Alcohol consumption and the risk of liver disease: a nationwide, population-based study

IntroductionAlthough most patients with alcohol-related liver disease (ALD) have a history of prolonged and heavy drinking, there is no clear threshold defining the level of alcohol consumption that leads to ALD. We aimed to evaluate the correlation between average alcohol consumption and the risk of liver disease and to determine the threshold for clinically significant alcohol consumption.Materials and methodsUsing the Korean National Health Insurance database, we identified participants who underwent a health-screening program in 2010 and 2011 and retrospectively analyzed their data until 2019. To diagnose and categorize the extracted participants, we used the International Classification of Diseases version 10 and Fatty Liver Index. The primary outcome was to determine the incidence of newly diagnosed liver-related diseases during the observation period and compare the incidence of liver-related diseases among non-drinkers and drinkers based on the amount of alcohol consumption.ResultsA total of 53,006 patients were enrolled and followed-up for a median of 8.4 years, during which 1,509 cases of liver-related diseases occurred. The participants were divided into five groups: no alcohol consumption (n = 31,359), 1st quartile (n = 5,242), 2nd quartile (n = 5,704), 3rd quartile (n = 5,337), and 4th quartile (n = 5,364). The corresponding number of glasses of alcohol consumed per week for each quantile (Q1, Q2, Q3, and Q4) was labeled 2.5 ± 1.1 standard units (1 standard unit = 8 g alcohol), 5.4 ± 1.9 standard units, 11.5 ± 3.3 standard units, and 27.9 ± 18.2 standard units, respectively. Compared with non-drinkers, the risk of liver-related disease was found to be higher in Q1 drinkers (adjusted hazard ratio [aHR], 1.09; 95% CI, 0.90–1.33), Q2 drinkers (aHR, 1. 10; 95% CI, 0.91–1.32), Q3 drinkers (aHR, 1.33; 95% CI, 1.11–1.59), and Q4 drinkers (aHR, 1.47; 95% CI, 1.24–1.75).ConclusionWe report that our study has shown that drinking more than 11.5 ± 3.3 standard units/week (92 ± 26.4 g/week) significantly increases the risk of developing liver-related diseases. Therefore, as a preventive measure to reduce the risk of developing liver disease, alcohol consumption should be limited beyond traditionally recommended levels

Common Variants in the Glycerol Kinase Gene Reduce Tuberculosis Drug Efficacy

Despite the administration of multiple drugs that are highly effective in vitro, tuberculosis (TB) treatment requires prolonged drug administration and is confounded by the emergence of drug-resistant strains. To understand the mechanisms that limit antibiotic efficacy, we performed a comprehensive genetic study to identify Mycobacterium tuberculosis genes that alter the rate of bacterial clearance in drug-treated mice. Several functionally distinct bacterial genes were found to alter bacterial clearance, and prominent among these was the glpK gene that encodes the glycerol-3-kinase enzyme that is necessary for glycerol catabolism. Growth on glycerol generally increased the sensitivity of M. tuberculosis to antibiotics in vitro, and glpK-deficient bacteria persisted during antibiotic treatment in vivo, particularly during exposure to pyrazinamide-containing regimens. Frameshift mutations in a hypervariable homopolymeric region of the glpK gene were found to be a specific marker of multidrug resistance in clinical M. tuberculosis isolates, and these loss-of-function alleles were also enriched in extensively drug-resistant clones. These data indicate that frequently observed variation in the glpK coding sequence produces a drug-tolerant phenotype that can reduce antibiotic efficacy and may contribute to the evolution of resistance. IMPORTANCE: TB control is limited in part by the length of antibiotic treatment needed to prevent recurrent disease. To probe mechanisms underlying survival under antibiotic pressure, we performed a genetic screen for M. tuberculosis mutants with altered susceptibility to treatment using the mouse model of TB. We identified multiple genes involved in a range of functions which alter sensitivity to antibiotics. In particular, we found glycerol catabolism mutants were less susceptible to treatment and that common variation in a homopolymeric region in the glpK gene was associated with drug resistance in clinical isolates. These studies indicate that reversible high-frequency variation in carbon metabolic pathways can produce phenotypically drug-tolerant clones and have a role in the development of resistance

A Novel In Vitro Sensing Configuration for Retinal Physiology Analysis of a Sub-Retinal Prosthesis

This paper presents a novel sensing configuration for retinal physiology analysis, using two microelectrode arrays (MEAs). In order to investigate an optimized stimulation protocol for a sub-retinal prosthesis, retinal photoreceptor cells are stimulated, and the response of retinal ganglion cells is recorded in an in vitro environment. For photoreceptor cell stimulation, a polyimide-substrate MEA is developed, using the microelectromechanical systems (MEMS) technology. For ganglion cell response recording, a conventional glass-substrate MEA is utilized. This new sensing configuration is used to record the response of retinal ganglion cells with respect to three different stimulation methods (monopolar, bipolar, and dual-monopolar stimulation methods). Results show that the geometrical relation between the stimulation microelectrode locations and the response locations seems very low. The threshold charges of the bipolar stimulation and the monopolar stimulation are in the range of 10∼20 nC. The threshold charge of the dual-monopolar stimulation is not obvious. These results provide useful guidelines for developing a sub-retinal prosthesis

Induction of Remission is Difficult due to Frequent Relapse during Tapering Steroids in Korean Patients with Polymyalgia Rheumatica

Polymyalgia rheumatica is an inflammatory disease affecting elderly and involving the shoulder and pelvic girdles. No epidemiological study of polymyalgia rheumatica was conducted in Korea. We retrospectively evaluated patients with polymyalgia rheumatica followed up at the rheumatology clinics of 10 tertiary hospitals. In total 51 patients, 36 patients (70.6%) were female. Age at disease onset was 67.4 yr. Twenty-three patients (45.1%) developed polymyalgia rheumatica in winter. Shoulder girdle ache was observed in 45 patients (90%) and elevated erythrocyte sedimentation rate (> 40 mm/h) in 49 patients (96.1%). Initial steroid dose was 23.3 mg/d prednisolone equivalent. Time to normal erythrocyte sedimentation rate was 4.1 months. Only 8 patients (15.7%) achieved remission. Among 41 patients followed up, 28 patients (68.3%) had flare at least once. Number of flares was 1.5 ± 1.6. The frequency of flare was significantly lower in patients with remission (P = 0.02). In Korea, polymyalgia rheumatica commonly develops during winter. Initial response to steroid is fairly good, but the prognosis is not benign because remission is rare with frequent relapse requiring long-term steroid treatment

Normative Values and Correlates of Mean Common Carotid Intima-Media Thickness in the Korean Rural Middle-aged Population: The Atherosclerosis RIsk of Rural Areas iN Korea General Population (ARIRANG) Study

Carotid intima-media thickness (CIMT) is considered as a surrogate marker for cardiovascular disease (CVD). We determined the normative value of CIMT and correlates of CVD risk factors and Framingham risk score (FRS) in Korean rural middle-aged population. We measured CIMT with a B-mode ultrasonography in 1,759 subjects, aged 40 to 70 yr, in a population-based cohort in Korea. A healthy reference sample (n = 433) without CVD, normal weight and normal metabolic parameters was selected to establish normative CIMT values. Correlates between CIMT and conventional CVD risk factors were assessed in the entire population. Mean values of CIMT (in mm) for healthy reference sample aged 40-49, 50-59, and 60-70 yr were 0.55, 0.59, and 0.66 for men and 0.48, 0.55, and 0.63 for women, respectively. In multivariate regression analysis, CIMT was correlated with older age, higher BMI, male gender, higher LDL-cholesterol level and history of diabetes mellitus. The mean CIMT was also correlated with FRS in both gender (r2 = 0.043, P < 0.01 for men; r2 = 0.142, P < 0.01 for women). We identified normative value of CIMT for the healthy Korean rural middle-aged population. The CIMT is associated with age, obesity, gender, LDL-cholesterol, diabetes mellitus and FRS

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes