick peas sundal). Interpretation & conclusions: Merely being a whole grain-based food does not qualify for a lower GI. The method of processing, food structural integrity and preparation could influence the GI. The type and quality of fibre are important than the quantity of fibre alone. Judicious planning of accompaniments using low GI legumes may favourably modify the glycaemic response to high GI foods in a meal.

The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER): Study Design and Protocol.

BACKGROUND: The SINgapore GERiatric intervention study to reduce cognitive decline and physical frailty (SINGER) randomised controlled trial (RCT) uses a multidomain lifestyle interventions approach, shown to be effective by the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial, to delay cognitive decline. OBJECTIVE: To investigate the efficacy and safety of the SINGER multidomain lifestyle interventions in older adults at risk for dementia to delay cognitive decline. PARTICIPANTS: 1200 participants between 60-77 years old, with Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score ≥6, fulfilling at least one of the following LIBRA index for diet, cognitive activity, physical activity and a Montreal Cognitive Assessment (MoCA) score ≥18, ≤27 points, will be recruited across Singapore. METHODS: SINGER is a 2-year multi-site RCT consisting of multidomain interventions: dietary advice, exercise, cognitive training, and vascular risk factors management. Participants will be randomised into either the Self-Guided Intervention (SGI; general lifestyle and health information and resources) or Structured Lifestyle Intervention (SLI) group. The SLI comprises diet training (6 group and 3 individual sessions over 12 months); exercise (supervised: 1-hour twice weekly for 6 months, unsupervised: 2-3/week for the rest of the study duration); cognitive sessions (15-30 minutes/session, 3/week for 6 months, together with 10 workshops in 24 months). Vascular management takes place every 3-6 months or otherwise as specified by study physicians. The primary outcome is global cognition measured using the modified Neuropsychological Battery assessing performance in various domains, such as episodic memory, executive function and processing speed. Secondary outcome measures include: domain-specific cognition and function, imaging evidence of brain and retinal changes, incidence and progression of chronic diseases, blood biomarkers, quality of life, mental health and cost-benefit analysis. CONCLUSIONS: SINGER is part of the Worldwide-FINGERS international network, which is at the forefront of harmonizing approaches to effective non-pharmacological interventions in delaying cognitive decline in older adults at risk of dementia. By establishing the efficacy of multidomain interventions in preventing cognitive decline, SINGER aims to implement the findings into public health and clinical practices by informing policy makers, and guiding the design of community- and individual-level health promotion initiatives.

Donor-site local anaesthetic infusion catheter as an opioid-sparing agent in free flap reconstruction of the head and neck: a valuable adjunct to an enhanced recovery protocol.

This paper presents the results of a retrospective case-controlled cohort study to investigate the effectiveness of a donor-site local anaesthetic infusion protocol to reduce opioid requirements, length of intensive therapy unit (ITU) stay, and incidence of postoperative delirium. Adult free flap head and neck patients were identified from a prospective database (n = 86). There was a significant reduction in mean opioid requirements (p < 0.001). Postoperative delirium was observed in 12 of 35 patients before introduction of the protocol, and in 10 of 51 patients after its introduction (p = 0.139). Donor-site local anaesthetic infusion reduces opioid requirements for patients undergoing head and neck free flap reconstruction, and is a valuable adjunct to an enhanced recovery protocol.

Inflexibility of the plasma miRNA response following a high-carbohydrate meal in overweight insulin-resistant women.

CONTEXT: Metabolic inflexibility is a characteristic of insulin resistance, limiting the ability to transiently regulate oxidative metabolism and gene expression in response to nutrient availability. Little is known of the flexibility of post-transcriptional regulation, including circulatory miRNAs (c-miRNAs). DESIGN: The abundances of targeted c-miRNAs, with reported functions in metabolic regulation, were analysed in response to a high-carbohydrate meal in healthy weight insulin-sensitive (IS) and overweight insulin-resistant (IR) women. PARTICIPANTS: Age-matched healthy weight IS (n = 20, BMI = 24.3 ± 0.70) and overweight IR (n = 20, BMI = 28.6 ± 0.67) women. METHODS: An abundance of c-miRNAs was quantified prior to and following a high-carbohydrate breakfast meal (2500 kJ; 50% carbohydrate, 20% fat and 27% protein). Target genes of the differentially regulated c-miRNA were measured in RNA extracted from circulatory peripheral blood mononuclear cells (PBMCs). RESULTS: In healthy weight IS women, both miR-15a-5p (p = 0.03) and miR-17-5p (p < 0.01) levels were halved at 4 h post-meal. These miRNA remained unaltered following the same meal in the overweight IR women. Furthermore, amongst genes targeted by these miRNA, CPT1A (p = 0.01) and IL8 (p = 0.03) had also reduced expression 4 h post-meal only in the healthy weight IS women. CONCLUSIONS: The study findings provide preliminary evidence for a possible extension of metabolic inflexibility to include c-miRNAs. TRIAL REGISTRATION: The clinical trial is registered with Australian New Zealand Clinical Trials Registry under Trial registration: ANZCTR: ACTRN12615001108505. Registered on 21 October 2015.

Brown fat activity determined by infrared thermography and thermogenesis measurement using whole body calorimetry (BRIGHT Study).

To assess BAT activity in humans at a population level, infrared thermography (IRT) represents a safe, readily repeatable and affordable alternative to 18F-FDG-PET. Building upon a previously proposed method by our laboratory, we further refined the image computational algorithm to quantify BAT activation in the cervical-supraclavicular (C-SCV) region of healthy young men under thermo-neutral and cold exposure conditions. Additionally, we validated the whole-body calorimeter (WBC) in reliably measuring cold-induced thermogenesis. The temperature gradient between C-SCV-deltoid regions, and the corresponding difference in heat power output, increased upon cold air exposure relative to thermo-neutral conditions (by 74.88 %, p<0.0001; and by 71.34 %, p<0.0001 respectively). Resting and cumulative energy expenditure (EE) rose significantly (by 13.14 % and 9.12 % respectively, p=0.0001) while positive correlations between IRT measures and EE were found with cold air exposure (percentage change in heat power gradient between ROI and deltoid, cold air: r(2)=0.29, p=0.026, Pearson's correlation). IRT and WBC can be used to study BAT activation. The refined algorithm allows for more automation and objectivity in IRT data analysis, especially under cold air exposures.

Body composition measurement in young children using quantitative magnetic resonance: a comparison with air displacement plethysmography.

BACKGROUND: Quantitative magnetic resonance (QMR) has been increasingly used to measure human body composition, but its use and validation in children is limited. OBJECTIVE: We compared body composition measurement by QMR and air displacement plethysmography (ADP) in preschool children from Singapore's multi-ethnic Asian population (n = 152; mean ± SD age: 5.0 ± 0.1 years). METHODS: Agreements between QMR-based and ADP-based fat mass and fat mass index (FMI) were assessed using intraclass correlation coefficient (ICC), reduced major axis regression and Bland-Altman plot analyses. Analyses were stratified for the child's sex. RESULTS: Substantial agreement was observed between QMR-based and ADP-based fat mass (ICC: 0.85) and FMI (ICC: 0.82). Reduced major axis regression analysis suggested that QMR measurements were generally lower than ADP measurements. Bland-Altman analysis similarly revealed that QMR-based fat mass were (mean difference [95% limits of agreement]) -0.5 (-2.1 to +1.1) kg lower than ADP-based fat mass and QMR-based FMI were -0.4 (-1.8 to +0.9) kg/m2 lower than ADP-based FMI. Stratification by offspring sex revealed better agreement of QMR and ADP measurements in girls than in boys. CONCLUSIONS: QMR-based fat mass and FMI showed substantial agreement with, but was generally lower than, ADP-based measures in young Asian children.

Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin.

BACKGROUND: Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans. HYPOTHESIS/OBJECTIVES: We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept. ANIMALS: Fourteen client-owned dogs were prospectively enrolled. METHODS: Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia. RESULTS: A 90-minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.

Fruit form Influences Postprandial Glycemic Response in Elderly and Young Adults.

OBJECTIVES: This study compared the effects of consuming different forms (bite size, puree) and two fruit types (guava, papaya) on glycemic response (GR) in elderly and young adults. DESIGN: This study was conducted using a randomized, crossover design. PARTICIPANTS: Nineteen healthy participants (9 elderly, 10 young adults) were recruited from the general public in Singapore. INTERVENTION: Participants consumed glucose (reference food) on three occasions and test fruits (guava bites, guava puree, papaya bites, and papaya puree) on one occasion each. MEASUREMENTS: Blood glucose was analyzed prior to consuming the test food, at 15, 30, 45, 60, 90 and 120 minutes after food consumption. RESULTS: The incremental area under the blood glucose response curve (iAUC) over 120 minutes for all the treatments was significantly lower than glucose (all P < 0.001). All fruit forms and types studied were low glycemic index (GI) (guava bites: 29; papaya bites: 38; papaya puree: 42; guava puree: 47), albeit a significant difference in GI between the treatments was found (P = 0.003). Elderly exhibited significantly greater GR than young participants (P = 0.019). CONCLUSION: Although fruit form influences GR in the elderly and young adults, all fruit types and forms studied were found to be low GI. This study indicates that fruits are a valuable source of nutrient irrespective of the form of delivery in elderly and young adults. This study was registered at www.anzctr.org.au as ACTRN12614000655640.

Even minimal polishing of an Indian parboiled brown rice variety leads to increased glycemic responses.

BACKGROUND AND OBJECTIVES: To evaluate the effect of polishing on the glycemic properties of Indian parboiled brown rice. METHODS AND STUDY DESIGN: We evaluated the effect of different degrees of polishing on the glycemic and insulinemic responses of Bapatla (BPT-5204), Indian parboiled Indica rice variety. Brown rice (BR), under milled rice (UMR) and white rice (WR) with 2.3% and 9.7% degree of polishing (DOP), respectively, were prepared and evaluated for the glycemic properties. Incremental Area Under the Curves (IAUC) were estimated for both glycemic index (GI) in 12 healthy participants (6 men, 6 women) and 24 hr glycemic response studies in 13 overweight participants (5 men, 8 women) using continuous glucose monitoring (CGM) system with ≈2000 kcal/day rice diets. Differences in pre and post meal insulin (Δ) were assessed. RESULTS: The GI of WR (GI=79.6) and UMR (GI=73) were significantly higher than BR (GI=57.6) (p<0.01). Similar results were obtained for 24 hr glycemic responses [IAUC: WR=58.4, UMR=55.5, BR=34.7 mg*5 min/dL, respectively]. The Δ Insulin responses were lower with BR meals compared with UMR and WR (p=0.025; p=0.003). CONCLUSIONS: Both UMR and WR had a high GI while BR had a medium GI. This could have influenced the 24 h glycaemic and insulinemic responses of BR which had the lowest responses as compared with UMR and WR, and the latter two had similar higher responses. Thus any degree of polishing leads to higher glycaemic responses.

Central adiposity-induced plasma-free amino acid alterations are associated with increased insulin resistance in healthy Singaporean adults.

BACKGROUND/OBJECTIVES: Recent metabolomics technique reveals a plasma-free amino acid (PFAA)-based metabolite signature that is suggestive of altered PFAAs being an early manifestation of obesity-related insulin resistance. However, the PFAA profiles within non-obese, but more insulin-resistant Asians are not well researched. Compared with Caucasians, Asian populations have more central adiposity, which is generally regarded as metabolically more adverse, but the underlying mechanisms remain unclear. In the present study, we examined whether PFAA profiling was at least one important factor mediating central adiposity and insulin resistance, and aid in cardiovascular risk assessment in healthy Asians with normal body weight. SUBJECT/METHODS: This was a cross-sectional study. A total of 190 healthy men (n=87 with a mean±s.d. body mass index (BMI) of 23.5±3.5 kg/m2) and women (n=103 with a mean±s.d. BMI of 21.4±3.7 kg/m2) residing in Singapore took part in this study. PFAA levels were measured by using an amino acid analyzer. Basic anthropometric measurements, fasting blood glucose, fasting serum insulin and lipid profiles were obtained using standard protocols. RESULTS: Seven out of 18 amino acids were significantly correlated with measures of obesity (for example, waist circumference; waist-to-hip ratio and BMI) in current participants. Among them, the plasma concentrations of five amino acids, including Phe, Tyr, Met, Ala and His were positively associated with waist-to-hip ratio. With the exception of His, which had no association with insulin resistance, Phe, Tyr, Met and Ala were significantly associated with hyperinsulinemia and insulin resistance (P<0.05). In contrast, no associations were observed between circulating BCAAs (that is, Val, Leu, Ile), measures of obesity and insulin resistance. However, significant inverse associations were observed between BCAAs and total cholesterol and high-density lipoprotein. CONCLUSIONS: We found that central adiposity was associated with alterations of specific amino acids. As a result, PFAAs may serve as metabolite predictors of hyperglycemia, hyperinsulinemia and dyslipidemia in healthy participants.

Effects of non-nutritive (artificial vs natural) sweeteners on 24-h glucose profiles.

Replacing nutritive sweetener with non-nutritive sweeteners (NNS) has the potential to improve glycaemic control. The objective of this study was to investigate the effects of consuming artificial NNS (that is, aspartame), natural NNS (that is, monk fruit and stevia), and sucrose-sweetened beverages on 24-h glucose profiles. Ten healthy males took part in this randomised, crossover study with the following four treatments: aspartame-, monk fruit-, stevia-, and sucrose- (65 g) sweetened beverages. Participants were asked to consume the test beverage as a preload mid-morning. Medtronic iPro2 continuous glucose monitoring system was used to measure mean 24-h glucose, incremental area under the curve (iAUC) and total area under the curve (AUC) for glucose, and 24-h glycaemic variability. Overall no significant differences were found in mean 24-h glucose, iAUC and total AUC for glucose, and 24-h glycaemic variability between the four test beverages. Twenty-four-hour glucose profiles did not differ between beverages sweetened with non-nutritive (artificial vs natural) and nutritive sweeteners. The simple exchange of a single serving of sucrose-sweetened beverage with NNS over a day appears to have minimal effect on 24-h glucose profiles in healthy males.

Plasma-free amino acid profiles are predictors of cancer and diabetes development.

Type 2 diabetes (T2D) and cancers are two major causes of morbidity and mortality worldwide. Nowadays, there is convincing evidence of positive associations between T2D and the incidence or prognosis of a wide spectrum of cancers, for example, breast, colon, liver and pancreas. Many observational studies suggest that certain medications used to treat hyperglycemia (or T2D) may affect cancer cells directly or indirectly. The potential mechanisms of the direct T2D cancer links have been hypothesized to be hyperinsulinemia, hyperglycemia and chronic inflammation; however, the metabolic pathways that lead to T2D and cancers still remain elusive. Plasma-free amino acid (PFAA) profiles have been highlighted in their associations with the risks of developing T2D and cancers in individuals with different ethnic groups and degree of obesity. The alterations of PFAAs might be predominately caused by the metabolic shift resulted from insulin resistance. The underlying mechanisms have not been fully elucidated, in particular whether the amino acids are contributing to these diseases development in a causal manner. This review addresses the molecular and clinical associations between PFAA alterations and both T2D and cancers, and interprets possible mechanisms involved. Revealing these interactions and mechanisms may improve our understanding of the complex pathogenesis of diabetes and cancers and improve their treatment strategies.

Dynamics affecting the risk of silent circulation when oral polio vaccination is stopped.

Waning immunity could allow transmission of polioviruses without causing poliomyelitis by promoting silent circulation (SC). Undetected SC when oral polio vaccine (OPV) use is stopped could cause difficult to control epidemics. Little is known about waning. To develop theory about what generates SC, we modeled a range of waning patterns. We varied both OPV and wild polio virus (WPV) transmissibility, the time from beginning vaccination to reaching low polio levels, and the infection to paralysis ratio (IPR). There was longer SC when waning continued over time rather than stopping after a few years, when WPV transmissibility was higher or OPV transmissibility was lower, and when the IPR was higher. These interacted in a way that makes recent emergence of prolonged SC a possibility. As the time to reach low infection levels increased, vaccine rates needed to eliminate polio increased and a threshold was passed where prolonged low-level SC emerged. These phenomena were caused by increased contributions to the force of infection from reinfections. The resulting SC occurs at low levels that would be difficult to detect using environmental surveillance. For all waning patterns, modest levels of vaccination of adults shortened SC. Previous modeling studies may have missed these phenomena because (1) they used models with no or very short duration waning and (2) they fit models to paralytic polio case counts. Our analyses show that polio case counts cannot predict SC because nearly identical polio case count patterns can be generated by a range of waning patterns that generate different patterns of SC. We conclude that the possibility of prolonged SC is real but unquantified, that vaccinating modest fractions of adults could reduce SC risk, and that joint analysis of acute flaccid paralysis and environmental surveillance data can help assess SC risks and ensure low risks before stopping OPV.

Programmed death ligand 1 is expressed in canine B cell lymphoma and downregulated by MEK inhibitors.

Programmed death ligand 1 (PD-L1) expression in antigen-presenting cells and tumors can inhibit T cell-mediated immunity. In this study, PD-L1 mRNA and protein expression was evaluated in canine B cell lymphoma (CLL17-71), large T-cell leukemia (CLGL-90), B cell leukemia (GL-1) and primitive leukocyte round cell neoplasia (CLL-1390). Variable PD-L1 mRNA and protein were observed in these cells with high endogenous expression present in CLL17-71 cells. PD-L1 protein was also observed in canine patient B cell lymphoma tissues using immunostaining. PD-L1 and signal transducer and activator of transcription 1 ( STAT1 ) mRNA expression were reduced in the presence of mitogen-activated protein kinase kinase 1.2 (MEK1/2) inhibitors RDEA119 and AZD6244 in CLL 17-71 cells. RDEA119 had similar effect on PD-L1 and STAT-1 in IFN-γ activated CLL-1390 cells. Overall, these results indicate that PD-L1 is expressed in canine B cell lymphoma. Its inhibition by MEK1/2 inhibitors suggests a possible treatment strategy using targeted drugs which likely could enhance antitumor immune response.

Gross and relative energy cost of domestic household activities in Asian men.

BACKGROUND/OBJECTIVES: Obesity is on the rise and participation in exercise has declined. Domestic household activities may help meet the recommended daily physical activity levels. This study aimed to measure the energy costs of household activities among Asian males. SUBJECTS/METHODS: This was a randomised cross-over study conducted in a whole-body calorimeter. The energy costs of 14 domestic household activities, divided into two studies, were measured in 10 healthy Asian males. Participants' weight, height, body composition and basal metabolic rate were measured on the first test visit. A standard breakfast was served and participants rested for an hour before the measurement of energy costs of domestic household activities. During the measurements, each activity was performed for 20 min, and participants rested for 30 min between activities. RESULTS: The mean energy costs of domestic household activities ranged from 5.92 to 11.97 kJ/min, which were significantly different between activities (repeated measures analysis of variance, P<0.001). When expressed as metabolic equivalents (METS), all domestic household activities were classified as low-intensity physical activities. Actual METS (METSactual) were significantly different to standard METS of eight activities, which may be partly explained by the universal assumption of 3.5 ml O2/kg/min made during the calculation of METS in the Asian population. CONCLUSIONS: The energy costs of a range of domestic household activities reported in this study may assist in the planning of physical activities among Asians to meet national physical activity guidelines.

Aerial Mobile Radiation Survey Following Detonation of a Radiological Dispersal Device.

A series of experiments was conducted in 2012 at the Defence Research and Development Canada's Suffield Research Centre in Alberta, Canada, during which three radiological dispersal devices were detonated. The detonations released radioactive (140)La into the air, which was then carried by winds and detectable over distances of up to 2 km. The Nuclear Emergency Response group of Natural Resources Canada conducted airborne radiometric surveys shortly following the explosions to map the pattern of radioactivity deposited on the ground. The survey instrument suite was based on large volume NaI(Tl) scintillation gamma radiation detectors, which were situated in a basket mounted exterior to the helicopter and oriented end-to-end to maximize the sensitivity. A standard geophysical data treatment was used to subtract backgrounds and to correct the data to produce counts due to (140)La at the nominal altitude. Sensitivity conversion factors obtained from Monte Carlo simulations were then applied to express the measurements in terms of surface activity concentration in kBq m(-2). Integrated over the survey area, the results indicate that only 20 to 25% of the bomb's original inventory of radioactive material is deposited within a 1.5-km radius of ground zero. These results can be accommodated with a simple model for the RDD behavior and atmospheric dispersion.

Comparison of transforming growth factor beta expression in healthy and diseased human tendon.

BACKGROUND: Diseased tendons are characterised by fibrotic scar tissue, which adversely affects tendon structure and function and increases the likelihood of re-injury. The mechanisms and expression profiles of fibrosis in diseased tendon is understudied compared to pulmonary and renal tissues, where transforming growth factor (TGF)ß and its associated superfamily are known to be key drivers of fibrosis and modulate extracellular matrix homeostasis. We hypothesised that differential expression of TGFß superfamily members would exist between samples of human rotator cuff tendons with established disease compared to healthy control tendons. METHODS: Healthy and diseased rotator cuff tendons were collected from patients presenting to an orthopaedic referral centre. Diseased tendinopathic (intact) and healthy rotator cuff tendons were collected via ultrasound-guided biopsy and torn tendons were collected during routine surgical debridement. Immunohistochemistry and quantitative real-time polymerase chain reaction were used to investigate the protein and gene expression profiles of TGFß superfamily members in these healthy and diseased tendons. RESULTS: TGFß superfamily members were dysregulated in diseased compared to healthy tendons. Specifically, TGFß-1, TGFß receptor (R)1 and TGFß R2 proteins were reduced (p < 0.01) in diseased compared to healthy tendons. At the mRNA level, TGFß R1 was significantly reduced in samples of diseased tendons, whereas TGFß R2 was increased (p < 0.01). BMP-2, BMP-7 and CTGF mRNA remained unchanged with tendon disease. CONCLUSIONS: We propose that downregulation of TGFß pathways in established tendon disease may be a protective response to limit disease-associated fibrosis. The disruption of the TGFß axis with disease suggests associated downstream pathways may be important for maintaining healthy tendon homeostasis. The findings from our study suggest that patients with established tendon disease would be unlikely to benefit from therapeutic TGFß blockade, which has been investigated as a treatment strategy in several animal models. Future studies should investigate the expression profile of fibrotic mediators in earlier stages of tendon disease to improve understanding of the targetable mechanisms underpinning tendon fibrosis.