Renoprotective Effects of Metabolic Surgery Versus GLP1 Receptor Agonists on Progression of Kidney Impairment in Patients with Established Kidney Disease.

OBJECTIVE: To examine the renoprotective effects of metabolic surgery in patients with established chronic kidney disease (CKD). BACKGROUND: The impact of metabolic surgery compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with established CKD has not been fully characterized. METHODS: Patients with obesity (body mass index ≥30 kg/m 2 ), type 2 diabetes, and baseline estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m² who underwent metabolic bariatric surgery at a large US health system (2010-2017) were compared with nonsurgical patients who continuously received GLP-1RA. The primary end point was CKD progression, defined as a decline of eGFR by ≥50% or to <15 mL/min/1.73 m 2 , initiation of dialysis, or kidney transplant. The secondary end point was the incident kidney failure (eGFR <15 mL/min/1.73 m 2 , dialysis, or kidney transplant) or all-cause mortality. RESULTS: 425 patients, including 183 patients in the metabolic surgery group and 242 patients in the GLP-1RA group, with a median follow-up of 5.8 years (IQR, 4.4-7.6), were analyzed. The cumulative incidence of the primary end point at 8 years was 21.7% (95% CI: 12.2-30.6) in the surgical group and 45.1% (95% CI: 27.7 to 58.4) in the nonsurgical group, with an adjusted hazard ratio of 0.40 (95% CI: 0.21 to 0.76), P =0.006. The cumulative incidence of the secondary composite end point at 8 years was 24.0% (95% CI: 14.1 to 33.2) in the surgical group and 43.8% (95% CI: 28.1 to 56.1) in the nonsurgical group, with an adjusted HR of 0.56 (95% CI: 0.31 to 0.99), P =0.048. CONCLUSIONS: Among patients with type 2 diabetes, obesity, and established CKD, metabolic surgery, compared with GLP-1RA, was significantly associated with a 60% lower risk of progression of kidney impairment and a 44% lower risk of kidney failure or death. Metabolic surgery should be considered as a therapeutic option for patients with CKD and obesity.

Clinical outcomes of bariatric surgery in patients with obesity and idiopathic intracranial hypertension.

INTRODUCTION: Obesity is a major risk factor for idiopathic intracranial hypertension (IIH). Effective therapeutics for preventing disease progression and alleviating symptoms are limited. This study aims to examine the effects of bariatric surgery on clinical outcomes of IIH. METHODS: We retrospectively collected data from the medical record of 97 patients with obesity and an existing diagnosis of IIH who underwent primary bariatric surgery at the Cleveland Clinic health system in the USA between 2005 and 2023. Pre- and postoperative data on presence of symptoms and clinical markers of IIH (headaches, visual field defects, papilledema, visual symptoms), intracranial pressure, and usage of IIH medications were compared. RESULTS: A total of 97 patients (98% female, median age 46.7 years, median BMI 48.3 kg/m2) with IIH who underwent bariatric surgery including Roux-en-Y gastric bypass (n = 66, 68%), sleeve gastrectomy (n = 27, 27.8%), and gastric banding (n = 4, 4.1%) were analyzed. In a median follow-up time of 3.0 years, the median total weight loss was 24% (interquartile range, 13-33%). There was a significant improvement in headache, papilledema, visual field deficits, and visual symptoms after bariatric surgery. The mean lumbar opening pressure before and after bariatric surgery was 34.8 ± 8.2 cm CSF and 24.2 ± 7.6 cm CSF, respectively, with a mean reduction of 10.7 cm CSF (95% confidence interval, 4.7 to 16.6), p = 0.003. The dosage of acetazolamide and topiramate, as well as the number of medications taken for IIH, decreased significantly after bariatric surgery (p < 0.001). CONCLUSION: For patients who have obesity, bariatric surgery is a viable treatment modality for alleviation or improvement of symptoms of IIH.

SETDB1 accelerates tumourigenesis by regulating the WNT signalling pathway.

We investigated the oncogenic role of SETDB1, focusing on non-small cell lung cancer (NSCLC), which has high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry; 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p <0.0001). The percentage of positive cells and the intensity of staining increased significantly with increased grade of disease. Forced expression of SETDB1 in NSCLC cell lines enhanced their clonogenic growth in vitro and markedly increased tumour size in a murine xenograft model, while silencing (shRNA) SETDB1 in NSCLC cells slowed their proliferation. SETDB1 positively stimulated activity of the WNT-ß-catenin pathway and diminished P53 expression, resulting in enhanced NSCLC growth in vitro and in vivo. Our finding suggests that therapeutic targeting of SETDB1 may benefit patients whose tumours express high levels of SETDB1.

Modifications of miRNAs in intervertebral disc degeneration: a key to the future development of genetic-based therapies.

Intervertebral disc degeneration (IDD) is the main cause of low back pain, which is a healthcare concern associated with high social and economic burden. The current medical and surgical therapies are inadequate and ineffective. Several miRNAs have been identified that modulate (via up- or down-regulation) the pathogenesis of IDD through various signaling pathways. Understanding the nature of this regulation and their signaling pathways will enable researchers to manipulate miRNA regulation to develop miRNA-based therapies. The development of miRNA-based therapies opens a future window through which to decrease the IDD process or regenerate the intervertebral disc. In the near future, the obstacles associated with miRNA-based therapies will be overcome and these therapies will move from the bench to the bedside.

Effect of Dexmedotomdine hydrochloride (Percedex®) on functional outcome of patients with moderate and severe traumatic brain injury.

Traumatic brain injury (TBI) is considered among the leading causes of morbidity and mortality worldwide being associated with significant social and economic burden. The best sedative regimen in TBI patients is yet to be identified. This study was designed to determine the effects of dexmedotomdine hydrochloride (Percedex®, DEX) on functional outcome of patients with moderate and severe traumatic brain injury (TBI). This was a retrospective cohort study including patients with severe (3-8) and moderate (9-13) TBI referring to a level I trauma center. We studied two groups of patients, those receiving DEX or routine sedation regimen in neurointensive care unit (NICU). The main outcome measures were the Glasgow outcome scale extended (GOSE) at 3 and 6-month. We have also recorded ICU and hospital length of stay (LOS) and the tracheostomy rate. We included 138 patients in two study groups (each including 69). The baseline characteristics were comparable between groups. DEX was associated with lower LOS in hospital (p = 0.002) and NICU (p = 0.003). The GOSE was comparable between two study groups at 3 (p = 0.245) and 6-month (p = 0.497). Multivariate regression analysis revealed that after LOS of NICU and hospital stay adjustment, DEX group experienced significantly improved 6-month GOSE with the average improvement in score of 0.92 compared to the control group (p = 0.041). DEX administration in patients with moderate and severe TBI was associated with decreased NICU and hospital LOS and improved functional outcome at 6-month.

Na,K-ATPase is a target of cigarette smoke and reduced expression predicts poor patient outcome of smokers with lung cancer.

Diminished Na,K-ATPase expression has been reported in several carcinomas and has been linked to tumor progression. However, few studies have determined whether Na,K-ATPase function and expression are altered in lung malignancies. Because cigarette smoke (CS) is a major factor underlying lung carcinogenesis and progression, we investigated whether CS affects Na,K-ATPase activity and expression in lung cell lines. Cells exposed to CS in vitro showed a reduction of Na,K-ATPase activity. We detected the presence of reactive oxygen species (ROS) in cells exposed to CS before Na,K-ATPase inhibition, and neutralization of ROS restored Na,K-ATPase activity. We further determined whether Na,K-ATPase expression correlated with increasing grades of lung adenocarcinoma and survival of patients with smoking history. Immunohistochemical analysis of lung adenocarcinoma tissues revealed reduced Na,K-ATPase expression with increasing tumor grade. Using tissue microarray containing lung adenocarcinomas of patients with known smoking status, we found that high expression of Na,K-ATPase correlated with better survival. For the first time, these data demonstrate that CS is associated with loss of Na,K-ATPase function and expression in lung carcinogenesis, which might contribute to disease progression.

Protein expression based multimarker analysis of breast cancer samples.

BACKGROUND: Tissue microarray (TMA) data are commonly used to validate the prognostic accuracy of tumor markers. For example, breast cancer TMA data have led to the identification of several promising prognostic markers of survival time. Several studies have shown that TMA data can also be used to cluster patients into clinically distinct groups. Here we use breast cancer TMA data to cluster patients into distinct prognostic groups. METHODS: We apply weighted correlation network analysis (WGCNA) to TMA data consisting of 26 putative tumor biomarkers measured on 82 breast cancer patients. Based on this analysis we identify three groups of patients with low (5.4%), moderate (22%) and high (50%) mortality rates, respectively. We then develop a simple threshold rule using a subset of three markers (p53, Na-KATPase-ß1, and TGF ß receptor II) that can approximately define these mortality groups. We compare the results of this correlation network analysis with results from a standard Cox regression analysis. RESULTS: We find that the rule-based grouping variable (referred to as WGCNA*) is an independent predictor of survival time. While WGCNA* is based on protein measurements (TMA data), it validated in two independent Affymetrix microarray gene expression data (which measure mRNA abundance). We find that the WGCNA patient groups differed by 35% from mortality groups defined by a more conventional stepwise Cox regression analysis approach. CONCLUSIONS: We show that correlation network methods, which are primarily used to analyze the relationships between gene products, are also useful for analyzing the relationships between patients and for defining distinct patient groups based on TMA data. We identify a rule based on three tumor markers for predicting breast cancer survival outcomes.

Prediction of water quality parameters using machine learning models: a case study of the Karun River, Iran.

Accurate water quality predicting has an essential role in improving water management and pollution control. The machine learning models have been successfully implemented for modelling total dissolved solids (TDS), sodium absorption ratio (SAR) and total hardness (TH) content in aquatic ecosystems with insufficient data. However, due to multiple pollution sources and complex behaviours of pollutants, these models' effect in predicting TDS, SAR, and TH levels in the Karun River system is still unclear. Given this problem, multiple linear regression (MLR), M5P model tree, support vector regression (SVR) and random forest regression (RFR) models were used to predict TDS, SAR and TH variables in the four stations in the Karun River for 1999-2019 period. Initially, to reduce the number of input variables, the principal component analysis (PCA) technique was used. The developed models are valued in terms of the coefficient of determination (R2) and the root mean square error (RMSE). Base on the PCA, it was found that sodium (Na), chloride (Cl) and TH and Na and Cl are the most influential inputs on TDS and SAR, respectively, while calcium (Ca) and magnesium (Mg) are the most effective on TH. The results indicated that RFR, SVR and MLR models had the lowest error in predicting TDS, SAR and TH, respectively, in all stations. RFR model had the highest performance for predicting TDS (R2= 0.98, RMSE= 70.50 mg l-1), SVR model for predicting SAR (R2= 0.99, RMSE= 0.04) and MLR model for predicting TH (R2= 0.99, RMSE= 1.54 mg l-1) in Darkhovin station. The comparison of the results indicated that the machine learning models could satisfactorily estimate the TDS, SAR and TH for all stations.

Differential expression of anterior gradient gene AGR2 in prostate cancer.

BACKGROUND: The protein AGR2 is a putative member of the protein disulfide isomerase family and was first identified as a homolog of the Xenopus laevis gene XAG-2. AGR2 has been implicated in a number of human cancers. In particular, AGR2 has previously been found to be one of several genes that encode secreted proteins showing increased expression in prostate cancer cells compared to normal prostatic epithelium. METHODS: Gene expression levels of AGR2 were examined in prostate cancer cells by microarray analysis. We further examined the relationship of AGR2 protein expression to histopathology and prostate cancer outcome on a population basis using tissue microarray technology. RESULTS: At the RNA and protein level, there was an increase in AGR2 expression in adenocarcinoma of the prostate compared to morphologically normal prostatic glandular epithelium. Using a tissue microarray, this enhanced AGR2 expression was seen as early as premalignant PIN lesions. Interestingly, within adenocarcinoma samples, there was a slight trend toward lower levels of AGR2 with increasing Gleason score. Consistent with this, relatively lower levels of AGR2 were highly predictive of disease recurrence in patients who had originally presented with high-stage primary prostate cancer (P = 0.009). CONCLUSIONS: We have shown for the first time that despite an increase in AGR2 expression in prostate cancer compared to non-malignant cells, relatively lower levels of AGR2 are highly predictive of disease recurrence following radical prostatectomy.

Comparative effects of nano-selenium and sodium selenite supplementations on fertility in aged broiler breeder males.

It is well documented that aging has negative effects on fertility. With increasing age, the activity of antioxidant enzymes are reduced and because of roosters sperm composition, a high proportion of polyunsaturated fatty acids (PUFAs), the probability of sperm damage increases. The objective of the present study was to compare the effects of nano-selenium and sodium selenite on fertility in aged male broiler breeder chickens. Thirty-five male broiler breeders (Cobb 500)® at 50 weeks of age were randomly divided into five equal groups: The control group was fed on a commercial diet, group T1 was fed on a commercial diet supplemented with sodium selenite (0.30 mg kg-1 feed), group T2, T3 and T4 were fed on a commercial diet supplemented with nano-selenium (0.15, 0.30 and 0.60 mg kg-1 feed, respectively). Sperm characteristics (sperm count, motility, viability, and maturity) as well as testicular histomorphometric features [tubule differentiation (TDI), spermiation (SPI), Sertoli cell (SCI) and meiotic (MI) indices] were assessed. The results showed that sperm characteristics were gradually decreased with age in the control group, however, it increased in group T3. Also, TDI, SPI, SCI, and MI in group T3 were higher than those of other groups. Our findings revealed that dietary supplementations with nano-selenium boosted fertility in aged male broiler breeders and the best results were obtained when the roosters received 0.30 mg kg-1 nano-selenium. Supplementation of nano-selenium in aged broiler breeder males might be effective to maintain flock fertility and/or increase the flock fertility.

Intravenous Acetaminophen (Paracetamol) for Postcraniotomy Pain: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Acute pain control after supratentorial craniotomy is considered among the most important indicators of postoperative recovery. The aim of this study was to determine the effects of intravenous acetaminophen on postcraniotomy pain. METHODS: We searched databases including Embase, Scopus, Medline, Cochrane Library, and Web of Science until April 2019. Cochran Q test and I2 statistic were used to assess the heterogeneity across included clinical trials. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to estimate pooled effect sizes. RESULTS: Out of 479 reports, 5 randomized controlled trials met the inclusion criteria and were appropriate for our meta-analysis, which included a total of 2635 patients. The pooled results of included clinical trials indicated that paracetamol intake significantly decreased rescue dose (SMD, -0.67; 95% CI, -1.15 to -0.19; P < 0.01; I2 = 90.0%), total dosage of rescue (SMD, -0.78; 95% CI, -1.18 to -0.37; P < 0.01; I2 = 86.0%), intensive care unit length of stay (SMD, -0.24; 95% CI, -0.44 to -0.04; P = 0.01; I2 = 0.0%), and visual analog scale score (SMD, -0.16; 95% CI, -0.31 to -0.00; P = 0.04; I2 = 71.7%) and increased patient satisfaction (SMD, 0.28; 95% CI, 0.14-0.43; P < 0.01; I2 = 10.2%) among patients with craniotomy. Time to rescue (SMD, 0.21; 95% CI, -0.42 to 0.85; P = 0.51; I2 = 94.3%) and hospital length of stay (SMD, -0.04; 95% CI, -0.24 to 0.16; P = 0.69; I2 = 0.0%) did not significantly change after paracetamol intake. CONCLUSIONS: The results of this systematic review and meta-analysis indicate that preoperative intravenous administration of acetaminophen is associated with decreased postoperative pain, need for rescue analgesics, and dosages of analgesics after craniotomy surgery.

Draft Genome Sequence of Pseudomonas aeruginosa Strain LMG 1272, an Atypical White Line Reaction Producer.

The draft genome sequence of Pseudomonas aeruginosa LMG 1272, isolated from mushroom, is reported here. This strain triggers formation of a precipitate ("white line") when cocultured with Pseudomonas tolaasii However, LMG 1272 lacks the capacity to produce a cyclic lipopeptide that is typically associated with white line formation, suggesting the involvement of a different diffusible factor.

Syntheses of BaCO3 nanostructures by ultrasonic method.

BaCO3 nanostructures were synthesized by the reaction of Ba(CH3COO)2 and sodium hydroxide or tetramethylammonium hydroxide (TMAH) by a sonochemical method. Reaction conditions, such as the concentration of the Ba2+ ion, aging time and power of the ultrasonic device played important roles in the size, morphology and growth process of the final products. The BaCO3 nanostructures were characterized by scanning electron microscopy (SEM), X-ray powder diffraction (XRD), and the Infrared spectroscopy (IR).

Assessment of the northern distribution range of selected Perkinsus species in eastern oysters (Crassostrea virginica) and hard clams (Mercenaria mercenaria) with the use of PCR-based detection assays.

Perkinsus species are protistan parasites of molluscs. In Chesapeake Bay, Perkinsus marinus, Perkinsus chesapeaki, and Perkinsus andrewsi are sympatric, infecting oysters and clams. Although P. marinus is a pathogen for Crassostrea virginica, it remains unknown whether P. andrewsi and P. chesapeaki are equally pathogenic. Perkinsus species have been reported in C. virginica as far north as Maine, sometimes associated with high prevalence, but low mortality. Thus, we hypothesized that, in addition to P. marinus, Perkinsus species with little or no pathogenicity for C. virginica may be present. Accordingly, we investigated the distribution of Perkinsus species in C. virginica and Mercenaria mercenaria, collected from Maine to Virginia, by applying PCR-based assays specific for P. marinus, P. andrewsi, and a Perkinsus sp. isolated from M. mercenaria. DNA samples of M. mercenaria possessed potent PCR inhibitory activity, which was overcome by the addition of 1 mg/ml BSA and 5% (v/v) DMSO to the PCR reaction mixture. All 3 Perkinsus species were found in both host species throughout the study area. Interestingly, the prevalence of P. marinus in M. mercenaria was significantly lower than in C. virginica, suggesting that M. mercenaria is not an optimal host for P. marinus.

Comparative study of semen traits and histomorphometric features of testes of broiler breeder males with different phenotypic traits.

Fertility reduction due to sub-fertile males is a major concern in breeder flocks. Phenotypic traits of broiler breeder males and their relationships with fertility can be used as reliable indicators for identification and removal of sub-fertile males from the breeder flocks. This study was conducted to investigate semen traits (semen volume, sperm motility, sperm viability and sperm count) and testes histomorphometric features including tubule differentiation index (TDI), spermiation index (SPI), Sertoli cell index (SCI) and mitotic index (MI) of broiler breeder males with the same age but different phenotypic traits. According to phenotypic traits, 12 broiler breeder males (Ross-308 strain) were classified into three equal groups. Group 1: roosters with fertile phenotypic traits (fertile), group 2: roosters with the lowest fertile phenotypic traits (sub-fertile) and group 3: roosters with moderate fertile phenotypic traits (moderate). The results confirmed potential relationship between phenotypic traits and fertility in broiler breeder males. Semen traits and histomorphometric features of broiler breeder males' testis of the group 3 were more similar to those of the fertile roosters. Therefore, it can be concluded that exclusion of these roosters from the breeder flock may have undesirable effects on flock fertility.

Hemodynamics influences vascular peroxynitrite formation: Implication for low-density lipoprotein apo-B-100 nitration.

Hemodynamics, specifically, fluid shear stress, modulates the focal nature of atherogenesis. Superoxide anion (O2(-.)) reacts with nitric oxide (.NO) at a rapid diffusion-limited rate to form peroxynitrite (O2(-.) + .NO-->ONOO(-)). Immunohistostaining of human coronary arterial bifurcations or curvatures, where OSS develops, revealed the presence of nitrotyrosine staining, a fingerprint of peroxynitrite; whereas in straight segments, where PSS occurs, nitrotyrosine was absent. We examined vascular nitrative stress in models of oscillatory (OSS) and pulsatile shear stress (PSS). Bovine aortic endothelial cells (BAEC) were exposed to fluid shear stress that simulates arterial blood flow: (1) PSS at a mean shear stress (tau(ave)) of 23 dyn cm(-2) and a temporal gradient (partial differential(tau)/partial differential(t)) at 71 dyn cm(-2) s(-1), and (2) OSS at tau(ave) = 0.02 dyn cm(- 2) and partial differential(tau)/partial differential(t) = +/- 3.0 dyn cm(-2) s(-1) at a frequency of 1 Hz. OSS significantly up-regulated one of the NADPH oxidase subunits (NOx4) expression accompanied with an increase in O2(-.) production. In contrast, PSS up-regulated eNOS expression accompanied with .NO production (total NO(2)(-) and NO(3)(-)). To demonstrate that O2(-.) and .NO are implicated in ONOO(-) formation, we added low-density lipoprotein cholesterol (LDL) to the medium in which BAEC were exposed to the above flow conditions. The medium was analyzed for LDL apo-B-100 nitrotyrosine by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS). OSS induced higher levels of 3-nitrotyrosine, dityrosine, and o-hydroxyphenylalanine compared with PSS. In the presence of ONOO(-), specific apo-B-100 tyrosine residues underwent nitration in the alpha and beta helices: alpha-1 (Tyr(144)), alpha-2 (Tyr(2524)), beta-2 (Tyr(3295)), alpha-3 (Tyr(4116)), and beta-2 (Tyr(4211)). Hence, the characteristics of shear stress in the arterial bifurcations influenced the relative production of O2(-.) and .NO with an implication for ONOO(-) formation as evidenced by LDL protein nitration.

Effect of a resin-based desensitizing agent and a self-etching dentin adhesive on marginal leakage of amalgam restorations.

AIM: The purpose of this study was to compare the marginal leakage of Class II amalgam restorations whose preparations were lined with a resin-based desensitizing agent, a self-etching adhesive system, and copal varnish. METHODS AND MATERIALS: Fifty-six freshly extracted human premolar teeth were divided into four groups. A Class II preparation was prepared with only a proximal box on the mesial and distal surfaces of each tooth. The cavities in one group were lined with a desensitizing agent (VivaSens) and a second group with an adhesive (Clearfil S3 Bond). A third group was lined with copal varnish (Copalite) and a fourth group was used as the control without any cavity liner. Spherical high copper amalgam was hand-condensed into each preparation, specimens were thermocycled, stained, and sectioned. Microleakage was graded using a stereomicroscope. Microleakage scores were calculated and analyzed using the Kruskal Wallis and the Mann-Whitney tests (alpha=0.05). RESULTS: Less microleakage was indicated with the VivaSens liner when compared with the other groups (P<0.05). Clearfil S3 Bond showed less microleakage than the control group (P<0.05), but the leakage with copal varnish and Clearfil S3 Bond was similar (P>0.05). CONCLUSION: VivaSens reduced the microleakage of Class II high copper amalgam restorations significantly more than the Clearfil S3 Bond and copal varnish.