Recruiting African American Prostate Cancer Survivors for a Population-based Biobank Study.

BACKGROUND: Prostate cancer affects African American men disproportionately compared with men of other racial/ethnic groups. To identify biological bases for this health disparity, we sought to create a state-wide biobank of African American prostate cancer survivors in Florida. METHODS: African American men diagnosed with prostate cancer between 2013 and 2017 and living in Florida at diagnosis were identified through the State of Florida's cancer registry. Individuals were approached via mail and telephone, assessed for eligibility, and asked for informed consent. χ2 and t tests were conducted to identify differences between eligible and reachable individuals (i.e., had valid contact information) versus consented participants. RESULTS: Of the 5,960 eligible and reachable individuals, 3,904 were eligible and contacted at least once, and 578 consented [overall consent rate = 10% (578/5,960); adjusted consent rate = 15% (578/3,904)]. Statistically significant (Ps < 0.05) but small differences in demographic and clinical variables were observed. Consented participants were less likely to be older than 64 (35% vs. 41%) and less likely to have received radiotherapy (36% vs. 41%) and hormone therapy (16% vs. 21%), but more likely to have regional prostate cancer (13% vs. 11%) and have undergone surgery (44% vs. 39%). Consented participants did not differ from reachable individuals on other demographic and clinical factors (Ps > 0.05). CONCLUSIONS: Recruiting African American prostate cancer survivors to biobanking research through a cancer registry is feasible. However, the consent rate was low, and existing challenges limit consent and participation. IMPACT: Strategies for overcoming barriers to informed consent and increasing participation in biospecimen research are needed to address cancer disparities.

Translational Genomic Research: The Association between Genetic Profiles and Cognitive Functioning or Cardiac Function Among Breast Cancer Survivors Completing Chemotherapy.

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have "risk variants" in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.

Enterococcus faecalis promotes a migratory and invasive phenotype in colon cancer cells.

Much about the role of intestinal microbes at the site of colon cancer development and tumor progression following curative resection remains to be understood. We have recently shown that collagenolytic bacteria such as Enterococcus faecalis predominate within the colon postoperatively, particularly at the site of the colon reconnection (i.e. anastomosis) in the early period of post-surgical recovery. The presence of collagenolytic bacteria at this site correlates with the tumor progression in a mouse model of post-surgical tumor development. In the present study we hypothesized, that collagenolytic bacteria, such as E. faecalis, play an important yet to be discovered role in tumor formation and progression. Therefore the aims of this study were to assess the role of collagenolytic E. faecalis on the migration and invasion of a murine colon cancer cell line. Results demonstrated that both migration and invasion were induced by E. faecalis with collagenolytic activity being required for only invasion. Bidirectional signaling in the E. faecalis-cancer cell interaction was observed by the discovering that the expression of gelE in E. faecalis, the gene required for collagenase production, is expressed in response to exposure to CT26 cells. The mechanism by which migration enhancement via E. faecalis occurs appears to be dependent on its ability to activate pro-uPA, a key element of the urokinase-plasminogen system, a pathway that is well - known to be important in cancer cell invasion and migration. Finally, we demonstrated that collagenase producing microbes preferentially colonize human colon cancer specimens.

Solar background noise mitigation using the orbital angular momentum mode in vertical FSO downlink transmissions.

Free-space optical communication (FSO) is used to provide network configuration flexibility. A network-flying platform-based vertical FSO connection can be employed to enhance mobile network coverage and capacity. Solar background noise can be a potential risk that disrupts the seamless connection in the vertical FSO downlink channel. In this paper, we propose signal transmission using an orbital angular momentum (OAM) beam. The OAM demodulation process can filter sunlight out of the optical receiver except for the signal corresponding to the azimuthal state. We experimentally verified that most of the solar background noise could be reduced. To verify the feasibility of the proposed scheme in a vertical FSO channel, we modeled a FSO vertical downlink with an OAM modulation/demodulation process.

Combining stool and stories: exploring antimicrobial resistance among a longitudinal cohort of international health students.

BACKGROUND: Antimicrobial resistance (AMR) is a global public health concern that requires transdisciplinary and bio-social approaches. Despite the continuous calls for a transdisciplinary understanding of this problem, there is still a lack of such studies. While microbiology generates knowledge about the biomedical nature of bacteria, social science explores various social practices related to the acquisition and spread of these bacteria. However, the two fields remain disconnected in both methodological and conceptual levels. Focusing on the acquisition of multidrug resistance genes, encoding extended-spectrum betalactamases (CTX-M) and carbapenemases (NDM-1) among a travelling population of health students, this article proposes a methodology of 'stool and stories' that combines methods of microbiology and sociology, thus proposing a way forward to a collaborative understanding of AMR. METHODS: A longitudinal study with 64 health students travelling to India was conducted in 2017. The study included multiple-choice questionnaires (n = 64); a collection of faecal swabs before travel (T0, n = 45), in the first week in India (T1, n = 44), the second week in India (T2, n = 41); and semi-structured interviews (n = 11). Stool samples were analysed by a targeted metagenomic approach. Data from semi-structured interviews were analysed using the method of thematic analysis. RESULTS: The incidence of ESBL- and carbapenemase resistance genes significantly increased during travel indicating it as a potential risk; for CTX-M from 11% before travel to 78% during travel and for NDM-1 from 2% before travel to 11% during travel. The data from semi-structured interviews showed that participants considered AMR mainly in relation to individual antibiotic use or its presence in a clinical environment but not to travelling. CONCLUSION: The microbiological analysis confirmed previous research showing that international human mobility is a risk factor for AMR acquisition. However, sociological methods demonstrated that travellers understand AMR primarily as a clinical problem and do not connect it to travelling. These findings indicate an important gap in understanding AMR as a bio-social problem raising a question about the potential effectiveness of biologically driven AMR stewardship programs among travellers. Further development of the 'stool and stories' approach is important for a transdisciplinary basis of AMR stewardship.

Influence of gene expression on survival of clear cell renal cell carcinoma.

Approximately 10%-20% of patients with clinically localized clear cell renal cell carcinoma (ccRCC) at time of surgery will subsequently experience metastatic progression. Although considerable progression was seen in the systemic treatment of metastatic ccRCC in last 20 years, once ccRCC spreads beyond the confines of the kidney, 5-year survival is less than 10%. Therefore, significant clinical advances are urgently needed to improve overall survival and patient care to manage the growing number of patients with localized ccRCC. We comprehensively evaluated expression of 388 candidate genes related with survival of ccRCC by using TCGA RNAseq (n = 515), Total Cancer Care (TCC) expression array data (n = 298), and a well characterized Moffitt RCC cohort (n = 248). We initially evaluated all 388 genes for association with overall survival using TCGA and TCC data. Eighty-one genes were selected for further analysis and tested on Moffitt RCC cohort using NanoString expression analysis. Expression of nine genes (AURKA, AURKB, BIRC5, CCNE1, MK167, MMP9, PLOD2, SAA1, and TOP2A) was validated as being associated with poor survival. Survival prognostic models showed that expression of the nine genes and clinical factors predicted the survival in ccRCC patients with AUC value: 0.776, 0.821 and 0.873 for TCGA, TCC and Moffitt data set, respectively. Some of these genes have not been previously implicated in ccRCC survival and thus potentially offer insight into novel therapeutic targets. Future studies are warranted to validate these identified genes, determine their biological mechanisms and evaluate their therapeutic potential in preclinical studies.

Equol, a Blood-Brain Barrier Permeable Gut Microbial Metabolite of Dietary Isoflavone Daidzein, Exhibits Neuroprotective Effects against Neurotoxins Induced Toxicity in Human Neuroblastoma SH-SY5Y Cells and Caenorhabditis elegans.

Emerging data support that plant food based isoflavones have ameliorating effects on a variety of neurodegenerative diseases including Parkinson's disease (PD). Our previous investigation revealed that dietary isoflavones including genistein (GEN), daidzein (DAI), and equol (EQL; a gut microbial metabolite of DAI) showed promising blood-brain barrier permeability and anti-neuroinflammatory activity in murine microglial BV2 cells. However, the neuroprotective effects of EQL against neurotoxins induced toxicity in PD related models remains unclear. Herein, EQL, along with GEN and DAI, were evaluated for their cytoprotective effect in a non-contact co-culture model with LPS-BV2-conditioned media and human neuroblastoma SH-SY5Y cells. In addition, their neuroprotective effects against PD related neurotoxins including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) induced cytotoxicity were evaluated in SH-SY5Y cells. Furthermore, EQL was evaluated for its neuroprotective effects against MPP+ induced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay. DAI (10 µM) and EQL (10 and 20 µM) showed cytoprotective effects by decreasing LPS-BV2-conditioned media induced cytotoxicity in SH-SY5Y cells by 29.2, 32.4 and 27.2%, respectively. EQL (10 and 20 µM) also showed neuroprotective effects by decreasing 6-OHDA and MPP+ induced cytotoxicity in SH-SY5Y cells by 30.6-34.5 and 17.9-18.9%, respectively. Additionally, data from the in vivo assay supported EQL's neuroprotective effect as it increases survival of C. elegans exposed to MPP+ from 72 to 108 h. Our findings support a growing body of evidence of the neuroprotective effects of dietary isoflavones and further studies are warranted to elucidate their mechanisms of action.

Risk factors and renal outcomes of low bone mineral density in patients with non-dialysis chronic kidney disease.

Bone disorder is a common complication of chronic kidney disease (CKD). The clinical usefulness of bone mineral density (BMD) in CKD is not well known. Our study shows that low BMD is associated with physical activity and dietary Na/K intake ratio and can predict poor renal outcome in non-dialysis CKD. PURPOSE: Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD. METHODS: We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by T score: normal (T score ≥ - 1.0), osteopenia (- 1.0 > T score > - 2.5), and osteoporosis (T score ≤ - 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (T score < - 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD). RESULTS: Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12 years; male 61%). Over a median follow-up of 4.3 years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49-0.77)) and spot urine Na/K ratio (1.07 (1.00-1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92-1.41) for osteopenia; 1.43 (1.01-2.04) for osteoporosis, P for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to T score discordance classification. CONCLUSIONS: Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD.

Low hydration status may be associated with insulin resistance and fat distribution: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2010.

We aimed to identify the association of hydration status with insulin resistance (IR) and body fat distribution. A total of 14 344 adults participated in the Korea National Health and Nutrition Examination Survey 2008-2010. We used urine specific gravity (USG) to indicate hydration status, and HOMA-IR (homoeostasis model assessment of IR) and trunk:leg fat ratio (TLR) as primary outcomes. In multivariate logistic regression, the OR per 0·01 increase in USG for high IR was 1·303 (95 % CI 1·185, 1·433; P < 0·001). In multivariate generalised additive model plots, increased USG showed a J-shaped association with logarithmic HOMA-IR, with the lowest Akaike's information criterion score of USG 1·030. Moreover, increased USG was independently associated with increased trunk fat, decreased leg fat and increased TLR. In mediation analysis, the proportion of mediation effects of USG on TLR via IR was 0·193 (95 % CI 0·132, 0·285; P < 0·001), while the proportion of mediation effects of USG on IR via TLR was 0·130 (95 % CI 0·086, 0·188; P < 0·001). Increased USG, a sign of low hydration status and presumably high vasopressin, was associated with IR and poor fat distribution. Direct effect of low hydration status may be more dominant than indirect effect via IR or fat distribution. Further studies are necessary to confirm our findings.

Western Diet Promotes Intestinal Colonization by Collagenolytic Microbes and Promotes Tumor Formation After Colorectal Surgery.

BACKGROUND & AIMS: The Western diet, which is high in fat, is a modifiable risk factor for colorectal recurrence after curative resection. We investigated the mechanisms by which the Western diet promotes tumor recurrence, including changes in the microbiome, in mice that underwent colorectal resection. METHODS: BALB/c male mice were fed either standard chow diet or Western-type diet (characterized by high fat, no fiber, and decreased minerals and vitamins) for 4 weeks; some mice were given antibiotics or ABA-PEG20k-Pi20 (Pi-PEG), which inhibits collagenase production by bacteria, but not bacterial growth, in drinking water. Colorectal resections and anastomoses were then performed. The first day after surgery, mice were given enemas containing a collagenolytic rodent-derived strain of Enterococcus faecalis (strain E2), and on the second day they were given mouse colon carcinoma cells (CT26). Twenty-one days later, distal colons were removed, and colon contents (feces, distal colon, and tumor) were collected. Colon tissues were analyzed by histology for the presence of collagenolytic colonies and by 16S ribosomal RNA sequencing, which determined the anatomic distribution of E faecalis at the site of the anastomosis and within tumors using in situ hybridization. Mouse imaging analyses were used to identify metastases. RESULTS: Colorectal tumors were found in 88% of mice fed the Western diet and given antibiotics, surgery, and E faecalis compared with only 30% of mice fed the standard diet followed by the same procedures. Colon tumor formation correlated with the presence of collagenolytic E faecalis and Proteus mirabilis. Antibiotics eliminated collagenolytic E faecalis and P mirabilis but did not reduce tumor formation. However, antibiotics promoted emergence of Candida parapsilosis, a collagenase-producing microorganism. Administration of a Pi-PEG reduced tumor formation and maintained diversity of the colon microbiome. CONCLUSIONS: We identified a mechanisms by which diet and antibiotic use can promote tumorigenesis by colon cancer cells at the anastomosis after colorectal surgery. Strategies to prevent emergence of these microbe communities or their enzymatic activities might be used to reduce the risk of tumor recurrence in patients undergoing colorectal cancer surgery.

Effects of lysophospholipid supplementation to reduced energy, crude protein, and amino acid diets on growth performance, nutrient digestibility, and blood profiles in broiler chickens.

Two experiments investigated the effects of lysophospholipid (LPL) supplementation on low-energy and low-nitrogenous diets for broilers. A total of 300 one-day-old male chicks (Ross 308) was allotted to 5 treatments in a completely randomized design. Each group consisted of 6 replicates with 10 birds each. Experimental diet I included positive control (PC) having 3,025 (starter), 3,150 (grower), and 3,200 kcal/kg (finisher) of ME; negative control (NC) was 150 kcal/kg of ME lower than PC, and LPL-05, LPL-10, and LPL-15 treatments were NC + 0.05%, 0.10%, and 0.15% of LPL supplementation, respectively. Experimental diet II included positive control (PC) having a formulated amount of crude protein including Lys and Met + Cys that met the Ross 308 standards; negative control (NC) was 4% lower CP and AA than PC; other treatments were supplemented with LPL at 0.05% (LPL-05), 0.10% (LPL-10), and 0.15% (LPL-15) into the NC, respectively. Experiment I showed that growth performance linearly increased as the LPL inclusion increased (P < 0.001). Broilers fed LPL-10 and LPL-15 increased digestibility of DM (P < 0.05), crude protein (P < 0.01), and total amino acids (P < 0.01) compared to NC. Serum glucose (P < 0.01) and high-density lipoprotein (P < 0.05) concentrations were greater in groups fed LPL-10 than those fed PC. Furthermore, leg muscle increased in birds fed LPL-10 compared with NC (P < 0.05). Experiment II observed a linear response to LPL supplementation in the whole period, in terms of body weight gain (P = 0.015) and feed conversion ratio (P = 0.027). Feeding of 0.15% LPL had promising effects on digestibility of crude protein and ether extract compared with NC (P < 0.01 and P < 0.05, respectively). Overall, LPL could be considered as a feed additive to reduced energy (-150 kcal/kg) or nitrogenous diets (-5%) in order to improve growth performance and nutrient digestibility without adverse effects on lymphoid organs and hepatic enzyme of broilers.

Telomere length in peripheral blood leukocytes and risk of renal cell carcinoma.

BACKGROUND: Telomeres are essential for chromosomal stability and may play a key role in carcinogenesis. Telomere length is suggested as a tentative biomarker of risk for renal cell carcinoma (RCC). However, results of previous association studies between telomere length and risk for RCC are inconsistent. METHODS: We evaluated RCC risk in relation to peripheral blood leukocyte telomere length using a hospital-based case-control study of 169 RCC cases and 189 controls. Cases were histologically-confirmed RCC patients who were treated at the Moffitt Cancer Center (Tampa, FL). Controls with no history of cancer underwent a screening exam at the Lifetime Cancer Screening Center at Moffitt Cancer Center to rule out the presence of cancer. Relative telomere length (RTL) was measured by quantitative real-time polymerase chain reaction (PCR) using peripheral blood leukocyte DNA. Logistic regression was used to determine the association between RTL and RCC risk. RESULTS: As expected, increasing age was inversely correlated with RTL (Pearson r=-0.213, P=0.003) among controls but not cases. Average RTL was significantly shorter in cases as compared with controls [mean ± standard deviation (SD): 3.18±1.50 and 4.39±1.99, respectively, P<0.001]. In contrast, average RTL was not significantly different by gender, race, smoking status among controls or by clinical stages among RCC cases. In regression analysis, we observed that shorter RTL is significantly associated with RCC risk [odds ratio (OR) =1.48; 95% confidence interval (CI): 1.27-1.71] after adjustment for covariates. CONCLUSIONS: We found that shorter RTL is associated with an increased risk for RCC. Our findings suggest that telomere length may be involved in the development of RCC.

Translational genomic research: the role of genetic polymorphisms in MBSR program among breast cancer survivors (MBSR[BC]).

Genetic variations of breast cancer survivors (BCS) may contribute to level of residual symptoms, such as depression, stress, fatigue, and cognitive impairment. The objective of this study was to investigate whether particular single-nucleotide polymorphisms (SNPs) moderated symptom improvement resulting from the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR[BC]) program. An overarching goal of personalized medicine is to identify individuals as risk for disease and tailor interventions based on genetic profiles of patients with diseases including cancer. BCS were recruited from Moffitt Cancer Center and University of South Florida's Breast Health Program and were randomized to either the 6-week MBSR(BC) program (n = 92) or Usual Care (n = 93). Measures of symptoms, demographic, and clinical history data were attained at baseline, 6 weeks, and 12 weeks. A total of 10 SNPs from eight genes known to be related to these symptoms were studied using genomic DNA extracted from blood. Our results were examined for effect sizes, consistency, and statistical significance (p < .05). Three SNPs (rs4680 in COMT, rs6314 in HTR2A, and rs429358 in APOE) emerged as having the strongest (though relatively weak) and most consistent effects in moderating the impact of the MBSR program on symptom outcomes. Although effects were generally weak, with only one effect withstanding multiple comparisons correction for statistical significance, this translational behavioral research may help start the identification of genetic profiles that moderate the impact of MBSR(BC). The ultimate goal of this study is the development of personalized treatment programs tailored to the genetic profile of each patient.

Effects of quorum-sensing inhibition on experimental periodontitis induced by mixed infection in mice.

This study aimed to verify, in in vivo settings, whether quorum-sensing inhibition molecules could attenuate alveolar bone loss induced by Porphyromonas gingivalis/Fusobacterium nucleatum co-infection and reduce the bacterial colonization of periodontal tissues. In BALB/c mice, periodontitis was induced through oral inoculation with P. gingivalis and F. nucleatum six times during a 42-d period. Quorum sensing inhibitors (a furanone compound and D-ribose) were administered simultaneously with bacterial infection. Linear and volumetric modifications of interproximal alveolar bone levels were compared between groups using micro-computed tomography. Total bacteria, and P. gingivalis and F. nucleatum DNA in periodontal tissues, were quantified using real-time PCR. Radiographic linear measurements demonstrated a significant reduction of alveolar bone loss, of approximately 40%, in mice treated with quorum sensing inhibitors when compared with the co-infection group. This was confirmed by a significant increase of residual bone volume in the test group. While total bacterial genes in the treatment group significantly decreased by 93% in periodontal tissue samples when quorum sensing inhibitors were administered, no significant differences of P. gingivalis DNA were found. Quorum sensing inhibitors reduced periodontal breakdown and bacterial infection in periodontal tissues after co-infection with P. gingivalis and F. nucleatum.

Levodopa-Reduced Mucuna pruriens Seed Extract Shows Neuroprotective Effects against Parkinson's Disease in Murine Microglia and Human Neuroblastoma Cells, Caenorhabditis elegans, and Drosophila melanogaster.

Mucuna pruriens (Mucuna) has been prescribed in Ayurveda for various brain ailments including 'kampavata' (tremors) or Parkinson's disease (PD). While Mucuna is a well-known natural source of levodopa (L-dopa), published studies suggest that other bioactive compounds may also be responsible for its anti-PD effects. To investigate this hypothesis, an L-dopa reduced (<0.1%) M. pruriens seeds extract (MPE) was prepared and evaluated for its anti-PD effects in cellular (murine BV-2 microglia and human SH-SY5Y neuroblastoma cells), Caenorhabditis elegans, and Drosophila melanogaster models. In BV-2 cells, MPE (12.5⁻50 µg/mL) reduced hydrogen peroxide-induced cytotoxicity (15.7-18.6%), decreased reactive oxygen species production (29.1-61.6%), and lowered lipopolysaccharide (LPS)-induced nitric oxide species release by 8.9⁻60%. MPE (12.5-50 µg/mL) mitigated SH-SY5Y cell apoptosis by 6.9-40.0% in a non-contact co-culture assay with cell-free supernatants from LPS-treated BV-2 cells. MPE (12.5-50 µg/mL) reduced 6-hydroxydopamine (6-OHDA)-induced cell death of SH-SY5Y cells by 11.85⁻38.5%. Furthermore, MPE (12.5-50 µg/mL) increased median (25%) and maximum survival (47.8%) of C. elegans exposed to the dopaminergic neurotoxin, methyl-4-phenylpyridinium. MPE (40 µg/mL) ameliorated dopaminergic neurotoxin (6-OHDA and rotenone) induced precipitation of innate negative geotaxis behavior of D. melanogaster by 35.3 and 32.8%, respectively. Therefore, MPE contains bioactive compounds, beyond L-dopa, which may impart neuroprotective effects against PD.

Risk for Hip Fracture due to Alpha Blocker Treatment in Korean Women: National Health Insurance Database Study.

OBJECTIVE: The aim of this study is to evaluate the risk for hip fracture associated with adverse drug reactions caused by α1-adrenergic (alpha) blockers to treat female voiding dysfunction. METHODS: Information from the Health Insurance Review and Assessment Service database from January 1, 2008 to December 31, 2012 was used. Hip fracture women patients who received a prescription for an alpha blocker due to voiding dysfunction were the cases. A 30-day hazard period after administration of an alpha blocker was set. The 30-day control period was defined as 360 days before administration. The standardized incidence ratio and hazard ratio for the risk of hip bone fracture as related to alpha blocker use were analyzed. RESULTS: The study cohort included 287 383 subjects having a mean age of 65.1 ± 9.7 years in the study cohort. A total of 170 and 79 hip fracture cases were diagnosed in the hazard period and control period, respectively. The incidence of newly diagnosed hip fractures per 100 000 person-years was 763.4 in the hazard period and 348.5 in the control period. The hazard ratio for hip fracture after use of an alpha blocker was 2.19 (95% confidence interval, 1.74-2.77). CONCLUSIONS: Alpha blockers to treat voiding dysfunction may have association with the risk for hip fracture in elderly women.

A Dominant Negative OsKAT2 Mutant Delays Light-Induced Stomatal Opening and Improves Drought Tolerance without Yield Penalty in Rice.

Stomata are the main gateways for water and air transport between leaves and the environment. Inward-rectifying potassium channels regulate photo-induced stomatal opening. Rice contains three inward rectifying shaker-like potassium channel proteins, OsKAT1, OsKAT2, and OsKAT3. Among these, only OsKAT2 is specifically expressed in guard cells. Here, we investigated the functions of OsKAT2 in stomatal regulation using three dominant negative mutant proteins, OsKAT2(T235R), OsKAT2(T285A) and OsKAT2(T285D), which are altered in amino acids in the channel pore and at a phosphorylation site. Yeast complementation and patch clamp assays showed that all three mutant proteins lost channel activity. However, among plants overexpressing these mutant proteins, only plants overexpressing OsKAT2(T235R) showed significantly less water loss than the control. Moreover, overexpression of this mutant protein led to delayed photo-induced stomatal opening and increased drought tolerance. Our results indicate that OsKAT2 is an inward- rectifying shaker-like potassium channel that mainly functions in stomatal opening. Interestingly, overexpression of OsKAT2(T235R) did not cause serious defects in growth or yield in rice, suggesting that OsKAT2 is a potential target for engineering plants with improved drought tolerance without yield penalty.

Neuroprotective effects of a novel poly (ADP-ribose) polymerase-1 inhibitor, JPI-289, in hypoxic rat cortical neurons.

Excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) is known to develop neuronal apoptosis, necrosis and inflammation after ischaemic brain injury. Therefore, PARP-1 inhibition after ischaemic stroke has been attempted in successful animal studies. The purpose of present work was to develop a novel water soluble PARP-1 inhibitor (JPI-289) and explore its neuroprotective effect on ischaemic injury in an in vitro model. The half-life of JPI-289 after intravenous or oral administration in rats was relatively long (1.4-1.5 hours) with 65.6% bioavailability. The inhibitor strongly inhibited PARP-1 activity (IC50 =18.5 nmol/L) and cellular PAR formation (IC50 =10.7 nmol/L) in the nanomolar range. In rat cortical neuronal cells, JPI-289 did not affect cell viability up to 1 mmol/L as assayed by Trypan blue staining (TBS) and lactate dehydrogenase (LDH) assay. Treatment of JPI-289 for 2 hours after 2 hours of oxygen glucose deprived (OGD) rat cortical neuron attenuated PARP activity and restored ATP and NAD+ levels. Apoptosis-associated molecules such as apoptosis inducing factor (AIF), cytochrome C and cleaved caspase-3 were reduced after JPI-289 treatment in the OGD model. The present findings suggest that the novel PARP-1 inhibitor, JPI-289, is a potential neuroprotective agent which could be useful as a treatment for acute ischaemic stroke.

DASH dietary pattern and chronic kidney disease in elderly Korean adults.

BACKGROUND/OBJECTIVES: Dietary patterns are linked to risk and outcomes in chronic kidney disease (CKD). Dietary intake varies by race, region and age. The relationship between a Dietary Approaches to Stop Hypertension (DASH) diet and CKD in elderly Koreans is unclear. SUBJECTS/METHODS: We conducted cross-sectional analyses of 2408 community-dwelling elderly participants from the Korean National Health and Nutrition Examination Survey (2011-2012). DASH dietary patterns for six nutrients (protein, fiber, calcium, potassium, total fat and sodium) were collected by 24 h recall. DASH-US (based on the US recommendations) and DASH-KQ (Korean quartile) scores were generated by summing the scores for the six nutrients. Multivariate logistic regression analysis was used to calculate odds ratio (OR) for the association between a DASH diet and CKD. RESULTS: Mean subject age was 72.4±5.1 years, 13.9% had CKD and 23.8% had diabetes. Protein, fiber, calcium and potassium intake was lower in CKD than non-CKD participants. In multivariate logistic regression analysis adjusted for age, sex, body mass index, comorbid conditions and other factors, a high DASH score was associated with a low odds for CKD based on DASH-US (OR=0.78, 95% confidence interval (CI), 0.65-0.94, P=0.009) and DASH-KQ (OR=0.95, 95% CI, 0.91-0.99, P=0.022). In six nutrients of DASH diet, high fiber intake showed a low odds for CKD in the DASH-KQ model (P for trend=0.010). CONCLUSIONS: Our findings suggest that higher adherence to a DASH diet and higher fiber intake are associated with lower odds of CKD in elderly Koreans. These results should be corroborated through longitudinal studies of the association between a DASH diet and high-fiber diet on the risk of developing CKD.

Chronic kidney disease and high eGFR according to body composition phenotype in adults with normal BMI.

BACKGROUND AND AIMS: Body composition contributes to the risk of chronic kidney disease (CKD) and glomerular hyperfiltration. In adults with normal body mass index (BMI), the relationships of body composition with CKD and high estimated glomerular filtration rate (eGFR) are largely unknown. METHODS AND RESULTS: We analyzed 10,734 adults from the Korean National Health and Nutrition Examination Survey (KNHANES), whose body mass index (BMI) was within the normal range (18.5-24.9 kg/m2). Body composition was categorized into four phenotypes (normal, sarcopenia alone, obesity alone, and sarcopenic obesity) based on appendicular lean mass index (ALMI) and total body fat percentage (TBF%) measured by dual-energy X-ray absorptiometry (DXA). We examined the relationship of CKD and high eGFR (eGFR ≥ 120 ml/min per 1.73 m2) with body composition phenotypes. Sarcopenia alone (14.3%), obesity alone (16.0%), and sarcopenic obesity (10.7%) were prevalent. The association between sarcopenia alone and eGFR was J-shaped, while that between sarcopenic obesity and eGFR was U-shaped. In multivariate logistic regression analysis compared with the normal phenotype, sarcopenic obesity had an elevated odds ratio (OR) for CKD (OR: 1.59, 95% CI: 1.16-2.19). Sarcopenia alone (OR: 1.87; 95% CI: 1.41-2.47) and sarcopenic obesity (OR: 2.37, 95% CI: 1.68-3.36) had elevated OR for high eGFR. CONCLUSION: These findings suggest that decreased muscle mass and coexistence with excess adiposity show associations with CKD and high eGFR even in adults with normal BMI. Body composition measured by DXA could provide information on the relationship of body composition with CKD and high eGFR.