Resistin expression correlates with steatohepatitis in morbidly obese patients

Background

Morbidly obese patients are at risk for nonalcoholic steatohepatitis (NASH) even in the absence of risk factors for liver disease. Unfortunately, NASH is usually not clinically evident, and a definitive, noninvasive test for NASH does not exist. Resistin, a cytokine originating from adipose tissue, is involved in insulin resistance and also initiates proinflammatory signaling from hepatic stellate cells. This study explores the relationship between resistin expression and liver pathology in bariatric surgery patients.

Methods

Blood samples from 30 patients undergoing bariatric surgery were collected. Total RNA was extracted and cDNA was synthesized. Quantitative RT-PCR was used to quantify relative gene expression using 18s rRNA gene as an internal control. Wedge liver biopsies from these patients were sectioned and stained. Based on a previously published scoring method, biopsies were assigned an overall NASH severity score and subscores for steatosis, inflammation, and fibrosis. Results were analyzed by using Student’s t test.

Results

Resistin mRNA levels ranged from 0.5 to 9.7. A group of five patients with very high resistin expression (>4) was identified. These patients had a significantly higher average NASH score compared with the rest of the group (7.9 vs. 4.48, p = 0.019). Steatosis and inflammation scores were significantly higher in the high-resistin group (p < 0.05 for both comparisons). There also was a trend toward higher fibrosis score in this group, which approached statistical significance (p = 0.051).

Conclusions

In morbidly obese patients, high resistin expression in serum is associated with hepatic steatosis, inflammation, and fibrosis. The development of elevated resistin expression may represent a link between obesity and the onset of steatohepatitis.     

Behavioral and neural responses to gustatory stimuli delivered non-contingently through intra-oral cannulas

The act of eating requires a decision by an animal to place food in its mouth. The reasons to eat are varied and include hunger as well as the food's expected reward value. Previous studies of tastant processing in the rat primary gustatory cortex (GC) have used either anesthetized or awake behaving preparations that yield somewhat different results. Here we have developed a new preparation in which we explore the influences of intra-oral and non-contingent tastant delivery on rats' behavior and on their GC neural responses. We recorded single-unit activity in the rat GC during two sequences of tastant deliveries, PRE and POST, which were separated by a waiting period. Six tastants ranging in hedonic value from sucrose to quinine were delivered in the first two protocols called 4TW and L-S. In the third one, the App L-S protocol, only hedonically positive tastants were used. In the 4TW protocol, tastants were delivered in blocks whereas in the two L-S protocols tastants were randomly interleaved. In the 4TW and L-S protocols the probability of ingesting tastants in the PRE sequence decreased exponentially with the trial number. Moreover, in both protocols this decrease was greater in the POST than in the PRE sequence likely because the subjects learned that unpleasant tastants were to be delivered. In the App L-S protocol the decrease in ingestion was markedly slower than in the other protocols, thus supporting the hypothesis that the decrease in appetitive behavior arises from the non-contingent intra-oral delivery of hedonically negative tastants like quinine. Although neuronal responses in the three protocols displayed similar variability levels, significant differences existed between the protocols in the way the variability was partitioned between chemosensory and non-chemosensory neurons. While in the 4TW and L-S protocols the former population displayed more changes than the latter, in the App L-S protocol variability was homogeneously distributed between the two populations. We posit that these tuning changes arise, at least in part, from compounds released upon ingestion, and also from differences in areas of the oral cavity that are bathed as the animals ingest or reject the tastants.     

Reliability of cardiovascular reactivity to stress: internal consistency

Research on the reliability of cardiovascular reactivity has focused on temporal stability and intertask consistency with only modest results. The present study evaluated the internal consistency reliability of cardiovascular reactivity in three large samples of adolescents and young adults (N=326, 136, and 142). Impedance cardiographic and blood pressure measures were recorded at rest and during standard laboratory stress tasks (math, video game, cold pressor). The reliability of cardiovascular reactivity within tasks, as assessed by Cronbach's alpha coefficient of internal consistency, ranged from alpha=.83 to .96 for 4-min to 5-min math tasks, and alpha=.65 to .94 for 3-min video game and cold pressor tasks. Although highly reliable within tasks, cardiovascular reactivity was less reliable across tasks, even within a single testing session. Possible reasons for the discrepancy between internal consistency and intertask consistency are discussed.     

Closure of a nonhealing gastrocutaneous fistula using an endoscopic clip

Gastrocutaneous fistula after gastrostomy tube removal may persist for a prolonged period. We present a case of a 58-year-old woman with a GCF that had persisted for 5 months following the removal of an endoscopically-placed gastrostomy tube (PEG). Conservative therapy with anti-acid medications and administering motility agents was unsuccessful. For the closure of the GCF, the endoscopic metal clips were used to close the fistula.     

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (N_females = 130; N_males = 81) and 567 age-matched controls (N_females = 317; N_males = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co-morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT-genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192–201, 2020