The structure of the human 80S ribosome at 1.9 Å resolution reveals the molecular role of chemical modifications and ions in RNA.

The ribosomal RNA of the human protein synthesis machinery comprises numerous chemical modifications that are introduced during ribosome biogenesis. Here we present the 1.9 Å resolution cryo electron microscopy structure of the 80S human ribosome resolving numerous new ribosomal RNA modifications and functionally important ions such as Zn2+, K+ and Mg2+, including their associated individual water molecules. The 2'-O-methylation, pseudo-uridine and base modifications were confirmed by mass spectrometry, resulting in a complete investigation of the >230 sites, many of which could not be addressed previously. They choreograph key interactions within the RNA and at the interface with proteins, including at the ribosomal subunit interfaces of the fully assembled 80S ribosome. Uridine isomerization turns out to be a key mechanism for U-A base pair stabilization in RNA in general. The structural environment of chemical modifications and ions is primordial for the RNA architecture of the mature human ribosome, hence providing a structural framework to address their role in healthy states and in human diseases.

Novel approach to the derivation of dam breach parameters in 2D hydrodynamic modeling of earthquake induced dam failures.

Current methods of dam breach analyses adopt a deterministic approach. Applying these methods to Concrete Faced Rockfill Dams (CFRD) is fraught with huge levels of uncertainty, especially in the context of natural hazards. The frequency and magnitude of rainfall and earthquakes are higher in today's world. In the literature, the complete collapse of dams is modelled on dam breach parameters that define the dam break outflow but are not related to the return periods of natural hazards. As more new dams are constructed to control the floods in intra-plate seismic regions, this study presents a novel approach to the derivation of generalized dam break parameters for CFRD based on the structural analysis of Finite Element Model (FEM) simulations for peak ground accelerations corresponding to 475 and 2475 year return periods. Furthermore, the occurrence of rainfall and earthquake for different return periods are modelled using 2D hydrodynamic simulations. Results show the significance of generalized dam breach parameters for planning and managing CFRDs during earthquakes. The study emphasizes the utilization of structural analysis outputs for the hydraulic modeling of dam breaks, which will result in more specific and accurate dam break parameters. Additionally, the study has shown that the flood risk and the severity will increase with the intensity of earthquake and rainfall magnitudes. Disaster mitigation strategies can be optimized by considering the integrated occurrence of rainfall and earthquakes based on the probability of occurrence, demonstrated using a case-study dam. Another significant outcome of the study is the effect of soil saturation condition during a dam break, which reveals that areas within 40 km of the dam breach location might be worst affected.

Assessing the association between food environment and dietary inflammation by community type: a cross-sectional REGARDS study.

BACKGROUND: Communities in the United States (US) exist on a continuum of urbanicity, which may inform how individuals interact with their food environment, and thus modify the relationship between food access and dietary behaviors. OBJECTIVE: This cross-sectional study aims to examine the modifying effect of community type in the association between the relative availability of food outlets and dietary inflammation across the US. METHODS: Using baseline data from the REasons for Geographic and Racial Differences in Stroke study (2003-2007), we calculated participants' dietary inflammation score (DIS). Higher DIS indicates greater pro-inflammatory exposure. We defined our exposures as the relative availability of supermarkets and fast-food restaurants (percentage of food outlet type out of all food stores or restaurants, respectively) using street-network buffers around the population-weighted centroid of each participant's census tract. We used 1-, 2-, 6-, and 10-mile (~ 2-, 3-, 10-, and 16 km) buffer sizes for higher density urban, lower density urban, suburban/small town, and rural community types, respectively. Using generalized estimating equations, we estimated the association between relative food outlet availability and DIS, controlling for individual and neighborhood socio-demographics and total food outlets. The percentage of supermarkets and fast-food restaurants were modeled together. RESULTS: Participants (n = 20,322) were distributed across all community types: higher density urban (16.7%), lower density urban (39.8%), suburban/small town (19.3%), and rural (24.2%). Across all community types, mean DIS was - 0.004 (SD = 2.5; min = - 14.2, max = 9.9). DIS was associated with relative availability of fast-food restaurants, but not supermarkets. Association between fast-food restaurants and DIS varied by community type (P for interaction = 0.02). Increases in the relative availability of fast-food restaurants were associated with higher DIS in suburban/small towns and lower density urban areas (p-values < 0.01); no significant associations were present in higher density urban or rural areas. CONCLUSIONS: The relative availability of fast-food restaurants was associated with higher DIS among participants residing in suburban/small town and lower density urban community types, suggesting that these communities might benefit most from interventions and policies that either promote restaurant diversity or expand healthier food options.

Double-trouble: A rare case of co-infection with melioidosis and leptospirosis from Sri Lanka.

Melioidosis and leptospirosis are two emerging tropical infections that share somewhat similar clinical manifestations but require different methods of management. A 59-year-old farmer presented to a tertiary care hospital with an acute febrile illness associated with arthralgia, myalgia and jaundice, complicated by oliguric acute kidney injury and pulmonary haemorrhage. Treatment was initiated for complicated leptospirosis but with poor response. Blood culture was positive for Burkholderia pseudomallei and microscopic agglutination test (MAT) for leptospirosis was positive at the highest titres of 1:2560, confirming a co-infection of leptospirosis and melioidosis. The patient made a complete recovery with therapeutic plasma exchange (TPE), intermittent haemodialysis and intravenous (IV) antibiotics. Similar environmental conditions harbour melioidosis and leptospirosis, making co-infection a very real possibility. Co-infection should be suspected in patients from endemic areas with water and soil exposure. Using two antibiotics to cover both pathogens effectively is prudent. IV penicillin with IV ceftazidime is one such effective combination.

Assessing Measurement Invariance of a Land Use Environment Construct Across Levels of Urbanicity.

Variation in the land use environment (LUE) impacts the continuum of walkability to car dependency, which has been shown to have effects on health outcomes. Existing objective measures of the LUE do not consider whether the measurement of the construct varies across different types of communities along the rural/urban spectrum. To help meet the goals of the Diabetes Location, Environmental Attributes, and Disparities (LEAD) Network, we developed a national, census tract-level LUE measure which evaluates the road network and land development. We tested for measurement invariance by LEAD community type (higher density urban, lower density urban, suburban/small town, and rural) using multiple group confirmatory factor analysis. We determined that metric invariance does not exist; thus, measurement of the LUE does vary across community type with average block length, average block size, and percent developed land driving most shared variability in rural tracts and with intersection density, street connectivity, household density, and commercial establishment density driving most shared variability in higher density urban tracts. As a result, epidemiologic studies need to consider community type when assessing the LUE to minimize place-based confounding.

Glucocorticoid-induced adrenal insufficiency: an uncommon cause of hypercalcaemia.

Summary: Long-term use of exogenous glucocorticoids leads to the suppression of the hypothalamic-pituitary-adrenal axis. Therefore, if the glucocorticoid is withdrawn abruptly, patients will develop adrenal insufficiency. Hypercalcaemia is a rare but well-known complication of adrenal insufficiency. However, hypercalcaemia is a rare presentation of glucocorticoid-induced adrenal insufficiency (GI-AI). A 62-year-old patient with a past history of diabetes mellitus, ischaemic heart disease, stroke, hypertension and dyslipidaemia presented with polyuria, loss of appetite, malaise and vomiting for a duration of 2 months. His ionized calcium level was high at 1.47 mmol/L. Intact parathyroid hormone was suppressed (4.3 pg/mL) and vitamin D was in the insufficient range (24.6 ng/mL). Extensive evaluation for solid organ or haematological malignancy including contrast-enhanced CT chest, abdomen, pelvis, multiple myeloma workup and multiple tumour markers were negative. His synacthan-stimulated cortisol was undetectable thus confirming adrenal insufficiency. His adrenocorticotrophic hormone level was 3.82 pg/mL (4.7-48.8) excluding primary adrenal insufficiency. His MRI brain and other pituitary hormones were normal. Further inquiry revealed that the patient had taken over-the-counter dexamethasone on a regular basis for allergic rhinitis for more than 2 years and had stopped 2 weeks prior to the onset of symptoms. Therefore, a diagnosis of GI-AI leading to hypercalcemia was made. The patient was resuscitated with intravenous fluids and replacement doses of oral hydrocortisone were started with a plan of prolonged tailing off to allow the endogenous adrenal function to recover. His calcium normalized and he made a complete recovery. Learning points: Long-term use of glucocorticoids leads to the suppression of the hypothalamic-pituitary-adrenal axis. If the glucocorticoid is withdrawn abruptly, patients will develop adrenal insufficiency which is known as glucocorticoid-induced adrenal insufficiency. Adrenal insufficiency should be considered in the differential diagnosis of parathyroid hormone-independent hypercalcaemia. A thorough clinical history is of paramount importance in arriving at the correct diagnosis.

Eosinophil Progenitors in Patients With Non-Asthmatic Eosinophilic Bronchitis, Eosinophilic Asthma, and Normal Controls.

Objective: This study aims to explore the potential of in situ airway differentiation of eosinophil progenitors (EoPs) and hematopoietic progenitor cells (HPCs) in sputum and peripheral blood from patients with non-asthmatic eosinophilic bronchitis (NAEB), eosinophilic asthma (EA), and healthy controls (HC). Methods: Using flow cytometry, we enumerated sputum and blood HPCs and EoPs in patients with NAEB (n=15), EA (n=15), and HC (n=14) at baseline. Patients with NAEB and EA were then treated for 1 month with budesonide (200 µg, bid) or budesonide and formoterol (200/6 µg, bid), respectively. HPCs and EoPs in both compartments were re-evaluated. Results: At baseline, NAEB and EA both had significantly greater numbers of sputum but not blood HPCs and EoPs (p<0.05) compared to HC. There were no differences between NAEB and EA. After 1 month of inhaled corticosteroid (ICS) treatment, NAEB patients showed a significant improvement in cough symptoms, but the attenuation of sputum HPC and EoP levels was not significant. Conclusions: NAEB patients have increased airway levels of HPCs and EoPs. One-month treatment with ICS did not fully suppress the level of EoPs in NAEB. Controlling in situ airway differentiation of EoPs may control airway eosinophilia and provide long-term resolution of symptoms in NAEB.

Comparing Global and Spatial Composite Measures of Neighborhood Socioeconomic Status Across US Counties.

Area-level neighborhood socioeconomic status (NSES) is often measured without consideration of spatial autocorrelation and variation. In this paper, we compared a non-spatial NSES measure to a spatial NSES measure for counties in the USA using principal component analysis and geographically weighted principal component analysis (GWPCA), respectively. We assessed spatial variation in the loadings using a Monte Carlo randomization test. The results indicated that there was statistically significant variation (p = 0.004) in the loadings of the spatial index. The variability of the census variables explained by the spatial index ranged from 60 to 90%. We found that the first geographically weighted principal component explained the most variability in the census variables in counties in the Northeast and the West, and the least variability in counties in the Midwest. We also tested the two measures by assessing the associations with county-level diabetes prevalence using data from the CDC's US Diabetes Surveillance System. While associations of the two NSES measures with diabetes did not differ for this application, the descriptive results suggest that it might be important to consider a spatial index over a global index when constructing national county measures of NSES. The spatial approach may be useful in identifying what factors drive the socioeconomic status of a county and how they vary across counties. Furthermore, we offer suggestions on how a GWPCA-based NSES index may be replicated for smaller geographic scopes.

Bilateral Leydig Cell Hyperplasia: A Rare Cause of Postmenopausal Hirsutism.

BACKGROUND: Postmenopausal hirsutism could be due to a myriad of causes, including ovarian and adrenal tumours, ovarian hyperthecosis, exogenous androgens, and Cushing's syndrome. We report a patient who was found to have a rare cause of postmenopausal hirsutism. Case Presentation. A 64-year-old postmenopausal woman with a history of hypertension, thyrotoxicosis, and poorly controlled diabetes on multiple oral hypoglycaemic agents presented with gradual onset progressive excessive hair growth without any virilizing features. On examination, she did not have Cushingnoid features or clitoromegaly. Her hirsutism was quantified with Ferriman-Gallwey score which was 9. Her biochemical evaluation showed elevated testosterone levels with normal DHEAS, ODST, 17-OHP, and prolactin. Low-dose dexamethasone suppression test did not suppress testosterone more than 40%. Contrast-enhanced CT of the adrenal and pelvis did not show any adrenal or ovarian mass lesions. Transvaginal ultrasound scan showed bilateral prominent ovaries only. Combined adrenal and ovarian venous sampling was carried out to localize the source of excess androgen, but only the left adrenal vein was successfully cannulated which showed suppressed testosterone level compared to periphery. The patient underwent total abdominal hysterectomy and bilateral salphingo oophorectomy, and her testosterone level normalized postoperatively. Her glycaemic control improved. Histology showed evidence of bilateral diffuse ovarian Leydig cell hyperplasia. CONCLUSION: Evaluation of postmenopausal hirsutism needs careful history and examination followed by biochemical evaluation and imaging. While adrenal and ovarian venous sampling can help to arrive at a diagnosis, it is a technically demanding procedure with low success rates even at centers of excellence. Therefore, in such situations, bilateral oophorectomy may be the best course of action which will give the histological confirmation of the diagnosis. Successful treatment of hyperandrogenism can result in improvement of glycaemic control. Bilateral diffuse Leydig cell hyperplasia is a rare but important cause of postmenopausal hirsutism.

Evaluation of associations between estimates of particulate matter exposure and new onset type 2 diabetes in the REGARDS cohort.

BACKGROUND: Studies of PM2.5 and type 2 diabetes employ differing methods for exposure assignment, which could explain inconsistencies in this growing literature. We hypothesized associations between PM2.5 and new onset type 2 diabetes would differ by PM2.5 exposure data source, duration, and community type. METHODS: We identified participants of the US-based REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort who were free of diabetes at baseline (2003-2007); were geocoded at their residence; and had follow-up diabetes information. We assigned PM2.5 exposure estimates to participants for periods of 1 year prior to baseline using three data sources, and 2 years prior to baseline for two of these data sources. We evaluated adjusted odds of new onset diabetes per 5 µg/m3 increases in PM2.5 using generalized estimating equations with a binomial distribution and logit link, stratified by community type. RESULTS: Among 11,208 participants, 1,409 (12.6%) had diabetes at follow-up. We observed no associations between PM2.5 and diabetes in higher and lower density urban communities, but within suburban/small town and rural communities, increases of 5 µg/m3 PM2.5 for 2 years (Downscaler model) were associated with diabetes (OR [95% CI] = 1.65 [1.09, 2.51], 1.56 [1.03, 2.36], respectively). Associations were consistent in direction and magnitude for all three PM2.5 sources evaluated. SIGNIFICANCE: 1- and 2-year durations of PM2.5 exposure estimates were associated with higher odds of incident diabetes in suburban/small town and rural communities, regardless of exposure data source. Associations within urban communities might be obfuscated by place-based confounding.

Validation of the World Health Organization/ International Society of Hypertension (WHO/ISH) cardiovascular risk predictions in Sri Lankans based on findings from a prospective cohort study.

INTRODUCTION AND OBJECTIVES: There are no cardiovascular (CV) risk prediction models for Sri Lankans. Different risk prediction models not validated for Sri Lankans are being used to predict CV risk of Sri Lankans. We validated the WHO/ISH (SEAR-B) risk prediction charts prospectively in a population-based cohort of Sri Lankans. METHOD: We selected 40-64 year-old participants from the Ragama Medical Officer of Health (MOH) area in 2007 by stratified random sampling and followed them up for 10 years. Ten-year risk predictions of a fatal/non-fatal cardiovascular event (CVE) in 2007 were calculated using WHO/ISH (SEAR-B) charts with and without cholesterol. The CVEs that occurred from 2007-2017 were ascertained. Risk predictions in 2007 were validated against observed CVEs in 2017. RESULTS: Of 2517 participants, the mean age was 53.7 year (SD: 6.7) and 1132 (45%) were males. Using WHO/ISH chart with cholesterol, the percentages of subjects with a 10-year CV risk <10%, 10-19%, 20%-29%, 30-39%, ≥40% were 80.7%, 9.9%, 3.8%, 2.5% and 3.1%, respectively. 142 non-fatal and 73 fatal CVEs were observed during follow-up. Among the cohort, 9.4% were predicted of having a CV risk ≥20% and 8.6% CVEs were observed in the risk category. CVEs were within the predictions of WHO/ISH charts with and without cholesterol in both high (≥20%) and low(<20%) risk males, but only in low(<20%) risk females. The predictions of WHO/ISH charts, with-and without-cholesterol were in agreement in 81% of subjects (ĸ = 0.429; p<0.001). CONCLUSIONS: WHO/ISH (SEAR B) risk prediction charts with-and without-cholesterol may be used in Sri Lanka. Risk charts are more predictive in males than in females and for lower-risk categories. The predictions when stratifying into 2 categories, low risk (<20%) and high risk (≥20%), are more appropriate in clinical practice.

Methods for assessing cough sensitivity.

Cough sensitivity can be described as the reaction intensity of the cough reflex to different stimuli which activate chemically and mechanically sensitive vagal afferent nerves innervating airways and lungs. Measurement of cough reflex sensitivity plays an important role in revealing the underlying mechanisms of cough and evaluating the effects of pharmacological interventions. Besides, different responses to cough suppression therapies indicate the existence of cough hypersensitivity. In consideration of these factors stated above, cough sensitivity should therefore be assessed with a variety of cough challenge tests. Based on the neuroanatomical characteristics of the cough reflex, chemical challenge tests have been developed to objectively assess cough sensitivity. In cough inhalation challenges, capsaicin and citric acid are commonly used as the tussive agents to induce cough, which are validated for describing a profile of cough sensitivity to chemical irritants. Recently, mechanical methodologies have also been tried to measure the mechanical sensitivity of the cough reflex. Methodological consideration and selection are necessary for the reasonable assessment of cough sensitivity while employing cough challenges in clinical trials. Thus, in this review, we will focus on describing various methodologies of cough sensitivity measurement and, detailing some factors influencing on the accuracy of outcomes in the experimentally induced cough.

A patient with extensive cerebral calcification due to pseudohypoparathyroidism: a case report.

BACKGROUND: Pseudohypoparathyroidism(PHP) is a heterogeneous group of disorders due to impaired activation of c AMP dependant pathways following binding of parathyroid hormone (PTH) to its receptor. In PHP end organ resistance to PTH results in hypocalcaemia, hyperphosphataemia and high PTH levels. CASE PRESENTATION: A 59 year old male presented with a history of progressive impairment of speech and unsteadiness of gait for 1 week and acute onset altered behavior for 1 day and one episode of generalized seizure. His muscle power was grade four according to MRC (medical research council) scale in all limbs and Chovstek's and Trousseau's signs were positive. Urgent non contrast computed tomography scan of the brain revealed extensive bilateral cerebral and cerebellar calcifications. A markedly low ionized calcium level of 0.5 mmol/l, an elevated phosphate level of 9.5 mg/dl (reference range: 2.7-4.5 mg/dl) and an elevated intact PTH of 76.3 pg/l were noted. His renal functions were normal. His hypocalcemia was accentuated by the presence of hypomagnesaemia. His 25 hydroxy vitamin D level was only marginally low which could not account for severe hypocalcaemia. A diagnosis of pseudohypoparathyroidism without phenotypic defects, was made due to hypocalcaemia and increased parathyroid hormone levels with cerebral calcifications. The patient was treated initially with parenteral calcium which was later converted to oral calcium supplements. His coexisting Vitamin D deficiency was corrected with 1αcholecalciferol escalating doses. His hypomagnesaemia was corrected with magnesium sulphate parenteral infusions initially and later with oral preparations. With treatment there was a significant clinical and biochemical response. CONCLUSION: Pseudohypoparathyroidism can present for the first time in elderly resulting in extensive cerebral calcifications. Identification and early correction of the deficit will result in both symptomatic and biochemical response.

Assessment of the stretched penile length in Sri Lankan newborns

Introduction: Evaluation of the external genitalia is important in the routine neonatal examination, since abnormalities of the genitalia give clues to underlying endocrine disorders or structural malformations. Objectives: The objectives of the study were to document the stretched penile length (SPL) of healthy term neonates born following an uncomplicated delivery at a tertiary care hospital in Sri Lanka, and to establish the normative data for the SPL for Sri Lankan neonates. Method: This was a cross sectional observational study, carried out at post natal wards of the Castle Street Hospital for Women, Sri Lanka. The study was done on 369 stable newborns delivered at the gestational age of 37 to 42 weeks. A complete neonatal examination was performed by the principal investigator and the measurements of the weight, length, head circumference and stretched penile length were obtained. Mean penile length and statistically significant difference of penile length (SD) values were calculated. The correlation of mean penile length, period of gestation, birth weight and length were analysed. Result: The SPL positively correlated with the length of the baby. There is no statistically significant correlation of birth weight, head circumference and gestational age with the SPL. The mean SPL for term Sri Lankan new-borns was 3.03cm ± 0.37cm and the -2SD value was 2.29cm. Conclusions: Since the -2SD of SPL was 2.29cm, measurements less than this should be considered as micropenis.

Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry, Pharmacokinetics, and Molecular Targets.

Cancer causes considerable morbidity and mortality across the world. Socioeconomic, environmental, and lifestyle factors contribute to the increasing cancer prevalence, bespeaking a need for effective prevention and treatment strategies. Phytochemicals like plant polyphenols are generally considered to have anticancer, anti-inflammatory, antiviral, antimicrobial, and immunomodulatory effects, which explain their promotion for human health. The past several decades have contributed to a growing evidence base in the literature that demonstrate ability of polyphenols to modulate multiple targets of carcinogenesis linking models of cancer characteristics (i.e., hallmarks and nutraceutical-based targeting of cancer) via direct or indirect interaction or modulation of cellular and molecular targets. This evidence is particularly relevant for the lignans, an ubiquitous, important class of dietary polyphenols present in high levels in food sources such as flaxseed. Literature evidence on lignans suggests potential benefit in cancer prevention and treatment. This review summarizes the relevant chemical and pharmacokinetic properties of dietary polyphenols and specifically focuses on the biological targets of flaxseed lignans. The consolidation of the considerable body of data on the diverse targets of the lignans will aid continued research into their potential for use in combination with other cancer chemotherapies, utilizing flaxseed lignan-enriched natural products.

Randomized, double-blind study on intralesional metronidazole versus intralesional sodium stibogluconate in Leishmania donovani cutaneous leishmaniasis.

OBJECTIVES: The aim of our study was to assess the efficacy of intralesional metronidazole on Leishmania donovani cutaneous leishmaniasis (CL). MATERIAL AND METHODS: A total of 188 patients with CL were randomly allocated to intralesional sodium stibogluconate (SSG) and intralesional metronidazole. Cure was assessed after 1-10 injections. Cure rates were assessed for statistical significance using chi-square test at p = .05 level (SLCTR/2014/028). RESULTS: When the treatment cutoff was taken at 100%, the rate of cure for SSG (n = 64, 65.6%) was higher than that of metronidazole (n = 45, 48.9%): statistically significant at p < .05 level (Yates corrected chi-square 5.37, df = 1, p < .5). When the treatment cutoff was taken at >80%, the rate of cure for SSG (n = 75, 77.1%) was also higher than that of metronidazole (n = 58, 63.0%): statistically significant at p < .05 level (Yates corrected chi-square 4.46, df = 1, p < .5). Since it is based on a smaller sample, we estimated the statistical power of the test at a cutoff of 100% [above 80%] results identified a risk ratio of 1.4 [1.3], and a statistical power based on normal approximation at 74.8% [70.0%], respectively. CONCLUSION: This study showed that intralesional SSG has the best response against CL, while intralesional metronidazole was an effective alternative treatment.

Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka.

INTRODUCTION: While patients with non-alcoholic fatty liver disease (NAFLD) are mostly overweight or obese, some are lean. METHODS: In a community-based follow-up study (baseline and follow-up surveys performed in 2007 and 2014), we investigated and compared the clinical characteristics, body composition, metabolic associations and outcomes, and other risk factors among individuals with lean (BMI < 23 kg/m2) NAFLD, non-lean (BMI ≥ 23 kg/m2) NAFLD and those without NAFLD. To investigate associations of selected genetic variants, we performed a case-control study between lean NAFLD cases and lean non-NAFLD controls. RESULTS: Of the 2985 participants in 2007, 120 (4.0%) had lean NAFLD and 816 (27.3%) had non-lean NAFLD. 1206 (40.4%) had no evidence of NAFLD (non-NAFLD). Compared to non-lean NAFLD, lean NAFLD was commoner among males (p < 0.001), and had a lower prevalence of hypertension (p < 0.001) and central obesity (WC < 90 cm for males, < 80 cm for females) (p < 0.001) without prominent differences in the prevalence of other metabolic comorbidities at baseline survey. Of 2142 individuals deemed as either NAFLD or non-NAFLD in 2007, 704 NAFLD individuals [84 lean NAFLD, 620 non-lean NAFLD] and 834 individuals with non-NAFLD in 2007 presented for follow-up in 2014. There was no difference in the occurrence of incident metabolic comorbidities between lean NAFLD and non-lean NAFLD. Of 294 individuals who were non-NAFLD in 2007 and lean in both 2007 and 2014, 84 (28.6%) had developed lean NAFLD, giving an annual incidence of 4.1%. Logistic regression identified the presence of diabetes at baseline, increase in weight from baseline to follow-up and a higher educational level as independent risk factors for the development of incident lean NAFLD. NAFLD association of PNPLA3 rs738409 was more pronounced among lean individuals (one-tailed p < 0.05) compared to the whole cohort sample. CONCLUSION: Although lean NAFLD constitutes a small proportion of NAFLD, the risk of developing incident metabolic comorbidities is similar to that of non-lean NAFLD. A PNPLA3 variant showed association with lean NAFLD in the studied population. Therefore, lean NAFLD also warrants careful evaluation and follow-up.