Prognostic Utility of Left Atrial Strain From MRI Feature Tracking in Ischemic and Nonischemic Dilated Cardiomyopathy: A Multicenter Study.

BACKGROUND. MRI-based prognostic evaluation in patients with dilated cardiomyopathy (DCM) has historically used markers of late gadolinium enhancement (LGE) and feature tracking (FT)-derived left ventricular global longitudinal strain (LVGLS). Early data indicate that FT-derived left atrial strain (LAS) parameters, including reservoir, conduit, and booster, may also have prognostic roles in such patients. OBJECTIVE. The purpose of our study was to evaluate the prognostic utility of LAS parameters, derived from MRI FT, in patients with ischemic or nonischemic DCM, including in comparison with the traditional parameters of LGE and LVGLS. METHODS. This retrospective study included 811 patients with ischemic or nonischemic DCM (median age, 60 years; 640 men, 171 women) who underwent cardiac MRI at any of five centers. FT-derived LAS parameters and LVGLS were measured using two- and four-chamber cine images. LGE percentage was quantified. Patients were assessed for a composite outcome of all-cause mortality or heart failure hospitalization. Multivariable Cox regression analyses including demographic characteristics, cardiovascular risk factors, medications used, and a wide range of cardiac MRI parameters were performed. Kaplan-Meier analyses with log-rank tests were also performed. RESULTS. A total of 419 patients experienced the composite outcome. Patients who did, versus those who did not, experience the composite outcome had larger LVGLS (-6.7% vs -8.3%, respectively; p < .001) as well as a smaller LAS reservoir (13.3% vs 19.3%, p < .001), LAS conduit (4.7% vs 8.0%, p < .001), and LAS booster (8.1% vs 10.3%, p < .001) but no significant difference in LGE (10.1% vs 11.3%, p = .51). In multivariable Cox regression analyses, significant independent predictors of the composite outcome included LAS reservoir (HR = 0.96, p < .001) and LAS conduit (HR = 0.91, p < .001). LAS booster and LGE were not significant independent predictors in the models. LVGLS was a significant independent predictor only in a model that initially included LAS booster but not the other LAS parameters. In Kaplan-Meier analysis, all three LAS parameters were significantly associated with the composite outcome (p < .001). CONCLUSION. In this multicenter study, LAS reservoir and LAS conduit were significant independent prognostic markers in patients with ischemic or nonischemic DCM, showing greater prognostic utility than the currently applied markers of LVGLS and LGE. CLINICAL IMPACT. FT-derived LAS analysis provides incremental prognostic information in patients with DCM.

Adinazolam, a Benzodiazepine-Type New Psychoactive Substance, Has Abuse Potential and Induces Withdrawal Symptoms in Rodents.

Adinazolam (ADZ) is a benzodiazepine-type new psychoactive substance (NPS) with anxiolytic, anticonvulsant, and antidepressant effects. High ADZ doses have been reported to impair psychomotor performance and memory; however, the abuse potential and drug dependence of ADZ have not yet been fully investigated. In this study, we evaluated whether ADZ has abuse potential and leads to drug dependence and withdrawal symptoms. The intravenous self-administration (IVSA) test revealed that ADZ (0.01, 0.03, and 0.1 mg/kg/infusion) was self-administered significantly above vehicle levels, suggesting the reinforcing effect of ADZ. Furthermore, we revealed that treatment discontinuation following chronic ADZ administration (3 and 6 mg/kg) caused several somatic withdrawal symptoms in mice, including body tremor. Moreover, it induced motivational withdrawal signs, such as anxiety-related behavior in the elevated plus maze (EPM) test and memory deficits in the Y-maze test. After the IVSA test, an enzyme-linked immunosorbent assay (ELISA) showed that ADZ administration significantly increased the dopamine contents in the thalamus, nucleus accumbens (NAc), and ventral tegmental area (VTA). This finding was also supported by the results of the Western blot. Taken together, our results suggest that ADZ has abuse potential and can lead to drug dependence and withdrawal syndrome.

The relationship between long-term use of nonsteroidal anti-inflammatory drugs and kidney function in patients with ankylosing spondylitis.

Objective: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for ankylosing spondylitis (AS), their effect on kidney function remains unclear. This longitudinal study investigated the correlation between long-term NSAID use and kidney function in patients with AS using electronic medical records. Methods: The electronic medical records of 1,280 patients with AS collected from a single center between January 2001 and December 2018 were reviewed. The Assessment of Spondyloarthritis International Society (ASAS) NSAID Intake Score was used to determine the cumulative dose of all NSAIDs prescribed for a different time intervals. Each ASAS NSAID Intake Score was obtained for intervals of 6 months, 1 year, 2 years, 3 years, 5 years, and 10 years. The correlation between the ASAS NSAID Intake Score and final estimated glomerular filtration rate (eGFR) for each interval was investigated. Results: The mean ASAS Intake Scores for 6-month, 1-year, 2-year, 3-year, 5-year, and 10-year intervals were 55.30, 49.28, 44.84, 44.14, 44.61, and 41.17, respectively. At each interval, the pearson correlation coefficients were -0.018 (95% CI -0.031 to -0.006, p=0.004), -0.021 (95% CI -0.039 to -0.004, p=0.018), -0.045 (95% CI -0.071 to -0.019, p=0.001), -0.069 (95% CI -0.102 to -0.037, p<0.001), -0.070 (95% CI -0.114 to -0.026, p=0.002), -0.019 (95% CI -0.099 to 0.062, p=0.645), respectively. There was a very weak negative relationship between ASAS Intake Score and eGFR at each interval. Conclusion: Long-term NSAID use did not correlate with kidney function based on real-world data in patients with AS.

Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System.

2-(2,5-Dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)_ethanamine (25D-NBOMe), an analogue of the 2C family, is a newly synthesized psychoactive substance. It acts as an agonist at the 5-HT2A receptor and has a similar mechanism to that of NBOMe compounds. However, the pharmacological mechanism for its rewarding and reinforcing effects has not been revealed. In the present study, intravenous self-administration (IVSA) test and conditioned place preference (CPP) test were performed to investigate whether 25D-NBOMe has abuse potential. We also evaluated the effects of 25D-NBOMe on neurochemical changes using western blot analysis and microdialysis. The IVSA test revealed increased self-administration in 25D-NBOMe (0.03 mg/kg)-treated rats. In addition, the CPP test revealed rewarding effects in 25D-NBOMe (1 mg/kg)-treated mice. In the neurochemical studies, 25D-NBOMe treatment affected the expression of dopamine (DA) receptor D1 (DRD1), DA receptor D2 (DRD2), tyrosine hydroxylase, DA transporter (DAT), and phospho-DAT (p-DAT) in the nucleus accumbens (NAc). In addition, microdialysis revealed that treatment with progressively increasing doses (1, 3, and 10 mg/kg) of 25D-NBOMe increased the extracellular levels of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the rat NAc. Taken together, our results show the abuse potential and neurochemical changes related to addictive behavior after administration of 25D-NBOMe.

Prognostic significance of albuminuria in elderly of various ages with diabetes.

It remains uncertain whether albuminuria can identify elderly patients with diabetes at a high risk of incident end-stage kidney disease (ESKD) or mortality. 3065 patients (aged ≥ 65 years) with type 2 diabetes were included. We examined the association between albuminuria stages (normoalbuminuria, A1; microalbuminuria, A2; and macroalbuminuria, A3) and the risk of incident ESKD and all-cause mortality for each age group (65-69, 70-74, and ≥ 75 years). A2 and A3 were observed in 25.5% and 9.4% of the subjects, respectively. For A1, A2, and A3, the probabilities of ESKD at 8 years were 1.0%, 6.3%, and 29.7% (P < 0.001 for all), and the all-cause mortality was 13.1%, 27.4%, and 31.7% (P < 0.001 for A1 vs A2, P < 0.001 for A1 vs A3), respectively. Albuminuria stages were independently associated with an increased risk of ESKD [fully adjusted hazard ratios (HR): 3.650 (1.987-6.702) for A2, 10.404 (5.706-18.972) for A3 vs. A1]. The HRs of all-cause mortality were 1.742 (1.411-2.153) for A2 and 1.810 (1.344-2.441) for A3. The associations between albuminuria stages and the risk of ESKD and all-cause mortality were consistent across all age groups. Even microalbuminuria is also a risk factor for incident ESKD and mortality in elderly patients with diabetes.

Diagnostic accuracy of cardiovascular magnetic resonance strain analysis and atrial size to identify heart failure with preserved ejection fraction.

Aims: Heart failure with preserved ejection fraction (HFpEF) continues to be a diagnostic challenge. Cardiac magnetic resonance atrial measurement, feature tracking (CMR-FT), tagging has long been suggested to diagnose HFpEF and potentially complement echocardiography especially when echocardiography is indeterminate. Data supporting the use of CMR atrial measurements, CMR-FT or tagging, are absent. Our aim is to conduct a prospective case-control study assessing the diagnostic accuracy of CMR atrial volume/area, CMR-FT, and tagging to diagnose HFpEF amongst patients suspected of having HFpEF. Methods and results: One hundred and twenty-one suspected HFpEF patients were prospectively recruited from four centres. Patients underwent echocardiography, CMR, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements within 24 h to diagnose HFpEF. Patients without HFpEF diagnosis underwent catheter pressure measurements or stress echocardiography to confirm HFpEF or non-HFpEF. Area under the curve (AUC) was determined by comparing HFpEF with non-HFpEF patients. Fifty-three HFpEF (median age 78 years, interquartile range 74-82 years) and thirty-eight non-HFpEF (median age 70 years, interquartile range 64-76 years) were recruited. Cardiac magnetic resonance left atrial (LA) reservoir strain (ResS), LA area index (LAAi), and LA volume index (LAVi) had the highest diagnostic accuracy (AUCs 0.803, 0.815, and 0.776, respectively). Left atrial ResS, LAAi, and LAVi had significantly better diagnostic accuracy than CMR-FT left ventricle (LV)/right ventricle (RV) parameters and tagging (P < 0.01). Tagging circumferential and radial strain had poor diagnostic accuracy (AUC 0.644 and 0.541, respectively). Conclusion: Cardiac magnetic resonance LA ResS, LAAi, and LAVi have the highest diagnostic accuracy to identify HFpEF patients from non-HFpEF patients amongst clinically suspected HFpEF patients. Cardiac magnetic resonance feature tracking LV/RV parameters and tagging had low diagnostic accuracy to diagnose HFpEF.

Impact of Renal Replacement Therapy on Mortality and Renal Outcomes in Critically Ill Patients with Acute Kidney Injury: A Population-Based Cohort Study in Korea between 2008 and 2015.

The outcomes depending on the type of renal replacement therapy (RRT) or pre-existing kidney disease in critically ill patients with acute kidney injury (AKI) have not been fully elucidated. All adult intensive care unit patients with AKI in Korea from 2008 to 2015 were screened. A total of 124,182 patients, including 21,165 patients with pre-existing kidney disease, were divided into three groups: control (no RRT), dialysis, and continuous RRT (CRRT). In-hospital mortality and progression to end-stage kidney disease (ESKD) were analyzed according to the presence of pre-existing kidney disease. The CRRT group had a higher risk of in-hospital mortality. Among the patients with pre-existing kidney disease, the dialysis group had a lower risk of in-hospital mortality compared to other groups. The risk of ESKD was higher in the dialysis and CRRT groups compared to the control group. In the CRRT group, the risk of ESKD was even higher in patients without pre-existing kidney disease. Although both dialysis and CRRT groups showed a higher incidence of ESKD, in-hospital mortality was lower in the dialysis group, especially in patients with pre-existing kidney disease. Our study supports that RRT and pre-existing kidney disease may be important prognostic factors for overall and renal outcomes in patients with AKI.

Role of Recent Therapeutic Applications and the Infection Strategies of Shiga Toxin-Producing Escherichia coli.

Shiga toxin-producing Escherichia coli (STEC) is a global foodborne bacterial pathogen that is often accountable for colon disorder or distress. STEC commonly induces severe diarrhea in hosts but can cause critical illnesses due to the Shiga toxin virulence factors. To date, there have been a significant number of STEC serotypes have been evolved. STECs vary from nausea and hemorrhoid (HC) to possible lethal hemolytic-based uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP). Inflammation-based STEC is usually a foodborne illness with Shiga toxins (Stx 1 and 2) thought to be pathogenesis. The STEC's pathogenicity depends significantly on developing one or more Shiga toxins, which can constrain host cell protein synthesis leading to cytotoxicity. In managing STEC infections, antimicrobial agents are generally avoided, as bacterial damage and discharge of accumulated toxins are thought the body. It has also been documented that certain antibiotics improve toxin production and the development of these species. Many different groups have attempted various therapies, including toxin-focused antibodies, toxin-based polymers, synbiotic agents, and secondary metabolites remedies. Besides, in recent years, antibiotics' efficacy in treating STEC infections has been reassessed with some encouraging methods. Nevertheless, the primary role of synbiotic effectiveness (probiotic and prebiotic) against pathogenic STEC and other enteropathogens is less recognized. Additional studies are required to understand the mechanisms of action of probiotic bacteria and yeast against STEC infection. Because of the consensus contraindication of antimicrobials for these bacterial pathogens, the examination was focused on alternative remedy strategies for STEC infections. The rise of novel STEC serotypes and approaches employed in its treatment are highlighted.

Different Seasonal Variations of Potassium in Hemodialysis Patients with High Longitudinal Potassium Levels: A Multicenter Cohort Study Using DialysisNet.

PURPOSE: To determine seasonal variations in serum potassium levels among hemodialysis patients. MATERIALS AND METHODS: This was a multicenter cohort study of patients whounderwent hemodialysis and were registered in DialysisNet at our four associated general hospitals between January and December 2016. Month-to-month potassium variability was quantified as SD/√{n/(n-1)}, and a non-hierarchical method was used to cluster groups according to potassium trajectories. Seasonal variations in potassium levels were analyzed using a cosinor analysis. RESULTS: The analysis was performed on 279 patients with a mean potassium level of 5.08±0.58 mmol/L. After clustering, 52.3% (n=146) of patients were included in the moderate group (K+, 4.6±0.4 mmol/L) and 47.7% (n=133) in the high group (K+, 5.6±0.4 mmol/L). The mean potassium level peaked in January in the moderate group (4.83±0.74 mmol/L) and in August in the high group (5.51±0.70 mmol/L). In the high potassium group, potassium levels were significantly higher in summer than in autumn (p<0.001) and spring (p=0.007). Month-to-month potassium variability was greater in the high group than in the moderate group (0.59±0.19 mmol/L vs. 0.52±0.21 mmol/L, respectively, p=0.012). Compared to patients in the first quartile of potassium variability (≤0.395 mmol/L), those with higher variability (2nd-4th quartiles) were 2.8-4.2 fold more likely to be in the high potassium group. CONCLUSION: Different seasonal patterns of serum potassium were identified in the moderate and high potassium groups, with potassium levels being significantly higher in the summer season in the high potassium group and in winter for the moderate potassium group.

Review on Stress Tolerance in Campylobacter jejuni.

Campylobacter spp. are the leading global cause of bacterial colon infections in humans. Enteropathogens are subjected to several stress conditions in the host colon, food complexes, and the environment. Species of the genus Campylobacter, in collective interactions with certain enteropathogens, can manage and survive such stress conditions. The stress-adaptation mechanisms of Campylobacter spp. diverge from other enteropathogenic bacteria, such as Escherichia coli, Salmonella enterica serovar Typhi, S. enterica ser. Paratyphi, S. enterica ser. Typhimurium, and species of the genera Klebsiella and Shigella. This review summarizes the different mechanisms of various stress-adaptive factors on the basis of species diversity in Campylobacter, including their response to various stress conditions that enhance their ability to survive on different types of food and in adverse environmental conditions. Understanding how these stress adaptation mechanisms in Campylobacter, and other enteric bacteria, are used to overcome various challenging environments facilitates the fight against resistance mechanisms in Campylobacter spp., and aids the development of novel therapeutics to control Campylobacter in both veterinary and human populations.

Creatinine- and cystatin C-based estimated glomerular filtration rate slopes for the prediction of kidney outcome: a comparative retrospective study.

BACKGROUND: Many studies have evaluated the usefulness of creatinine- (eGFRcr) and cystatin C-based estimated glomerular filtration rate (eGFRcys) at specific time points in predicting renal outcome. This study compared the performance of both eGFR changing slopes in identifying patients at high risk of end-stage renal disease (ESRD). METHODS: From 2012 to 2017, patients with more than three simultaneous measurements of serum creatinine and cystatin C for 1 year were identified. Rapid progression was defined as eGFR slope < - 5 mL/min/1.73 m2/year. The primary outcome was progression to ESRD. RESULTS: Overall, 1323 patients were included. The baseline eGFRcr and eGFRcys were 39 (27-48) and 38 (27-50) mL/min/1.73 m2, respectively. Over 2.9 years (range, 2.0-3.8 years) of follow-up, 134 subjects (10%) progressed to ESRD. Both the eGFRcr and eGFRcys slopes were associated with a higher risk of ESRD, independently of baseline eGFR (hazard ratio [HR] = 0.986 [0.982-0.991] and HR = 0.988 [0.983-0.993], respectively; all p <  0.001). The creatinine- and cystatin C-based rapid progressions were associated with increased risk of ESRD (HR = 2.22 [1.57-3.13], HR = 2.03 [1.44-2.86], respectively; all p <  0.001). In the subgroup analyses, the rapid progression group, defined on the basis of creatinine levels (n = 503), showed no association between the eGFRcys slope and ESRD risk (p = 0.31), whereas the eGFRcr slope contributed to further discriminating higher ESRD risk in the subjects with rapid progression based on eGFRcys slopes (n = 463; p = 0.003). CONCLUSIONS: Both eGFR slopes were associated with future ESRD risk. The eGFRcr slope was comparable with the eGFRcys slope in predicting kidney outcome.

The Role of Transcription Factors and Nuclear Pore Proteins in Controlling the Spatial Organization of the Yeast Genome.

Loss of nuclear pore complex (NPC) proteins, transcription factors (TFs), histone modification enzymes, Mediator, and factors involved in mRNA export disrupts the physical interaction of chromosomal sites with NPCs. Conditional inactivation and ectopic tethering experiments support a direct role for the TFs Gcn4 and Nup2 in mediating interaction with the NPC but suggest an indirect role for factors involved in mRNA export or transcription. A conserved "positioning domain" within Gcn4 controls interaction with the NPC and inter-chromosomal clustering and promotes transcription of target genes. Such a function may be quite common; a comprehensive screen reveals that tethering of most yeast TFs is sufficient to promote targeting to the NPC. While some TFs require Nup100, others do not, suggesting two distinct targeting mechanisms. These results highlight an important and underappreciated function of TFs in controlling the spatial organization of the yeast genome through interaction with the NPC.

Changes in acute kidney injury epidemiology in critically ill patients: a population-based cohort study in Korea.

BACKGROUND: Although no specific treatment facilitates renal tubular regeneration in acute kidney injury (AKI), the rapid increase in aging populations with more comorbidities and advances in critical care management are expected to change the epidemiology of AKI. However, few recent studies dissected the current epidemiologic characteristics of critically ill patients with AKI. We investigated recent epidemiologic changes in severe AKI in critically ill patients. METHODS: All adult admissions to intensive care units (ICUs) in Korea from 2008 to 2015 were screened using the national health insurance review and assessment database, and 1,744,235 patients were included. Clinical characteristics and changes in AKI incidence and mortality rate were analyzed. RESULTS: The incidence of AKI increased from 7.4% in 2008 to 8.3% in 2015 (p for trend < 0.001). Age-standardized AKI rate was 7018.6 per 100,000 person-years. In-hospital mortality significantly decreased from 39.1% in 2008 to 37.2% in 2015 (p for trend < 0.001) with 2427.6 deaths per 100,000 person-years. Patients with AKI showed higher in-hospital mortality, prolonged ICU length of stay, and higher total cost. Multivariable analysis showed increased risk of in-hospital mortality (adjusted odds ratio [OR] 3.74), mechanical ventilation (OR 2.87), ECMO (OR 6.99), and vasopressor requirement (OR 2.75) in patients with AKI. CONCLUSIONS: Recent advances in medical management for AKI have improved in-hospital mortality of critically ill patients with AKI despite increases in the elderly population and AKI incidence.

Arteriovenous graft patency outcomes and prognostic factors.

OBJECTIVES: Arteriovenous graft for hemodialysis shows poorer outcomes than arteriovenous fistula, due to frequent stenosis and thrombosis. We investigated arteriovenous graft patency outcomes and prognostic factors for these outcomes. METHODS: We included a single-center cohort of patients receiving arteriovenous graft for hemodialysis access from 2010 to 2014. Demographics, laboratory data, comorbidities, and medications were collected from medical records. Surgical factors related to graft operation including the type and diameter of connected vessels, graft location, and type of operation (elective or emergency) were also recorded. Outcomes included primary and secondary patency. Survival analysis was conducted using the Kaplan-Meier method; univariate and multivariate analyses were used to evaluate the prognostic factors. RESULTS: Data from 225 grafts were analyzed. During the follow-up period (mean: 583 days, range: 1-1717 days), 138 (61%) grafts required intervention and 46 (20%) permanently failed. Primary patency at one, two, and three years was 42%, 20%, and 16%, respectively. Secondary patency at one, two, and three years was 85%, 72%, and 64%, respectively. Multivariate analysis showed that primary patency was negatively associated with increasing age and location of vessel anastomosis (reference-brachiobrachial anastomosis; brachiobasilic - HR, 0.569; 95% CI, 0.376-0.860; p = 0.007; brachioaxillary anastomosis - HR 0.407; 95% CI, 0.263-0.631; p < 0.0001); secondary patency was positively associated with diastolic blood pressure, serum albumin level, and hemoglobin over 10 g/dL. Adverse events other than stenosis or thrombosis, such as infection/inflammation or pseudoaneurysm were observed in approximately 20% of grafts. CONCLUSIONS: Factors associated with diminished primary arteriovenous graft patency included increased patient age and location of vessel anastomosis (brachiobrachial type compared to brachiobasilic or brachioaxillary type); diminished secondary patency was associated with low diastolic blood pressure, low serum albumin, and hemoglobin level under 10 g/dL. Among these factors, diastolic blood pressure, serum albumin, and hemoglobin level may be modifiable and could improve arteriovenous graft patency outcomes.

The ratio of urinary sodium and potassium and chronic kidney disease progression: Results from the KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD).

The Na/K ratio in urine stands for the dietary of sodium and potassium intake in patients with chronic kidney disease remains unclear for the renal progression. We aimed to determine the risk of progression of chronic kidney disease based on the Na/K ratio in a 24-hour urine collection.We determined the association between the progression of renal disease and 24-hour urinary sodium and potassium (Na/K) ratios in 2238 patients over a 5-year timespan using data obtained from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD). Renal events were defined as a 50% decrease in the glomerular filtration rate (GFR) below baseline, or the onset of end-stage renal disease (ESRD). Patients were divided into 4 groups based on the quartile range of the 24-hour urinary sodium and potassium ratio. We analyzed those variables in the 4 groups. Multiple logistic regression analyses were performed using the data of 1001 patients to identify the independent factors associated with renal events.Age and male sex accounted for the greatest number of patients in the group with the highest values (group 4) of the 24-hour urinary Na/K ratio (≥3.85). There was no difference in the prevalence of hypertension or diabetes mellitus, the ratio of use of antihypertensive drugs, blood pressures, or estimated GFRs. In the group with the highest urinary Na/K ratio, the 24-hour urinary Na concentration mean ±â€Šstandard deviation was 188.7 ±â€Š70.6 mmol and that of urinary K was 39.9 ±â€Š16.1 mmol. The urinary protein excretion was highest in the group with the highest urinary Na/K ratio. In the logistic regression analysis, the effect on renal events increased with increasing urinary Na/K ratios. After adjusting for other factors, the risk of renal events was 2.48 (95% confidence interval (CI) 1.30-4.90) in group 3, and 3.75 (95% CI: 1.35-11.27) in group 4. In the Kaplan-Meier analysis, the higher the urinary Na/K ratio, the higher the rate of CKD progression.Based on our analyses, we concluded that the higher the urinary Na/K ratio, the greater the risk of CKD progression.

In vitro and in vivo defensive effect of probiotic LAB against Pseudomonas aeruginosa using Caenorhabditis elegans model.

This study aimed to investigate in vitro and in vivo the probiotic characteristics of lactic acid bacteria (LAB) isolated from Korean traditional fermented foods. Caenorhabditis elegans  (C. elegans) was used for analytical assays of fertility, chemotaxis, life-span, worm-killing and bacterial colonization in the intestinal lumen of the worm. All 35 strains of LAB reduced fertility and slowed development in the worms. The worm-killing assay showed that LAB significantly increased the lifespan (P < 0.05) and reduced the susceptibility to virulent PA14; however, the heat-killed LAB did not. The bacterial colonization assay revealed that LAB proliferated and protected the gut of the worm against infection by Pseudomonas aeruginosa PA14. In addition, specific LAB Pediococcus acidilactici(P. acidilactici DM-9), Pediococcus brevis (L. brevis SDL1411), and Pediococcus pentosaceus (P. pentosaceus SDL1409) strains showed acid resistance (66-91%), resistance to pepsin (64-67%) and viability in simulated intestinal fluid (67-73%) based on in vitro probiotic analyses. Taken together, these results suggest that C. elegans may be a tractable model for screening efficient probiotics.

Ten-year observational follow-up of a randomized trial comparing cyclosporine and tacrolimus therapy combined with steroid withdrawal in living-donor renal transplantation.

Although various strategies for steroid withdrawal after transplantation have been attempted, there are few reports of the long-term results of steroid withdrawal regimens in kidney transplantation. Earlier, we reported on a 5-year prospective, randomized, single-center trial comparing the safety and efficacy of cyclosporine (CsA) plus mycophenolate mofetil (MMF) with that of tacrolimus (TAC) plus MMF, when steroids were withdrawn 6 months after kidney transplantation in low-risk patients. We now report the 10-year observational data on the study population. We collected data from the database of the Organ Transplantation Center, Samsung Medical Center for 5 years after completion of the original study (TAC group n = 62; CsA group n = 55). The 10-year patient survival, death-censored graft survival, and acute rejection-free survival did not differ between groups (98% vs 96%; P = 0.49, 78% vs 85%; P = 0.75 and 84% vs 76%; P = 0.14 in the TAC group vs CsA group, respectively). In low-risk patients, there was no difference in long-term patient and graft survival between TAC- and CsA-based late steroid withdrawal regimens that included MMF treatment. More long-term randomized clinical trials are needed to clarify the benefits of late steroid withdrawal in kidney transplantation.

Variation in the rate of well-controlled status of chronic disease by income level in Korea: 2010 to 2015.

Although it is known that the prevalence rates of chronic diseases depend on income level, annual changes of the control rate have not been evaluated. In this cross-sectional study, we analyzed the variation in rate of well-controlled status of chronic diseases based on the annual income level using data from national nutrition surveys conducted between 2010 and 2015.Prevalence and controlled rate of hypertension, diabetes mellitus, and chronic kidney disease were analyzed in relation to annual income levels, using data from the Korea National Health and Nutrition Examination Survey (KNHANES), obtained from 2010 to 2015. We also analyzed the incidence of use of necessary medical care services and the reasons cited for not using these services.The data of 28,759 persons were analyzed. The average age increased, and sex ratio remained unchanged over the study period. Although the prevalence rates of diabetes increased, that of increased glycated hemoglobin gradually decreased. A significant change has been shown recently on the prevalence rates of hypertension patients. The prevalence rates of chronic kidney disease stayed unchanged during the course of the study period. The incidence of controlled chronic disease status increased with the income level, and over time during the study, in the case of diabetes and chronic kidney disease. However, while controlled hypertension status rate increased from year to year, there was no trend of increase with increased income level. The incidence of participants not using hospital services declined with increasing income level, but the rate of economic causes being cited as reasons for not using hospital services increased over time and showed no change among income levels. Results of regression analysis of prevalence rates of chronic diseases by income level showed that lower income groups tended to have higher odds ratios for chronic diseases.Our results suggest that the incidence rate of well-controlled chronic disease status remains low in lower income groups. These results imply that financial status may play an important role in the management of chronic diseases.

First-year GFR slope and long-term renal outcome in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most frequent primary glomerular disease and the leading cause of end-stage renal disease. We investigated clinicopathologic predictors of renal survival in patients with IgAN with a focus on glomerular filtration rate (GFR) decline slope. MATERIALS AND METHODS: We screened all patients with primary IgAN between 1995 and 2012. Renal progression was defined as doubling of serum creatinine. Using serial serum creatinine levels during the first-year, we calculated the GFR decline slopes. Further, we defined patients in the steepest GFR slope quartile as rapid decliners and those in the second steepest GFR slope quartile as slow decliners. Others were defined as nondecliners. RESULTS: Of 214 participants, baseline GFR was 81 (62, 100) mL/min/1.73 m2 , which was not different among the 3 groups. Rapid decliners and slow decliners had higher levels of urinary protein/creatinine ratio (0.88, 0.89 and 0.58 g/gCr, respectively, P < .001). Five-year renal survival was 76% in rapid decliners, 91% in slow decliners and 100% in nondecliners (P < .001, rapid or slow decliners vs nondecliners). After adjustment for clinicopathologic variables, slow decliners were associated with an 8.8-fold higher risk of progression (P = .011), and rapid decliners were associated with a 10.2-fold increased risk of progression (P = .007) compared with nondecliners. CONCLUSIONS: First-year GFR slope was associated with increased risk of renal progression, independent of proteinuria and histologic findings. Further studies are needed to investigate whether early GFR change can identify high-risk patients who benefit from immunosuppressive treatment in IgAN.

In vivo screening platform for shiga toxin-producing Escherichia coli (STEC) using Caenorhabditis elegans as a model.

Shiga toxin-producing Escherichia coli (STEC) strains are the main cause of bacillary dysentery, although STEC strains generally induce milder disease symptoms compared to Shigella species. This study aimed to determine the virulence of STEC using the nematode Caenorhabditis elegans as a model host. Worm killing, fertility and bacterial colonisation assays were performed to examine the potential difference in the virulence of STEC strains compared to that of the control E. coli OP50 strains on which worms were fed. A statistically significant difference in the survival rates of C. elegans was observed in that the STEC strains caused death in 8-10 days and the E. coli OP50 strains caused death in 15 days. STEC strains severely reduced the fertility of the worms. The intestinal load of bacteria in the adult stage nematodes harbouring the E. coli OP50 strains was found to be 3.5 log CFU mL-1. In contrast, the STEC strains E15, E18 and E22 harboured 4.1, 4.2 and 4.7 log CFU ml-1 per nematode, respectively. The heat-killed STEC strains significantly increased the longevity of the worms compared to the non-heated STEC strains. In addition, PCR-based genomic profiling of shiga toxin genes, viz., stx1 and stx2, identified in selected STEC strains revealed that these toxins may be associated with the virulence of the STEC strains. This study demonstrated that C. elegans is an effective model to examine and compare the pathogenicity and virulence variation of STEC strains to that of E. coli OP50 strains.