The advantages of physical exercise as a preventive strategy against NAFLD in postmenopausal women.

BACKGROUND: The prevalence and severity of nonalcoholic fatty liver disease (NAFLD) increase in women after menopause. This narrative review discusses the causes and consequences of NAFLD in postmenopausal women and describes how physical activity can contribute to its prevention. METHODS: The authors followed the narrative review method to perform a critical and objective analysis of the current knowledge on the topic. The Medical Subject Heading keywords 'physical exercise', 'menopause', 'hormone replacement therapy', 'estradiol' and 'NAFLD' were used to establish a conceptual framework. The databases used to collect relevant references included Medline and specialized high-impact journals. RESULTS: Higher visceral adiposity, higher rate of lipolysis in adipose tissue after oestrogen drop and changes in the expression of housekeeping proteins involved in hepatic lipid management are observed in women after menopause, contributing to NAFLD. Excessive liver steatosis leads to hepatic insulin resistance, oxidative stress and inflammation, accelerating NAFLD progression. Physical activity brings beneficial effects against several postmenopausal-associated complications, including NAFLD progression. Aerobic and resistance exercises partially counteract alterations induced by metabolic syndrome in sedentary postmenopausal women, impacting NAFLD progression and severity. CONCLUSIONS: With the increased global obesity epidemic in developing countries, NAFLD is becoming a severe problem with increased prevalence in women after menopause. Evidence shows that physical activity may delay NAFLD development and severity in postmenopausal women, although the prescription of age-appropriate physical activity programmes is advisable to assure the health benefits.

Multiplying effects of COVID-19 lockdown on metabolic risk and fatty liver.

BACKGROUND: Social containment measures imposed in Europe during the lockdown to face COVID-19 pandemic can generate long-term potential threats for metabolic health. METHODS: A cohort of 494 non-COVID-19 subjects living in 21 EU countries were interviewed by an anonymous questionnaire exploring anthropometric and lifestyle changes during 1-month lockdown. A subgroup of 41 overweight/obese Italian subjects with previously diagnosed nonalcoholic fatty liver (NAFLD) joined the study following a 12-month follow-up period promoting weight loss by healthy lifestyle. RESULTS: During the lockdown, body weight increased in 55% of subjects (average 2.4 ± 0.9 kg). Weight change increased with age, but not baseline body mass index. Subjects living in Italy had greater weight gain than those living in other European Countries. Weight gain during the lockdown was highest in subjects reporting no physical activity, and low adherence to Mediterranean diet. In the NAFLD group, weight gain occurred in 70% of cases. Subjects reporting weight loss during lockdown had decreased fatty liver score at 3 months before the lockdown, as compared with 1 year before. CONCLUSIONS: Strict measures of social containment-even short-term-pave the way to the increased risk of metabolic abnormalities in the medium-long term. In this context, adherence to Mediterranean diet and regular physical activity play a protective role both in terms of weight gain and fatty liver development/progression, with implication for primary and secondary prevention. When adopting measures imposing social containment, intensive educational campaigns must increase public awareness about beneficial effects of healthy lifestyles.

Household fuel mixes in peri-urban and rural Ecuador: Explaining the context of LPG, patterns of continued firewood use, and the challenges of induction cooking.

Nationwide transitions from cooking with solid fuels to clean fuels promise substantial health, climate, and environmental benefits. For decades, Ecuador has invested heavily in consumption subsidies for liquified petroleum gas (LPG), a leading clean fuel. With the goal of understanding household energy use in a context where LPG is ubiquitous and cheap, we administered 808 household surveys in peri-urban and rural communities in Coastal and Andean Ecuadorian provinces. We assess cooking fuel patterns after long-term LPG access and the reach of induction stoves promoted through a recent government program. Nearly all participants reported using LPG for more than a decade and frequent, convenient access to highly subsidized LPG. Nonetheless, half of rural households and 20% of peri-urban households rely on firewood to meet specific household energy needs, like space heating or heating water for bathing. Induction was rare and many induction owners reported zero use because the required equipment had never been installed by electricity companies, their stove had broken, or due to fears of high electricity costs. Our discussion is instructive for other countries because of Ecuador's long-standing clean fuel policies, robust LPG market and standardized cylinder recirculation model, and promotion of induction stoves.

Gastrointestinal defects in gallstone and cholecystectomized patients.

BACKGROUND AND AIM: Several gallstone patients complain of dyspeptic symptoms, irrespective of the presence of typical colicky pain. Symptoms often persist after a cholecystectomy. Systematic studies on dyspepsia and dynamic gastrointestinal motor function are missing in gallstone patients with preserved gallbladder or after a cholecystectomy. MATERIALS AND METHODS: Forty-six gallstone patients (age 55 ± 2 years; 15M, 31F) and 24 cholecystectomized patients (age 57 ± 2 years; 6M, 18F) (no difference in type and volume of gallstones between the two groups) were compared against a group of 65 healthy controls (age 51 ± 2 years; 30M, 35F). Dyspepsia occurring in the prior months was assessed by a questionnaire, gastric and gallbladder emptying by functional ultrasonography and orocecal transit time by a hydrogen breath test using a lactulose-enriched standard liquid meal. RESULTS: Gallstone patients had significantly greater dyspepsia, fasting and residual gallbladder volumes, and slower gallbladder emptying, gastric emptying and small intestinal transit time than controls. In cholecystectomized patients, gastric emptying further delayed, compared to gallstone patients and controls. CONCLUSION: Gallstone patients with the gallbladder "in situ" or after a cholecystectomy display dyspeptic symptoms. Symptoms are associated with multiple gastrointestinal motility defects involving the gallbladder, stomach and small intestine. After cholecystectomy, gastric emptying worsens.

Circulating CRP Levels Are Associated with Epicardial and Visceral Fat Depots in Women with Metabolic Syndrome Criteria.

Sexual dimorphism accounts for significant differences in adipose tissue mass and distribution. However, how the crosstalk between visceral and ectopic fat depots occurs and which are the determinants of ectopic fat expansion and dysfunction remains unknown. Here, we focused on the impact of gender in the crosstalk between visceral and epicardial fat depots and the role of adipocytokines and high-sensitivity C-reactive protein (hs-CRP). A total of 141 outward patients (both men and women) with one or more defining criteria for metabolic syndrome (MetS) were consecutively enrolled. For all patients, demographic and clinical data were collected and ultrasound assessment of visceral adipose tissue (VFth) and epicardial fat (EFth) thickness was performed. Hs-CRP and adipocytokine levels were assessed by enzyme-linked immunosorbent assay (ELISA). Men were characterized by increased VFth and EFth (p-value < 0.001 and 0.014, respectively), whereas women showed higher levels of adiponectin and leptin (p-value < 0.001 for both). However, only in women VFth and EFth significantly correlated between them (p = 0.013) and also with leptin (p < 0.001 for both) and hs-CRP (p = 0.005 and p = 0.028, respectively). Linear regression confirmed an independent association of both leptin and hs-CRP with VFth in women, also after adjustment for age and MetS (p = 0.012 and 0.007, respectively). In conclusion, men and women present differences in epicardial fat deposition and systemic inflammation. An intriguing association between visceral/epicardial fat depots and chronic low-grade inflammation also emerged. In women Although a further validation in larger studies is needed, these findings suggest a critical role of sex in stratification of obese/dysmetabolic patients.

Exercising the hepatobiliary-gut axis. The impact of physical activity performance.

BACKGROUND: Physical inactivity puts the populations at risk of several health problems, while regular physical activity brings beneficial effects on cardiovascular disease, mortality and other health outcomes, including obesity, glycaemic control and insulin resistance. The hepatobiliary tract is greatly involved in several metabolic aspects which include digestion and absorption of nutrients in concert with intestinal motility, bile acid secretion and flow across the enterohepatic circulation and intestinal microbiota. Several metabolic abnormalities, including nonalcoholic fatty liver as well as cholesterol cholelithiasis, represent two conditions explained by changes of the aforementioned pathways. MATERIALS AND METHODS: This review defines different training modalities and discusses the effects of physical activity in two metabolic disorders, that is nonalcoholic fatty liver disease (NAFLD) and cholelithiasis. Emphasis is given to pathogenic mechanisms involving intestinal bile acids, microbiota and inflammatory status. RESULTS: A full definition of physical activity includes the knowledge of aerobic and endurance exercise, metabolic equivalent tasks, duration, frequency and intensity, beneficial and harmful effects. Physical activity influences the hepatobiliary-gut axis at different levels and brings benefits to fat distribution, liver fat and gallbladder disease while interacting with bile acids as signalling molecules, intestinal microbiota and inflammatory changes in the body. CONCLUSIONS: Several beneficial effects of physical activity are anticipated on metabolic disorders linking liver steatosis, gallstone disease, gut motility, enterohepatic circulation of signalling bile acids in relation to intestinal microbiota and inflammatory changes.

Bile Acid Physiology.

The primary bile acids (BAs) are synthetized from colesterol in the liver, conjugated to glycine or taurine to increase their solubility, secreted into bile, concentrated in the gallbladder during fasting, and expelled in the intestine in response to dietary fat, as well as bio-transformed in the colon to the secondary BAs by the gut microbiota, reabsorbed in the ileum and colon back to the liver, and minimally lost in the feces. BAs in the intestine not only regulate the digestion and absorption of cholesterol, triglycerides, and fat-soluble vitamins, but also play a key role as signaling molecules in modulating epithelial cell proliferation, gene expression, and lipid and glucose metabolism by activating farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor-1 (GPBAR-1, also known as TGR5) in the liver, intestine, muscle and brown adipose tissue. Recent studies have revealed the metabolic pathways of FXR and GPBAR-1 involved in the biosynthesis and enterohepatic circulation of BAs and their functions as signaling molecules on lipid and glucose metabolism.

Bile Acids and Cancer: Direct and Environmental-Dependent Effects.

Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as singalling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i.e. prostate, breast) through a complex series of mechanisms including direct oxidative stress with DNA damage, apoptosis, epigenetic factors regulating gene expression, reduced/increased expression of nuclear receptors (mainly farnesoid X receptor, FXR) and altered composition of gut microbiota, also acting as a common interface between environmental factors (including diet, lifestyle, exposure to toxics) and the molecular events promoting cancerogenesis. Primary prevention strategies (i.e. changes in dietary habits and lifestyle, reduced exposure to environmental toxics) mainly able to modulate gut microbiota and the epigenome, and the therapeutic use of hydrophilic BAs to counterbalance the negative effects of the more hydrophobic BAs might be, in the near future, part of useful tools for cancer prevention and management.

The predictive capacity of the Glasgow-Blatchford score for the risk stratification of upper gastrointestinal bleeding in an emergency department.

OBJECTIVES: To assess the ability of the Glasgow Blatchford Score (GBS) system to identify the need for urgent upper gastrointestinal endoscopy (UGIE) in patients with upper gastrointestinal bleeding (UGIB). METHODS: An observational, retrospective study was carried out in all patients attended at the ER for suspected UGIB in one year. Patients were split into two categories -high-risk (>2) and low-risk ( < or = 2)- by means of the GBS system. RESULTS: A total of 60 patients were included. Of these, 46 were classified as "high-risk" (> 2) and 14 as "low-risk" ( < or = 2) subjects.The characteristics of patients in the low-risk group included: Mean age: 46.6 +/- 13.7 (18-88) years. Males/females: 7/7. Urgent endoscopy revealed: normal (50%; n = 7); esophagitis (21.4%; n = 3); gastritis (14.2%; n = 2); Mallory-Weiss syndrome (7.1%; n = 1); non-bleeding varices (7.1%; n = 1). The characteristics of patients in the high-risk group included: Mean age: 68.7 +/- 19.8 (31-91) years. Males/females: 30/16. Digestive endoscopy revealed: Gastric/duodenal ulcer (56.52%; n = 26); normal (17.39%; n = 8); esophagitis (8.69%; n = 4); gastritis (8.69%; n = 4); angioectasia (4.34%; n = 2); bleeding varices (4.34%; n = 2). Low-risk patients exhibited no lesions requiring urgent management during endoscopy, and the sensitivity of the GBS scale for high-risk UGIB detection was found to be 100% (95% CI: 86.27%, 99.71%), with a specificity of 48.28% (95% CI: 29.89, 67.1%). CONCLUSIONS: The GBS scale seems to accurately identify patients with low-risk UGIB, who may be managed on an outpatient basis and undergo delayed upper GI endoscopy at the outpatient clinic.

Using mid-upper arm circumference z -score measurement to support youth malnutrition screening as part of a global sports and wellness program and improve access to nutrition care.

Objective: Historically, mid-upper arm circumference (MUAC) has been instrumental to identifying malnutrition in children under 5 years living in resource restricted settings. Less attention is directed to at-risk, school-aged youth. Updated and validated pediatric age- and gender-specific MUAC growth curves expand malnutrition screening opportunities (2 months-18 years) including overweight/obesity. An innovative partnership was created to integrate MUAC z-score measurement trainings and screenings in the Real Madrid Foundation's (RMF) Social Sports Schools (S3) program, which provide sports and wellness programming to under-resourced communities. This work aimed to investigate the feasibility of leveraging non-healthcare professionals (non-HCPs) to identify malnutrition risk as part of RMF S3. Methods: This global, two-part program on malnutrition risk identification included training adult facilitators and screening children attending RMF S3. RMF facilitators were trained with didactic lectures on malnutrition, and practical hands-on learning of proper MUAC z-score tape measurement. Aggregate data on facilitators and the number of times to correctly administer the MUAC z-tape were recorded. Aggregate data on child malnutrition risk screenings were collected. Results: Nine countries participated representing Europe, Pacific Asia, Africa, Latin America, and North America. In total, 143 RMF facilitators were trained, and 318 children were screened across 11 sites. More than half of facilitators were male (56%, n = 80), and majority were coaches (41.3%, n = 59), followed by staff (25.2%, n = 36), and volunteers (16.1%, n = 23). Facilitator attempts ranged from 1 to 4 times for proper MUAC z-score administration with mean 2.12 (± 0.86). There were no significant differences for attempts among RMF facilitator types (p = 0.10). Sixteen percent (n = 51) of children screened were recommended for HCP referral, with concentrations in Pacific Asia (68%, n = 35), Latin America (24%, n = 12), and Africa (8%, n = 4). Conclusions: Findings from our sample demonstrate that integration of MUAC z-score based malnutrition risk screening within community sports and wellness programming among non-HCPs is feasible, and that some regions with less frequent access to routine health care may experience greater benefit from these programs. Equipping non-HCP facilitators in community sports and wellness programs with training on malnutrition screening provides a means to meet under-resourced families where they live to begin conversations around malnutrition risk with the hope of establishing additional pathways to care.

Impact of a home-based social welfare program on care for palliative patients in the Basque Country (SAIATU Program).

BACKGROUND: SAIATU is a program of specially trained in-home social assistance and companionship which, since February 2011, has provided support to end-of-life patients, enabling the delivery of better clinical care by healthcare professionals in Osakidetza (Basque Health Service), in Guipúzcoa (Autonomous Community of the Basque Country).In January 2012, a retrospective observational study was carried out, with the aim of describing the characteristics of the service and determining if the new social service and the associated socio-health co-ordination had produced any effect on the use of healthcare resources by end-of-life patients.The results of a comparison of a cohort of cases and controls demonstrated evidence that the program could reduce the use of hospital resources and promote the continuation of living at home, increasing the home-based activity of primary care professionals.The objective of this study is to analyse whether a program of social intervention in palliative care (SAIATU) results in a reduction in the consumption of healthcare resources and cost by end-of-life patients and promotes a shift towards a more community-based model of care. METHOD/DESIGN: Comparative prospective cohort study, with randomised selection of patients, which will systematically measure patient characteristics and their consumption of resources in the last 30 days of life, with and without the intervention of a social support team trained to provide in-home end-of-life care.For a sample of approximately 150 patients, data regarding the consumption of public healthcare resources, SAIATU activity, home hospitalisation teams, and palliative care will be recorded. Such data will also include information dealing with the socio-demographic and clinical characteristics of the patients and attending carers, as well as particular characteristics of patient outcomes (Karnofsky Index), and of the outcomes of palliative care received (Palliative Outcome Scale).Ethical approval for the study was given by the Clinical Research Ethics Committee of Euskadi (CREC-C) on 10 Dec 2012. DISCUSSION: The results of this prospective study will assist in verifying or disproving the hypothesis that the in-home social care offered by SAIATU improves the efficiency of healthcare resource usage by these patients (quality of life, symptom control).This project represents a dramatic advance with respect to other studies conducted to date, and demonstrates how, through the provision of personnel trained to provide social care for patients in the advanced stages of illness, and through strengthening the co-ordination of such social services with existing healthcare system resources, the resulting holistic structure obtains cost savings within the health system and improves the efficiency of the system as a whole.

Resilient clean cooking: Maintaining household clean cooking in Ecuador during the COVID-19 pandemic.

Decades of government subsidies for LPG and electricity have facilitated near-universal clean cooking access and use in Ecuador, placing the nation ahead of most other peer low- and middle-income countries. The widespread socio-economic impacts of the COVID-19 pandemic has threatened the resilience of clean cooking systems globally, including by altering households' ability to purchase clean fuels and policymakers' considerations about continuing subsidy programs. As such, assessing the resilience of clean cooking in Ecuador during the pandemic can offer important lessons for the international community, especially other countries looking to ensure resilient transitions to clean cooking. We study household energy use patterns using interviews, newspaper reports, government data on household electricity and LPG consumption, and household surveys [N = 200 across two rounds]. The LPG and electricity distribution systems experienced occasional disruptions to cylinder refill delivery and meter reading processes, respectively, which were associated with pandemic-related mobility restrictions. However, for the most part, supply and distribution activities by private and public companies continued without fundamental change. Survey participants reported increases in unemployment and reductions in household income as well as increased use of polluting biomass as a secondary fuel. Ecuador's LPG and electricity distribution systems were resilient throughout the pandemic, with only minimal interruption of the widespread provision of low-cost clean cooking fuels. Our findings inform the global audience concerned about the resilience of clean household energy use on the potential for clean fuel subsidies to facilitate continued clean cooking even during the COVID-19 pandemic.

"Compassionate City" in Patients with Advanced Illnesses and at the End of Life: A Pilot Study.

OBJECTIVES: To evaluate, in a Compassionate City pilot experience (Sevilla), the impact results on health in a population of people with advanced illness and at the end of life. METHODS: The project was undertaken in Sevilla, Spain, between January 2019 and June 2020. A longitudinal, descriptive study was conducted using a longitudinal cohort design with two cross-sectional measurements, pre and post intervention. All patients who entered the program on the start date were included. The networks of care around people with advanced illness and at the end of life, palliative care needs, quality of life, loneliness, anxiety, depression, caregivers' burden and family satisfaction were evaluated. The interventions were conducted by community promoters assigned to the "Sevilla Contigo, Compassionate City" program. RESULTS: A total of 83 people were included in the program. The average number of people involved in care at the beginning of the evaluations was 3.6, increasing to 6.1 at the end of the interventions. The average number of needs detected at the beginning was 15.58, and at the end of interventions, it was 16.56 out of 25. The unmet needs were those related to last wishes (40.7%), emotional relief (18.5%), entertainment (16%), help to walk up and down stairs (8.6%) and help to walk (6.2%). A total of 54.2% showed improved loneliness in the final evaluation. Out of 26 people evaluated for pre and post quality of life, 7 (26.9%) improved their quality of life in the general evaluation and 5 (19.2%) displayed improved anxiety/depression. A total of 6 people (28.6%) improved their quality-of-life thermometer scores. A total of 57.7% of caregivers improved their burden with a mean score of 17.8.

Equivalent Formulations of Optimal Control Problems with Maximum Cost and Applications.

We revisit the optimal control problem with maximum cost with the objective to provide different equivalent reformulations suitable to numerical methods. We propose two reformulations in terms of extended Mayer problems with state constraints, and another one in terms of a differential inclusion with upper-semi-continuous right member without state constraint. For the latter we also propose a scheme that approximates from below the optimal value. These approaches are illustrated and discussed in several examples.

Towards a Characterization of Background Music Audibility in Broadcasted TV.

In audiovisual contexts, different conventions determine the level at which background music is mixed into the final program, and sometimes, the mix renders the music to be practically or totally inaudible. From a perceptual point of view, the audibility of music is subject to auditory masking by other aural stimuli such as voice or additional sounds (e.g., applause, laughter, horns), and is also influenced by the visual content that accompanies the soundtrack, and by attentional and motivational factors. This situation is relevant to the music industry because, according to some copyright regulations, the non-audible background music must not generate any distribution rights, and the marginally audible background music must generate half of the standard value of audible music. In this study, we conduct two psychoacoustic experiments to identify several factors that influence background music perception, and their contribution to its variable audibility. Our experiments are based on auditory detection and chronometric tasks involving keyboard interactions with original TV content. From the collected data, we estimated a sound-to-music ratio range to define the audibility threshold limits of the barely audible class. In addition, results show that perception is affected by loudness level, listening condition, music sensitivity, and type of television content.

Exploring Liver Mitochondrial Function by 13C-Stable Isotope Breath Tests: Implications in Clinical Biochemistry.

The liver is at the crossroad of key metabolic processes, which include detoxification, glycolipidic storage and export, and protein synthesis. The gut-liver axis, moreover, provides hepatocytes with a series of bacterial products and metabolites, which contribute to maintain liver function in health and disease. Breath tests (BTs) are developed as diagnostic tools for indirect, rapid, noninvasive assessment of several metabolic processes in the liver. BTs monitor the appearance of CO2 in breath as a marker of a specific substrate metabolized in the liver, typically within microsomes, cytosol, or mitochondria. The noninvasiveness of BTs originates from the use of the, nonradioactive, naturally occurring stable isotope 13C marking a specific substrate which is metabolized in the liver, leading to the appearance of 13CO2 in expired air. Some substrates (ketoisocaproic acid, methionine, and octanoic acid) provide information about dynamic liver mitochondrial function in health and disease. In humans, the application of 13C-breath tests ranges from nonalcoholic and alcoholic liver diseases to liver cirrhosis, hepatocarcinoma, preoperative and postoperative assessment of liver function, and drug-induced liver damage. 13C-BTs are an indirect, cost-effective, and easy method to evaluate dynamic liver function and gastric kinetics in health and disease, with ongoing studies focusing on further applications in clinical medicine.

Protocols for Mitochondria as the Target of Pharmacological Therapy in the Context of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent metabolic chronic liver diseases in developed countries and puts the populations at risk of progression to liver necro-inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Mitochondrial dysfunction is involved in the onset of NAFLD and contributes to the progression from NAFLD to nonalcoholic steatohepatitis (NASH). Thus, liver mitochondria could become the target for treatments for improving liver function in NAFLD patients. This chapter describes the most important steps used for potential therapeutic interventions in NAFLD patients, discusses current options gathered from both experimental and clinical evidence, and presents some novel options for potentially improving mitochondrial function in NAFLD.

Adiponectin involved in portal flow hepatic extraction of 13C-methacetin in obesity and non-alcoholic fatty liver.

Obesity and non-alcoholic fatty liver disease (NAFLD) are high prevalence, inter-related conditions at increased risk for advanced liver diseases and related mortality. Adiponectin and leptin have divergent roles in the pathogenesis of fat accumulation and NAFLD. However, the relationships between body and liver fat accumulation, early modification of liver function and unbalanced adipokine levels are still scarcely explored. We studied by (13C)-methacetin breath test ((13C)-MBT) 67 adults stratified according to body mass index, and to presence/absence of ultrasonographic nonalcoholic fatty liver disease (uNAFLD). uNAFLD was detected in 20%, 73% and 96% of normal weight, overweight and obese subjects, respectively. The delta over baseline after 15 min (DOB15), a marker of hepatic extraction efficiency from portal blood flow, was lower in obese than in normal weight subjects, and in subjects with-, as compared to those without uNAFLD. The cumulative percent dose recovery after 30 min (cPDR30), a marker of liver microsomal function, was lower in uNAFLD patients. DOB15 was positively correlated with adiponectin levels in obese and in uNAFLD patients. uNAFLD patients also showed a positive correlation between cPDR30 values and adiponectin. Our data indicate the existence of early alterations of liver function in obese and in patients with uNAFLD. These dysfunctions are linked to altered leptin/adiponectin balance and can be identified noninvasively by (13C)-MBT.

(13C)-Methacetin breath test provides evidence of subclinical liver dysfunction linked to fat storage but not lifestyle.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is characterised by the presence of hepatic steatosis in the absence of other causes of secondary hepatic fat accumulation, and is usually associated with visceral, metabolically active obesity. However, the subclinical effects of body and liver fat accumulation on liver function are still unclear. METHODS: We used orally administered (13C)-methacetin and breath test to quantify the efficiency of hepatic extraction from portal blood flow and liver microsomal function in 81 participants, in relation to presence/absence of ultrasonographic NAFLD, extent of body fat accumulation, insulin resistance, dietary models, and lifestyle. RESULTS: NAFLD was present in 23% of participants with normal weight, and prevalence increased with body fat and insulin resistance. Fat accumulation, NAFLD, and insulin resistance were associated with decreased hepatic extraction efficiency, and liver microsomal function was impaired in moderate-to-severe NAFLD. Caloric intake, dietary models, and lifestyles had a minor role in promoting functional changes. CONCLUSIONS: The interplay between body fat accumulation, insulin resistance, and NAFLD is linked with altered hepatic extraction efficiency from blood flow and deranged microsomal function. Non-invasive diagnosis of subclinical alterations of liver function is relevant for primary and secondary prevention measures. Furthermore, the occurrence of NAFLD in lean individuals and the evidence that caloric intake, dietary models, and lifestyle played a minor role require further studies exploring the role of environmental factors in the natural history of these diseases. LAY SUMMARY: Obesity is progressively increasing worldwide and is paralleled by fat accumulation in the liver (non-alcoholic fatty liver disease [NAFLD]), the most common chronic liver disease worldwide. NAFLD can alter liver structure and function, with a variety of consequences ranging from asymptomatic and subclinical alterations to cirrhosis and cancer. (13C)-Methacetin breath test, a non-invasive diagnostic tool, can reveal early subclinical alterations of liver dynamic function in individuals with obesity and in patients with NAFLD.

Long-standing LPG subsidies, cooking fuel stacking, and personal exposure to air pollution in rural and peri-urban Ecuador.

Ecuador presents a unique case study for evaluating personal air pollution exposure in a middle-income country where a clean cooking fuel has been available at low cost for several decades. We measured personal PM2.5 exposure, stove use, and participant location during a 48-h monitoring period for 157 rural and peri-urban households in coastal and Andean Ecuador. While nearly all households owned a liquefied petroleum gas (LPG) stove and used it as their primary cooking fuel, one-quarter of households utilized firewood as a secondary fuel and 10% used induction stoves secondary to LPG. Stove use monitoring demonstrated clear within- and across-meal fuel stacking patterns. Firewood-owning participants had higher distributions of 48-h and 10-min PM2.5 exposure as compared with primary LPG and induction stove users, and this effect became more pronounced with firewood use during monitoring.Accounting for within-subject clustering, contemporaneous firewood stove use was associated with 101 µg/m3 higher 10-min PM2.5 exposure (95% CI: 94-108 µg/m3). LPG and induction cooking events were largely not associated with contemporaneous PM2.5 exposure. Our results suggest that firewood use is associated with average and short-term personal air pollution exposure above the WHO interim-I guideline, even when LPG is the primary cooking fuel.