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 (BMI ≥30 kg/m2), type 2 diabetes (T2DM), and baseline estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m² who underwent metabolic bariatric surgery at a large U.S. health system (2010-2017) were compared with nonsurgical patients who continuously received GLP-1RA. The primary end point was CKD progression, defined as decline of eGFR by ≥50% or to <15 mL/min/1.73 m2, initiation of dialysis, or kidney transplant. The secondary end point was the incident kidney failure (eGFR <15 mL/min/1.73 m2, 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, 27.7-58.4) in the nonsurgical group, with an adjusted hazard ratio of 0.40 (95% CI, 0.21-0.76), P=0.006. The cumulative incidence of the secondary composite end point at 8-years was 24.0% (95% CI, 14.1-33.2) in the surgical group and 43.8% (95% CI, 28.1-56.1) in the nonsurgical group, with an adjusted HR of 0.56 (95% CI, 0.31-0.99), P=0.048. CONCLUSIONS: Among patients with T2DM, 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.

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.

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.

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.

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.

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.

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.

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.

Ribonucleotide reductase subunit M2 predicts survival in subgroups of patients with non-small cell lung carcinoma: effects of gender and smoking status.

BACKGROUND: Ribonucleotide reductase catalyzes the conversion of ribonucleotide diphosphates to deoxyribonucleotide diphosphates. The functional enzyme consists of two subunits - one large (RRM1) and one small (RRM2 or RRM2b) subunit. Expression levels of each subunit have been implicated in prognostic outcomes in several different types of cancers. EXPERIMENTAL DESIGN: Immunohistochemistry for RRM1 and RRM2 was performed on a lung cancer tissue microarray (TMA) and analyzed. 326 patients from the microarray were included in this study. RESULTS: In non-small cell lung cancer (NSCLC), RRM2 expression was strongly predictive of disease-specific survival in women, non-smokers and former smokers who had quit at least 10 years prior to being diagnosed with lung cancer. Higher expression was associated with worse survival. This was not the case for men, current smokers and those who had stopped smoking for shorter periods of time. RRM1 was not predictive of survival outcomes in any subset of the patient group. CONCLUSION: RRM2, but not RRM1, is a useful predictor of survival outcome in certain subsets of NSCLC patients.

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.

Ultrasound and modulation assisted synthesis of {[Cu2(BDC-NH2)2(dabco)]DMF.3H2O} nanostructures: new precursor to prepare nanorods and nanotubes of copper(II) oxide.

Nanostructures of porous coordination polymer {[Cu2(BDC-NH2)2(dabco)]DMF.3H2O} (1) have been synthesized in the presence of acetic acid as a modulator via sonochemical method. Different concentrations of metal ions, organic linkers, modulator reagent and also different sonication times were held to improve the quality and distribution of nanostructures. Ultrasound irradiation helps to nucleation step of the oriented attachment of modulation method and nanorods of compound 1 has been prepared. Compound 1 was calcinated at 500°C to prepare nanorods and nanotubes of copper(II) oxide. Compound 1 and CuO nanostructures were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high resolution transmission electron microscopy (HR-TEM), X-ray powder diffraction (XRD) and thermal gravimetric analysis (TGA).

Ultrasound assisted synthesis of {[Cu2(BDC)2(dabco)].2DMF.2H2O} nanostructures in the presence of modulator; new precursor to prepare nano copper oxides.

As a new precursor to prepare nano copper oxide, nanostructures of porous metal organic framework (MOF) {[Cu2(BDC)2(dabco)].2DMF.2H2O} (1) have been synthesized in the presence of acetic acid as a modulator via sonochemical method. Different concentrations of metal ion, organic linkers, modulator reagent and also different sonication times were held to improve the quality of nanostructures. Ultrasound irradiation helps nucleation step of the oriented attachment of modulation method and nanoparticles with a few nanorods has been prepared. As prepared MOF was calcinated at 500 °C to prepare nano CuO and Cu2O. Compound 1, CuO and Cu2O nanostructures were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray powder diffraction (XRD).

Pseudomonas aeruginosa induces pigment production and enhances virulence in a white phenotypic variant of Staphylococcus aureus.

Staphyloxanthin is a virulence factor which protects Staphylococcus aureus in stress conditions. We isolated two pigment variants of S. aureus and one strain of Pseudomonas aeruginosa from a single wound infection. S. aureus variants displayed white and yellow colony phenotypes. The sequence of the operons for staphyloxanthin synthesis indicated that coding and promoter regions were identical between the two pigment variants. Quorum sensing controls pigment synthesis in some bacteria. It is also shown that P. aeruginosa quorum-sensing molecules affect S. aureus transcription. We explored whether the co-infecting P. aeruginosa can affect pigment production in the white S. aureus variant. In co-culture experiments between the white variants and a selected number of Gram-positive and Gram-negative bacteria, only P. aeruginosa induced pigment production in the white variant. Gene expression analysis of the white variant did not indicate upregulation of the crtM and other genes known to be involved in pigment production (sigB, sarA, farnesyl pyrophosphate synthase gene [FPP-synthase], hfq). In contrast, transcription of the catalase gene was significantly upregulated after co-culture. P. aeruginosa-induced pigment synthesis and catalase upregulation correlated with increased resistance to polymyxin B, hydrogen peroxide, and the intracellular environment of macrophages. Our data indicate the presence of silent but functional staphyloxanthin synthesis machinery in a white phenotypic variant of S. aureus which is activated by a co-infecting P. aeruginosa via inter-species communication. Another S. aureus virulence factor, catalase is also induced by this co-infecting bacterium. The resulting phenotypic changes are directly correlated with resistance of the white variant to stressful conditions.

Assessment of Nutritional and Depression Status in Free-Living El-derly in Tabriz, Northwest Iran.

BACKGROUND: Malnutrition and depression are the common health problems in elderly population. Poor nutrition might have a strong effect on the incidence of depression. The aims of this study were to assess the nutritional and depression status and the possibly relationship between these variables in the urban free-liv-ing elderly in Tabriz, northwestern Iran. METHODS: This cross-sectional study was carried out on 184 elderly people (male=97; female=87) with age 60 years or elder in 2012. All subjects entered to the study voluntarily from those attending to daily care centers for elderly peo-ple. Mini Nutritional Assessment (MNA) tool and Geriatric Depression Score (GDS) were used to evaluate nutritional status and depression scores, respec-tively. Con-tinuous variables were expressed as mean ± standard deviation (SD) and qualita-tive data were presented as frequency (percent). Spearman's correla-tion was em-ployed to determine the relationship between variables. RESULTS: Up to 50% of subjects had poor nutrition status. About 14% of elderly people had serve depression and 28.3% had mild depression. There was a posi-tive significant correlation between MNA and GDS tests in both gender (r=0.416; P<0.001). CONCLUSION: There was no acceptable level of nutritional status and mental health in the elderly people. Further studies are needed to evaluate the other factors that can effect on the quality of life in this population.

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.

Progesterone and estrogen receptor expression and activity in human non-small cell lung cancer.

Lung cancer is the most common cause of cancer mortality in male and female patients in the US. Although it is clear that tobacco smoking is a major cause of lung cancer, about half of all women with lung cancer worldwide are never-smokers. Despite a declining smoking population, the incidence of non-small cell lung cancer (NSCLC), the predominant form of lung cancer, has reached epidemic proportions particularly in women. Emerging data suggest that factors other than tobacco, namely endogenous and exogenous female sex hormones, have a role in stimulating NSCLC progression. Aromatase, a key enzyme for estrogen biosynthesis, is expressed in NSCLC. Clinical data show that women with high levels of tumor aromatase (and high intratumoral estrogen) have worse survival than those with low aromatase. The present and previous studies also reveal significant expression and activity of estrogen receptors (ERα, ERß) in both extranuclear and nuclear sites in most NSCLC. We now report further on the expression of progesterone receptor (PR) transcripts and protein in NSCLC. PR transcripts were significantly lower in cancerous as compared to non-malignant tissue. Using immunohistochemistry, expression of PR was observed in the nucleus and/or extranuclear compartments in the majority of human tumor specimens examined. Combinations of estrogen and progestins administered in vitro cooperate in promoting tumor secretion of vascular endothelial growth factor and, consequently, support tumor-associated angiogenesis. Further, dual treatment with estradiol and progestin increased the numbers of putative tumor stem/progenitor cells. Thus, ER- and/or PR-targeted therapies may offer new approaches to manage NSCLC.

Expression levels of estrogen receptor beta in conjunction with aromatase predict survival in non-small cell lung cancer.

Estrogen signaling pathways may play a significant role in the pathogenesis of non-small cell lung cancers (NSCLC) as evidenced by the expression of aromatase and estrogen receptors (ERα and ERß) in many of these tumors. Here we examine whether ERα and ERß levels in conjunction with aromatase define patient groups with respect to survival outcomes and possible treatment regimens. Immunohistochemistry was performed on a high-density tissue microarray with resulting data and clinical information available for 377 patients. Patients were subdivided by gender, age and tumor histology, and survival data was determined using the Cox proportional hazards model and Kaplan-Meier curves. Neither ERα nor ERß alone was predictor of survival in NSCLC. However, when coupled with aromatase expression, higher ERß levels predicted worse survival in patients whose tumors expressed higher levels of aromatase. Although this finding was present in patients of both genders, it was especially pronounced in women ≥ 65 years old, where higher expression of both ERß and aromatase indicated a markedly worse survival rate than that determined by aromatase alone. Expression of ERß together with aromatase has predictive value for survival in different gender and age subgroups of NSCLC patients. This predictive value is stronger than each individual marker alone. Our results suggest treatment with aromatase inhibitors alone or combined with estrogen receptor modulators may be of benefit in some subpopulations of these patients.