Comparative Toxicity of Seven Aqueous Film-Forming Foam to In Vitro Systems and Mus.

The comparative toxicity of six per- and polyfluoroalkyl substance (PFAS)-free and one PFAS-containing aqueous film-forming foam (AFFF) was evaluated in an outbred mouse species as well as several in vitro assays. The in vivo toxicological profile of PFAS-free AFFFs in short-term, high-concentration exposures is different than that of a PFAS-containing AFFF. The PFAS-containing reference product induced increased liver weights, while the PFAS-free AFFFs were linked to either decreased or unaffected relative liver weights. The in vitro toxicological profile across PFAS-free AFFFs was uniform except in the Microtox® assay, where thresholds were variable and spanned several orders of magnitude. This direct comparison of products through short-term toxicity tests and in vitro screenings represents early data to support evaluation of potential regrettable substitutions when selecting alternative PFAS-free AFFFs. Further work in diverse taxa (e.g., aquatic organisms, terrestrial invertebrates, birds) and mammalian studies capturing sensitive life stages will refine and expand this data set across a range of risk-relevant toxicological endpoints. Environ Toxicol Chem 2023;42:2364-2374. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Integrating "One Health" Concepts in the Design of Sustainable Systems for Environmental Use.

Ensuring for the national defense requires the use of substances such as energetics, propellants, pyrotechnics, and other materials in environmental applications. Systems that use these materials do so in testing and training environments and must be used in an environmentally sustained manner to ensure success during actual kinetic defensive operations. Environmental and occupational health assessments require a weighted evaluation of toxicity, bioaccumulation, persistence, and environmental fate and transport considerations for each substance in the formulation to include potential combustion products. Data that support these criteria need to be collected in a phased and matrixed approach and considered iteratively as technology advances. Further, these criteria are often considered as disparate and separate; hence, comparing favorable aspects of one may or may not offset detrimental data from another. Here, we describe an approach to the phased collection of environmental, safety, and occupational health (ESOH) information for new systems and substances and provide recommendations for evaluating such data streams in making decisions for use and for evaluating alternatives.

Randomised, cOntrolled Multicentre trial of 26 weeks subcutaneous liraglutide (a glucagon-like peptide-1 receptor Agonist), with or without contiNuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoEa (OSA) (ROMANCE): study protocol assessing the effects of weight loss on the apnea-hypnoea index (AHI).

INTRODUCTION: Obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) often occur concurrently, and untreated OSA may potentially amplify the high risk of cardiovascular disease in T2DM. Compliance with continuous positive airway pressure (CPAP), the conventional treatment for OSA, can be poor and considering weight loss is the most effective treatment for OSA. This trial examines whether the glucagon-like peptide-1 receptor agonist liraglutide, a glucose-lowering therapy associated with significant weight loss used in T2DM, can improve the severity and symptoms of OSA. METHODS AND ANALYSIS: This is an outpatient, single-centred, open-labelled, prospective, phase IV randomised controlled trial in a two-by-two factorial design. One hundred and thirty-two patients with newly diagnosed OSA (apnoea-hypopnoea index (AHI) ≥15 events/hour), and existing obesity and T2DM (glycated haemoglobin (HbA1c) ≥47 mmol/mol), will be recruited from diabetes and sleep medicine outpatient clinics in primary and secondary care settings across Liverpool. Patients will be allocated equally, using computer-generated random, permuted blocks of unequal sizes, to each of the four treatment arms for 26 weeks: (i) liraglutide (1.8 mg once per day) alone, (ii) liraglutide 1.8 mg once per day with CPAP, (iii) CPAP alone (conventional care) or (iv) no treatment (control). The primary outcome measure is change in OSA severity, determined by AHI. Secondary outcome measures include effects on glycaemic control (glycated haemoglobin (HbA1c)), body weight and quality of life measures. Exploratory measures include measures of physical activity, MRI-derived measures of regional body composition including fat mass (abdominal subcutaneous, visceral, neck and liver fat) and skeletal muscle mass (cross-sectional analysis of thigh), indices of cardiac function (using transthoracic echocardiography) and endothelial function. ETHICAL APPROVAL: The study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1019) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBERS: ISRCTN16250774. EUDRACT No. 2014-000988-41. UTN U1111-1139-0677.

In vitro and in vivo effects of 5-aminotetrazole (5-AT), an energetic compound.

Perchlorate is an important oxidizer used in propellants, pyrotechnics, and as a gas generator in commercial airbags, fireworks, and roadside flares. It is highly water soluble, interferes with thyroidal iodide uptake and is an environmental contaminant. By changing the reaction chemistry, 5-aminotetrazole (5-AT) and nitrates replace perchlorate in some propellants. The short term toxicity of 5-AT was evaluated. Using a modified Ames assay, 5-AT was not mutagenic with or without S9 metabolic activation. 5-AT was considered "slightly toxic" with an EC50 of 28.8 mg 5-AT/L for a 15 min exposure in Aliivibrio fischeri. In the in vitro sodium iodide symporter test, 5-AT did not inhibit the uptake of iodine. In the acute rat oral test, no adverse effects and no mortalities were observed at the limit dose of 2000 mg 5-AT/kg. In the 14-day sub-acute study, there were no clinical signs of toxicity or morbidity up to 623 mg 5-AT/kg-day; the highest dose tested. No differences were observed in hematology, clinical chemistry, organ weight, body weight, food consumption, histopathology, or DNA damage (peripheral blood micronucleus assay) of treatments compared with controls. The No Observed Adverse Effect Level (NOAEL) was 623 mg 5-AT/kg-day, the highest dose in the subacute oral bioassay.

Resting-state functional brain networks in adults with a new diagnosis of focal epilepsy.

OBJECTIVES: Newly diagnosed focal epilepsy (NDfE) is rarely studied, particularly using advanced neuroimaging techniques. Many patients with NDfE experience cognitive impairments, particularly with respect to memory, sustained attention, mental flexibility, and executive functioning. Cognitive impairments have been related to alterations in resting-state functional brain networks in patients with neurological disorders. In the present study, we investigated whether patients with NDfE had altered connectivity in large-scale functional networks using resting-state functional MRI. METHODS: We recruited 27 adults with NDfE and 36 age- and sex-matched healthy controls. Resting-state functional MRI was analyzed using the Functional Connectivity Toolbox (CONN). We investigate reproducibly determined large-scale functional networks, including the default mode, salience, fronto-parietal attention, sensorimotor, and language networks using a seed-based approach. Network comparisons between patients and controls were thresholded using a FDR cluster-level correction approach. RESULTS: We found no significant differences in functional connectivity between seeds within the default mode, salience, sensorimotor, and language networks and other regions of the brain between patients and controls. However, patients with NDfE had significantly reduced connectivity between intraparietal seeds within the fronto-parietal attention network and predominantly frontal and temporal cortical regions relative to controls; this finding was demonstrated including and excluding the patients with brain lesions. No common alteration in brain structure was observed in patients using voxel-based morphometry. Findings were not influenced by treatment outcome at 1 year. CONCLUSIONS: Patients with focal epilepsy have brain functional connectivity alterations at diagnosis. Functional brain abnormalities are not necessarily a consequence of the chronicity of epilepsy and are present when seizures first emerge.

Effects of a Group-Based Behavioral Intervention on Dietary Behaviors in Older Adults.

OBJECTIVE: The aim of this study is to examine the effects of a 12-week, behavioral nutrition intervention on dietary behaviors. METHOD: Inactive older adults ( N = 50) were randomized to a 12-week, behavioral nutrition or physical activity intervention, delivered in a group-based format. Questionnaires assessed fruit and vegetable (FV) consumption, and fat- and fiber-related behaviors at baseline and postintervention. Height and weight were measured. Repeated-measures ANOVAs examined changes in dietary behaviors over time between groups, controlling for age, gender, and education. RESULTS: Participants averaged 64.1 ± 8.4 years of age and had a body mass index (BMI) of 33.3 ± 7.5 kg/m2. Group × Time interactions were significant for FV consumption ( p = .003), and fat- ( p = .02) and fiber-related ( p = .008) behaviors at 12 weeks. At 12 weeks, dietary behaviors improved significantly in the nutrition but not in the physical activity group. Effect sizes were medium to large. DISCUSSION: A 12-week, behavioral nutrition intervention improved dietary behaviors. Behavioral interventions may be a low-cost way to improve dietary behaviors among older adults, potentially affecting population health significantly.

Implementation of the basic hazard index screening for health risks associated with simultaneous exposure to multiple chemicals using a standardized target organ and systems framework.

Environmental health risk assessments often involve assessing the potential health effects of exposure to multiple chemicals at once (i.e., complex mixtures). Because the possible number of chemical combinations is very large, few controlled in vivo toxicological studies with chemical mixtures are relevant or practical. In lieu of specific mixture toxicity data, the segregated hazard index (HI) approach has been used to determine whether simultaneous exposures may warrant further investigation due to their combined adverse effects. Each chemical is assigned to one or more target organs based on critical effects; HIs for each target organ are generated by summing the individual hazard quotients for each of the chemicals assigned to that organ or organ system. To conduct this phased risk assessment approach in a consistent manner, a comprehensive, systematized list of toxicity targets for implementing this approach is needed. We present a comprehensive and standardized list of toxicity target organs and systems (TTOS), with example data sets, for consistent implementation of the segregated HI method. This method is designed to facilitate the standardization of the widespread use of the basic segregated HI approach. The basic hazard index mixtures screening (BHIMS) tool allows for rapid identification of exposure concerns that may warrant further and more sophisticated assessment. Integr Environ Assess Manag 2017;13:852-860. Published 2017. This article is a US Government work and is in the public domain in the USA.

Perceptions of body weight and nutritional practices among male and female National Collegiate Athletic Association Division II athletes.

OBJECTIVE: This study investigated body weight and nutritional behavior perceptions among Division II collegiate athletes. PARTICIPANTS: The sample was composed of 155 collegiate athletes who responded to a survey. METHODS: Data were self-reported by athletes via questionnaire. Independent-sample t tests were used to identify significant gender differences related to body weight perceptions, nutritional practices, and ideal weight difference (IWD). An alpha level of .05 was used to determine statistical significance. RESULTS: Mean ± SD female and male IWD was -6.8 ± 8.8 and 1.3 ± 12.3 lbs, respectively (p < .001). Significant differences in level of agreement regarding perceived body weight effects on performance and dietary practices existed between genders. CONCLUSIONS: Significant gender differences may exist regarding body weight perceptions and nutritional practices among collegiate athletes. Deliverance of gender-specific educational information about proper nutritional practices is warranted. To properly tailor interventions to specific sports, research with larger sample sizes is needed.

Reliability of measurements of tongue and hand strength and endurance using the Iowa Oral Performance Instrument with elderly adults.

PURPOSE: This study investigated the reliability of tongue and hand strength and endurance measurements in old adults using the Iowa Oral Performance Instrument (IOPI). METHOD: Thirty aged-care residents (6 males and 24 females) aged 79-97 years were tested on four occasions two weeks apart to determine test-retest reliability. The primary outcome measures were isometric anterior and posterior tongue and hand strength (best of three trials) and isometric tongue and hand endurance time at 50% of maximal strength. RESULTS: Changes in the mean between sessions for tongue and hand strength indicated acceptable (< 10%) reliability particularly with familiarisation. The within-subject variation (mean-typical error expressed as a coefficient of variation, CV) indicated higher than acceptable variation for anterior and posterior tongue and hand strength. Intra-class correlations (ICC) indicated moderate to strong reliability for anterior (ICC 0.58-0.77) and posterior (ICC 0.77-0.84) tongue strength and hand strength (ICC 0.79-0.96). No tongue or hand endurance measures were regarded as reliable. CONCLUSION: These findings indicate that overall tongue and hand strength values demonstrate acceptable reliability in the elderly, especially where familiarisation with the IOPI is provided. Further investigation to reduce sources of variability in tongue endurance measurements is warranted.

The role of emotional vulnerability and abuse in the financial exploitation of older people from culturally and linguistically diverse communities in Australia.

While the literature acknowledges that older people from culturally and linguistically diverse (CaLD) communities are particularly susceptible to financial abuse by their family members, there is a dearth of research that explores the nature of CaLD older people's vulnerability to this form of abuse. This case study examines unique dynamics shaping this form of abuse and demonstrates how emotional vulnerability and dependence, exacerbated by cultural and linguistic disconnection, can place older people at risk.

The effect of neoadjuvant chemoradiotherapy on whole-body physical fitness and skeletal muscle mitochondrial oxidative phosphorylation in vivo in locally advanced rectal cancer patients--an observational pilot study.

BACKGROUND: In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness. METHODS: We prospectively studied 12 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy, recruited from a large tertiary cancer centre, between October 2012 and July 2013. All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy. Data were analysed and reported blind to patient identity and clinical course. Primary variables of interest were the two physical fitness measures; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise (ml.kg-1.min-1), and the post-exercise phosphocreatine recovery rate constant (min-1), a measure of muscle mitochondrial capacity in vivo. RESULTS: Median age was 67 years (IQR 64-75). Differences (95%CI) in all three primary variables were significantly negative post-NACRT: Oxygen uptake at estimated anaerobic threshold -2.4 ml.kg-1.min-1 (-3.8, -0.9), p = 0.004; Oxygen uptake at Peak -4.0 ml.kg-1.min-1 (-6.8, -1.1), p = 0.011; and post-exercise phosphocreatine recovery rate constant -0.34 min-1 (-0.51, -0.17), p<0.001. CONCLUSION: The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms, no doubt multifactorial, may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy. This may have implications for targeted interventions to improve physical fitness pre-surgery. TRIAL REGISTRATION: Clinicaltrials.gov registration NCT01859442.

Financial abuse of older people by a family member: a difficult terrain for service providers in Australia.

Financial abuse by a family member is the most common form of abuse experienced by older Australians, and early intervention is required. National online surveys of 228 chief executive officers and 214 aged care service providers found that, while they were well placed to recognize financial abuse, it was often difficult to intervene successfully. Problems providers encountered included difficulties in detecting abuse, the need for consent before they could take action, the risk that the abusive family member would withdraw the client from the service, and a lack of resources to deal with the complexities inherent in situations of financial abuse.

Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle.

Non-alcoholic fatty liver disease (NAFLD), characterized by lipid deposition within the liver [intrahepatocellular lipid (IHCL)], is associated with insulin resistance and the metabolic syndrome (MS). It has been suggested that impaired skeletal muscle mitochondrial function may contribute to ectopic lipid deposition, and the associated MS, by altering post-prandial energy storage. To test this hypothesis, we performed a cross-sectional study of 17 patients with NAFLD [mean±S.D.; age, 45±11 years; body mass index (BMI), 31.6±3.4 kg/m2] and 18 age- and BMI-matched healthy controls (age, 44±11 years; BMI, 30.5±5.2 kg/m2). We determined body composition by MRI, IHCL and intramyocellular (soleus and tibialis anterior) lipids (IMCLs) by proton magnetic resonance spectroscopy (1H-MRS) and skeletal muscle mitochondrial function by dynamic phosphorus magnetic resonance spectroscopy (31P-MRS) of quadriceps muscle. Although matched for BMI and total adiposity, after statistical adjustment for gender, patients with NAFLD (defined by IHCL ≥ 5.5%) had higher IHCLs (25±16% compared with 2±2%; P<0.0005) and a higher prevalence of the MS (76% compared with 28%) compared with healthy controls. Despite this, the visceral fat/subcutaneous fat ratio, IMCLs and muscle mitochondrial function were similar between the NAFLD and control groups, with no significant difference in the rate constants of post-exercise phosphocreatine (PCr) recovery (1.55±0.4 compared with 1.51±0.4 min-1), a measure of muscle mitochondrial function. In conclusion, impaired muscle mitochondrial function does not seem to underlie ectopic lipid deposition, or the accompanying features of the MS, in patients with NAFLD.

Reliability of measurements of tongue and hand strength and endurance using the Iowa Oral Performance Instrument with healthy adults.

The purpose of this study was to investigate the reliability of tongue and handgrip strength and endurance measurements in healthy adults using the Iowa Oral Performance Instrument. Fifty-one healthy participants (21 males, 30 females; age range = 19-57 years) were tested on four occasions 1 week apart to determine test-retest reliability. The primary outcome measures were isometric tongue and handgrip strength (best of three trials) and sustained isometric endurance. Small increases (changes in group mean) in both anterior (1.7 %) and posterior (2.5 %) tongue strength and handgrip strength (5 %) between weeks 1 and 2 were observed with no change in subsequent weeks, suggesting that there is only a small learning effect for these measurements. The within-subject variation (mean-typical error expressed as a coefficient of variation [CV]) indicated higher than desirable initial variation for anterior (CV 10.8 %) and posterior (CV 11.8 %) tongue strength and handgrip strength (CV 15.2 %) but this was reduced in weeks 2-4. Intraclass correlation coefficients (ICC) indicated acceptable and improved reliability for both anterior (ICC 0.77-0.90) and posterior (ICC 0.79-0.86) tongue strength and handgrip strength (ICC 0.69-0.91) after week 1. Additional exploratory analyses were conducted with a subset of data to determine whether two values within 5 kPa (tongue) or 15 kPa (handgrip) provide superior strength reliability. Neither tongue nor hand endurance measurements were sufficiently reliable. These findings suggest that tongue and handgrip strength values demonstrate acceptable reliability, especially if familiarization is provided. Further investigation is needed to reduce sources of variability in tongue endurance measurements.

A systematic review and meta-analysis of measurements of tongue and hand strength and endurance using the Iowa Oral Performance Instrument (IOPI).

The purpose of this systematic review was to examine the evidence for the use of the Iowa Oral Performance Instrument (IOPI) to measure strength and endurance of the tongue and hand in healthy populations and those with medical conditions. A systematic search of the scientific literature published since 1991 yielded 38 studies that addressed this purpose. The IOPI was used primarily for tongue strength (38 studies) and endurance (15 studies) measurement; relatively few studies measured hand strength (9 studies) or endurance (6 studies). The majority of the studies identified used the IOPI as an evaluation tool, although four used it as an intervention tool. Half the studies were conducted in healthy people, primarily adults. Most of the other participants had disorders with dysphagia, primarily Parkinson's disease or head or neck cancer. Age and gender, as well as a number of medical conditions, influence the values of tongue and hand strength. There is sufficient evidence to support the use of the IOPI as a suitable tool for measuring tongue strength and endurance and as an assessment tool for intervention studies, and there is growing support for its use to assess hand strength and endurance in healthy and clinical populations.

Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months' GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA(1)c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT). We prospectively studied 25 (12 male) patients, age 50±10 years, BMI 38.4±5.6 kg/m(2) (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA(1)c of 9.6% (7.9 to 10.7%) (median and interquartile range). Patients treated with metformin and sulphonylureas/DPP-IV inhibitors were given 6 months GLP-1 RA (exenatide, n = 19; liraglutide, n = 6). IHL was quantified by liver proton magnetic resonance spectroscopy ((1)H MRS) and VAT and SAT by whole body magnetic resonance imaging (MRI). Treatment was associated with mean weight loss of 5.0 kg (95% CI 3.5,6.5 kg), mean HbA(1c) reduction of 1·6% (17 mmol/mol) (0·8,2·4%) and a 42% relative reduction in IHL (-59.3, -16.5%). The relative reduction in IHL correlated with that in HbA(1)c (ρ = 0.49; p = 0.01) but was not significantly correlated with that in total body weight, VAT or SAT. The greatest IHL reduction occurred in individuals with highest pre-treatment levels. Mechanistic studies are needed to determine potential direct effects of GLP-1 RA on human liver lipid metabolism.

Toxicologic characterization of a novel explosive, guanidinium 3,4-dinitropyrazolate (GDNP), in female rats and Ames mutagenicity assay.

Sustainable use of military training ranges requires the development of compounds that have a minimal impact to the environment when used in a weapon system. Guanidinium 3,4-dinitropyrazolate (GDNP) is a novel explosive compound of interest for application in some weapon systems. Little is known of its toxicologic properties. To ensure the health of potentially exposed personnel and the environment, initial toxicity investigations were conducted and the results were compared with another widely used energetic (hexahydro-1,3,5-trinitro-1,3,5-triazine [RDX]). In a microplate Ames assay, GDNP was not cytotoxic to bacterial tester strains at concentrations less than 100 µg/mL. However, GDNP was mutagenic to 4 of 5 bacterial strains with and without S9 metabolic incubation at concentrations as low as 0.7 µg/mL. Unlike RDX, GDNP did not have an affinity for the γ-aminobutyric acid(A) receptor convulsant site and was predicted to not induce seizure. After acute oral dosing in female rats, the median lethal dose in female rats of GDNP in tap water solution was determined to be 720 mg/kg. Daily oral exposure to 500 mg/kg per d of GDNP for 14 days caused weight loss, increased liver and spleen weights, and adverse histopathologic events in kidney and spleen. These adverse events were not observed in animals receiving lower doses of GDNP. In this study, the lowest-observed-adverse-effect-level from oral exposure to GDNP for 14 days was 500 mg/kg per d and the no-observable-adverse-effect-level was 152 mg/kg per d.

Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance.

CONTEXT: Nonalcoholic fatty liver disease may be evident in women with polycystic ovary syndrome (PCOS), both conditions being associated with obesity and insulin resistance. However, few studies have accounted for the high prevalence of obesity in PCOS. OBJECTIVE: The aim of this study was to determine whether PCOS is independently associated with hepatic steatosis, compared with healthy controls of similar age and body mass index (BMI), and whether steatosis is associated with hyperandrogenemia. DESIGN AND SETTING: We conducted a cross-sectional, case-control study at two tertiary referral centers. PATIENTS: Twenty-nine women with PCOS diagnosed by the Rotterdam criteria [aged 28 yr; 95% confidence interval (CI), 26-31; BMI, 33 kg/m2; 95% CI, 31-36] and 22 healthy controls (aged 29 yr; 95% CI, 28-31; BMI, 30 kg/m2; 95% CI, 28-33) were studied. METHODS: Proton-magnetic resonance spectroscopy quantified hepatic and skeletal muscle fat; whole body magnetic resonance imaging quantified internal, visceral, and sc adipose tissue volumes. Differences were assessed between PCOS and controls using t tests, and between hyperandrogenic (HA) PCOS, PCOS with normal androgens (NA), and controls using analysis of covariance. RESULTS: After statistical adjustment for BMI, HA-PCOS had significantly higher liver fat vs. NA-PCOS (3.7%; 95% CI, 0.6-13.1) and vs. controls (2.1%; 95% CI, 0.3-6.6). Similarly, after adjustment for homeostasis model assessment for insulin resistance, internal and visceral adipose tissue volumes, liver fat remained significantly greater in HA-PCOS compared to NA-PCOS and controls. CONCLUSION: These data suggest that HA-PCOS is associated with hepatic steatosis, independent of obesity and insulin resistance.

Hepatic steatosis, GH deficiency and the effects of GH replacement: a Liverpool magnetic resonance spectroscopy study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is reported to be more common in patients with GH deficiency (GHD) than in the general population. we aimed to determine: i) liver fat in patients with GHD compared with age and body mass index (BMI)-matched controls; and ii) effect of 6 months of GH replacement (GHR) on liver fat. PARTICIPANTS AND METHODS: The study included 28 GHD patients and 24 controls. 12 patients were studied before and after 6 months of GHR. Anthropometry, liver enzymes and lipid profiles were measured, and body composition and intrahepatocellular lipid (IHCL) were determined by magnetic resonance imaging and spectroscopy. RESULTS: Age and BMI (median (inter-quartile range)) of patients and controls were 52.6 (14) vs 52.6 (12) years (P=0.9) and 27.8 (24.7, 34.7) vs 27.9 (25.1, 32.1) kg/m(2) (P=0.9). IGF1 was lower in the patients (11.5 vs 16.0 nmol/l, P=0.002). There was no difference in liver transaminases, lipids or IHCL between patients and controls (2.8 (1.3, 8.6) vs 5.0 (1.5, 12.7), P=0.72), despite significantly higher visceral fat in GHD patients. Thirty-two percent of patients and 50% of controls had NAFLD (defined as IHCL >5.6%), and the relationship between IHCL and BMI was the same in each group. GHR significantly reduced abdominal subcutaneous and visceral fat in all patients; however, GHR did not reduce liver fat. CONCLUSIONS: NAFLD is equally common in patients with GHD and matched controls. GHR is associated with a hierarchical reduction in fat deposition (fat loss: visceral > subcutaneous > liver). Further studies involving GHD patients with NAFLD are required to conclude the role of GHR in treating NAFLD.