Innate immune cells in liver inflammation

Innate immune system is the first line of defence against invading pathogens that is critical for the overall survival of the host. Human liver is characterised by a dual blood supply, with 80% of blood entering through the portal vein carrying nutrients and bacterial endotoxin from the gastrointestinal tract. The liver is thus constantly exposed to antigenic loads. Therefore, pathogenic microorganism must be efficiently eliminated whilst harmless antigens derived from the gastrointestinal tract need to be tolerized in the liver. In order to achieve this, the liver innate immune system is equipped with multiple cellular components; monocytes, macrophages, granulocytes, natural killer cells, and dendritic cells which coordinate to exert tolerogenic environment at the same time detect, respond, and eliminate invading pathogens, infected or transformed self to mount immunity. This paper will discuss the innate immune cells that take part in human liver inflammation, and their roles in both resolution of inflammation and tissue repair

Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study

Background & aimsThere are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD) in people with type 2 diabetes mellitus (T2DM) compared with people without T2DM. We assessed the time to fibrosis progression in people with T2DM compared with people without T2DM in a large, multicenter, study of people with NAFLD who had paired liver biopsies.MethodsThis study included 447 adult participants (64% were female) with NAFLD who had paired liver biopsies more than 1 year apart. Liver histology was systematically assessed by a central pathology committee blinded to clinical data. The primary outcome was the cumulative incidence of a ≥1-stage increase in fibrosis in participants with T2DM compared with participants without T2DM.ResultsThe mean (SD) age and body mass index (calculated as weight in kilograms divided by the square of the height in meters) were 50.9 (11.5) years and 34.7 (6.3), respectively. The median time between biopsies was 3.3 years (interquartile range, 1.8-6.1 years). Participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at 4 years (24% vs 20%), 8 years (60% vs 50%), and 12 years (93% vs 76%) (P = .005). Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio, 1.69; 95% CI, 1.17-2.43; P = .005). The cumulative incidence of fibrosis regression by ≥1 stage was similar in participants with T2DM compared with participants without T2DM (P = .24).ConclusionsIn this large, multicenter cohort study of well-characterized participants with NAFLD and paired liver biopsies, we found that fibrosis progressed faster in participants with T2DM compared with participants without T2DM. These data have important implications for clinical practice and trial design

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Biodiversity recovery of Neotropical secondary forests

Old-growth tropical forests harbor an immense diversity of tree species but are rapidly being cleared, while secondary forests that regrow on abandoned agricultural lands increase in extent. We assess how tree species richness and composition recover during secondary succession across gradients in environmental conditions and anthropogenic disturbance in an unprecedented multisite analysis for the Neotropics. Secondary forests recover remarkably fast in species richness but slowly in species composition. Secondary forests take a median time of five decades to recover the species richness of old-growth forest (80% recovery after 20 years) based on rarefaction analysis. Full recovery of species composition takes centuries (only 34% recovery after 20 years). A dual strategy that maintains both old-growth forests and species-rich secondary forests is therefore crucial for biodiversity conservation in human-modified tropical landscapes. Copyright © 2019 The Authors, some rights reserved

Bilateral Anterior Thigh Thickness: A New Diagnostic Tool for the Identification of Low Muscle Mass?

OBJECTIVES To develop an ultrasonographic scanning protocol that included an assessment of muscle size [the proposed Bilateral Anterior Thigh Thickness (BATT)] and quality (echogenicity) to support the diagnosis of sarcopenia in a clinical setting. To determine the relationship of BATT and ultrasound echogenicity with physical function parameters of sarcopenia and test the reliability of ultrasound echogenicity measurements. DESIGN Observational study. SETTING AND PARTICIPANTS The BATT criteria were determined from a reference population of 113 healthy younger adults and tested in 39 healthy older adults and 31 frail older adults. METHODS Ultrasonography was used to measure the thickness of rectus femoris and vastus intermedius bilaterally; the thickness measurements were summed to calculate the BATT. Diagnostic criteria for low muscle size were calculated from the reference population. Echogenicity was assessed using freeze-frame images. All individuals underwent anthropological, frailty, and physical performance assessments. RESULTS The mean (standard deviation) BATTs for the subsamples were as follows: healthy young women (n = 54), 60.6 mm (±11.1); healthy young men (n = 59), 75.8 mm (±10.71); healthy older women (n = 27), 38.4 mm (±7.18); healthy older men (n = 13), 47.5 mm (±10.8); frail older women (n = 17), 29.2 mm (±11.4); and frail older men (n = 14), 27.3 mm (±13.9). The calculated cutoffs for low muscle size in older adults using the BATT criteria were 38.5 mm in women and 54.4 mm in men in this population. The BATT was correlated with grip strength (ρ = 0.750, P < .001 for women; ρ = 0.619, P < .001 for men) and walk speed (ρ = -0.599, P < .001 for women; ρ = -0.324, P = .003 for men). Ultrasound echogenicity increased with age and frailty. Lay sonographers were able to reliably reproduce the same muscle thickness measurements but not the same muscle echogenicity measurements. CONCLUSIONS/IMPLICATIONS The data support the use of ultrasonography to identify low muscle size in sarcopenia. Ultrasonography provides a pragmatic diagnostic tool that is noninvasive, without radiation exposure, and usable in both community and hospital settings. The proposed BATT criteria could be used to identify low muscle size in clinical practice and research, and in this study have excellent correlation with physical parameters of muscle health. However, this now needs testing in a validation cohort. Ultrasound echogenicity has been demonstrated to be an important surrogate marker of muscle health, but difficulties with reproducibility preclude its widespread clinical use

Gender Disparity in Expression of Sarcopenia in Haemodialysis Recipients: Analysis from the FITNESS Cohort

Background. There has been little exploration of the interplay between sarcopenia and frailty in haemodialysis, particularly regarding gender difference. We aimed to (1) assess whether ultrasound-derived low muscle mass (LMM) and sarcopenia are more common in male or female haemodialysis recipients; (2) assess whether age influences any observed gender difference, and (3) explore the interplay between sarcopenia, frailty, and gender in haemodialysis recipients. Methods. This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis with frailty phenotype (FP) scores. Bilateral anterior thigh thickness (BATT) was obtained according to an established ultrasound protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, LMM, and sarcopenia with a priori covariables, stratified by gender. Results. In total of 223 studies, participants had ultrasound measurements. Males showed greater prevalence of LMM. On adjusted analyses, LMM was associated with lower hand grip strength in males (β = −4.17; 95% C.I. −7.57 to −0.77; P=0.02), but not females (β = −1.88; 95% C.I. −5.41 to 1.64; P=0.29). LMM was also associated with slower walking speed in both males (β = −0.115; 95% C.I. −0.258 to −0.013; P=0.03) and females (β = −0.152; 95% C.I. −0.300 to −0.005; P=0.04). Sarcopenia was associated with greater odds of frailty on adjusted models in males (OR = 9.86; 95% C.I. 1.8 to 54.0; P=0.01), but not females (OR = 5.16; 95% C.I. 0.22 to 124; P=0.31). Conclusions. The clinical expression and significance of sarcopenia differ substantially between males and females on haemodialysis. Further work is required to elucidate underlying mechanisms and guide tailored treatment

Ultrasound quadriceps muscle thickness is variably associated with frailty in haemodialysis recipients

Abstract Background Ultrasonographic quantitation of quadriceps muscle mass is increasingly used for assessment of sarcopenia, but its relationship with frailty in haemodialysis recipients is not known. This study explores the relationship between ultrasound-derived bilateral anterior thigh thickness (BATT), sarcopenia, and frailty by common frailty tools (Frailty Phenotype [FP], Frailty Index [FI], Edmonton Frailty [EFS], and Clinical Frailty Scale [CFS]). Methods This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis recipients deeply phenotyped for frailty. Ultrasound assessment of BATT was obtained with participants at an angle of ≤45°, with legs outstretched and knees resting at 10°-20°, according to an established protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, Low Muscle Mass (LMM), and sarcopenia with stepwise adjustment for a priori covariables. Results In total 223 study participants had ultrasound measurements. Frailty ranged from 34% for FP to 58% for FI. BATT was associated with increasing frailty on simple linear regression by all frailty tools, but lost significance on addition of covariables. Upon dichotomising frailty tools into Frail/Not Frail, BATT was associated with frailty by all tools on univariable analyses, but only retained association for EFS on the fully adjusted model (OR 0.97, 95% C.I. 0.94–1.00, P = 0.05). Conclusions Ultrasound measures of quadriceps thickness is variably associated with frailty in prevalent haemodialysis recipients, dependent upon the frailty tool used, but not independent of other variables. Further work is required to establish the added value of sarcopenia measurement in frail haemodialysis patients. Trial registration Clinicaltrials.gov : NCT03071107 registered 06/03/2017