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Probiotic potential of Enterococcus spp. is widely investigated around the globe. The biochemically and molecular characterized E. faecium strains isolated from Dahi (continental yogurt) were evaluated to tolerate simulated gastric environment, bile, sodium chloride, temperature, and pH. The safety was assessed by disc diffusion, broth microdilution, antibiotic resistance genes screening, and hemolytic ability. Enterococci survived simulated gastrointestinal conditions and depicted growth at temperature (15 to ≥42°C), pH (≤2.5 to ≥9.5), 0.3% bile salt and 3% NaCl. All strains were sensitive to ampicillin, vancomycin, kanamycin, gentamicin, streptomycin, tetracycline and ciprofloxacin and harbored vanR, vanX, qnrB2, qnrS, tetK, and tetW resistance genes. E. faecium strains inhibited the E. coli (85%) and S. Typhi (50%) whereas the 10% cell-free culture supernatant (CFCS) of E. faecium halted the growth of E. coli while 15% CFCS completely suppressed S. Typhi. The cell-free culture supernatant retained antibacterial nature after pH and proteinase K treatment, however, it lost activity after heat treatment (≥95°C). The genetic screening revealed that all isolates are capable to produce putrescine biogenic amine. Further assessment of strains for lack of infectivity, cytotoxicity in animals, adhesion to Caco-2 cells and characterization of enterocins is essential to conclude the probiotic potential of these strains.

Objectives :To assess and compare Knowledge, Attitude, and Practices of Medical and Nursing Students regarding BLS. Materials and Methods: Design: Cross-sectional study. Setting& Duration :This study was done at Shalamar Institute of Health Sciences, Lahore in a period of 3 months. Inclusion Criteria: Students from all years of MBBS and BS Nursing were taken as subjects .Data Collection and Analysis: Participants satisfying inclusion criteria were requested to fill out a self-structured pre tested questionnaire after informed consent. Data was analyzed using SPSSv.21. Results : There were 330 participants from MBBS and BS Nursing (50 from each class of MBBS and 20 from each class of BS Nursing). The age of participants ranged from 18 to 30 (Figure-I). Only 250 subjects had heard about BLS. Out of 330 participants only 204 had good knowledge about BLS (Table-2) and 126 had poor knowledge of BLS where score of higher than 3 out of 7 was considered as good. Knowledge of Medical and Nursing Students was compared and the p-value came out to be 0.088, which was considered insignificant. Only 34.5% of the participants had learned BLS by training and only 13.3% of the participants (Table-3) had practically done BLS. Most of the people gave no reason for not attending a training session for BLS Conclusion:It was concluded that medical and nursing students had satisfactory knowledge of BLS and more attention was needed towards this important life-saving skill. Keywords: Cardiopulmonary Resuscitation, Medical, Undergraduate, Knowledge, Attitude, Practices , Nursing

Evaluations serve as the backbone of any educational program and can be broadly divided into formative and summative evaluations. Formative evaluations are "just in time" evaluations focused on informing the learning process, whereas summative evaluations compare fellows to a preset standard to determine their readiness for unsupervised practice. In the nephrology fellowship programs, evaluations assess competence in the framework of ACGME Milestones 2.0. A variety of learning venues, evaluators, and tools should be incorporated into the measurement process. It is important to determine which milestones can be best assessed in each education venue to decrease the burden of assessment fatigue. Additionally, programs can diversify the evaluators to include nurses, medical students, peers, and program coordinators in addition to faculty to provide a well-rounded assessment of the fellows and share the assessment burden. Lastly, the evaluation data should be presented to fellows in a format where it can inform goal setting. The evaluation system needs to evolve along with the changes being made in curriculum design. This will help to make fellowship learning effective and efficient.

IntroductionLow serum albumin is associated with high mortality in patients with end-stage renal disease (ESRD) on chronic dialysis. Clinicians are reluctant to offer peritoneal dialysis (PD) as an option for dialysis for patients with low serum albumin due to concerns of loss of albumin with PD, but evidence supporting differences in outcomes is limited. We evaluated mortality based on dialysis modality in patients with very low serum albumin (< 2.5 g/dL).MethodsWe analyzed United States Renal Data System (USRDS) data from 2010 to 2015 to assess mortality by modality adjusted for age, sex, race, employment, number of comorbidities, and year of dialysis initiation.ResultsLow serum albumin (< 2.5 g/dL) was present in 78,625 (19.9%) of 395,656 patients with ESRD on chronic dialysis. Patients with low serum albumin were less likely to use PD as their first modality than those with higher albumin (3.1% vs 10.9%; p < 0.001). Use of PD was associated with lower mortality compared with hemodialysis (HD) (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.81 – 0.95, p < 0.05) in patients with low serum albumin. This difference was more pronounced in patients who had glomerulonephritis (HR = 0.72) or hypertension (HR = 0.81) than in those with end-stage renal disease (ESRD) due to diabetes mellitus or other causes.ConclusionPeritoneal dialysis is less likely to be the first dialysis modality in patients with low serum albumin requiring dialysis. However, PD is associated with lower mortality than HD in patients with low serum albumin on dialysis. We recommend advocating the use of PD in patients with low serum albumin.

Objective Hyperphosphatemia is a common complication in patients with end-stage renal disease on hemodialysis. The mainstay of phosphate management involves a low-phosphate diet and use of phosphate binders, yet these are often insufficient. This study was the first to use behavioral change techniques to encourage the use of phosphate binders and dietary modifications through a series of Phosphate Education and Planning (PEP) talks. Design and Methods A total of 46 hemodialysis patients with hyperphosphatemia were enrolled. All patients were eligible to receive a series of 4 talks, each with defined goals of the long-term management of serum phosphate levels. Qualitative data from the talks were gathered during each intervention, whereas serum phosphate was selected as an outcome measure. Results There was a modest improvement (−0.31 mg/dL) in the serum phosphate levels of the patients who received the entire PEP talk series. Furthermore, the most common self-identified barriers for patients were phosphate binder prescriptions not tailored to their eating routines and lack of resources for suitable dietary changes. Conclusions The PEP talk series model is appropriate to manage persistent hyperphosphatemia despite usual management in outpatient dialysis unit by identifying patient-specific barriers and providing resources that can mitigate them. The strength of this model lies in using a multifaceted approach by applying both pharmacotherapy and dietary changes, along with behavioral change, to achieve lasting improvements in serum phosphate levels in hemodialysis patients with persistently elevated serum phosphate levels.

This chapter discusses the continued high prevalence of renal disease in persons with HIV and the broad pathologic spectrum of renal disease, including medication-induced renal injury. It also allows the learner to understand the importance of screening and monitoring people with HIV for chronic kidney disease. Other topics discussed are the indications for nephrology referral and renal biopsy and potential targets of intervention for HIV-associated renal diseases. Treatment options for people with HIV who have end-stage renal disease, including dialysis and solid organ transplant, are also covered.

Although overall mortality rates in dialysis patients have improved during the last decade or so, infections remain a leading cause of death, second only to cardiovascular disease. In addition, infections account for a major share of hospitalizations in this patient population. Receiving hemodialysis treatments in an outpatient dialysis facility significantly contributes to patients' risks for infection. In dialysis units, patient-to-patient transmission of viral pathogens such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus can occur; proper screening and vaccination of patients can decrease the risk for transmission. Strict adherence to hand hygiene, use of appropriate personal protective equipment, transmission-based precautions, and maintaining aseptic technique while connecting the access to the hemodialysis machine can substantially decrease the likelihood of bacterial infections. With an effective infection control program in place, infection prevention becomes part of the dialysis facility's culture and results in improved patient safety. In this installment of the Core Curriculum series, we highlight best practices that should be followed by health care workers in the dialysis unit and discuss the role of the medical director in promoting initiatives to reduce infection rates.

Background:Overall, a disproportionately small number of end-stage renal disease (ESRD) patients start peritoneal dialysis (PD) in the United States compared to hemodialysis. Little is known about whether gender has an effect on the initial modality of renal replacement therapy utilized by patients; however, prior studies have demonstrated gender disparities in the diagnosis and treatment of various other health conditions, including kidney disease.Methods:Using data from the United States Renal Data System (USRDS), we estimated the proportion of patients utilizing PD as their initial dialysis modality between 2000 and 2014, adjusting estimates to the mean value of all covariates and compared these estimates for women and men.Results:We found that 7.9% of women and 7.5% of men used PD as their initial dialysis modality. The unadjusted odds ratio (OR) of women initiating PD as their initial modality compared to men was 1.04 (95% CI 1.02–1.05, p < 0.001). After adjustment for age, race, ethnicity, cause of ESRD, number of comorbidities, income, employment status, and timing of referral to nephrology, the difference was even more significant, with women being 12% (OR 1.12, CI 1.10–1.14, p < 0.001) more likely to initiate PD than men. However, within different subgroups, older women and women with higher number of comorbidities were less likely to be on PD than their male counterparts.Conclusions:Our results indicate that gender plays a role in the initial dialysis modality used by patients and providers should be cognizant of these gender differences. Further studies are needed to ascertain the cause of this observed difference.

Voids are one of the many material defects present at the microscopic length scale. They are primarily responsible for the formation of cracks and hence contribute to ductile fracture . Circular voids tend to deform into elliptical voids just before their coalescence to form cracks. The principle aim of this study is to investigate the effect of void shape on the micro-mechanism of void growth by using Discrete Dislocation Plasticity simulations. For voided crystals, conventional DDP produces a continuous slip step throughout the material even if a dislocation escapes from a non-convex domain. To overcome this issue, the Extended Finite Element Method (XFEM) is used here to incorporate the displacement discontinuity. Different aspect ratios of elliptical voids are considered under uniaxial and biaxial deformation boundary conditions. The results suggest that voids having the largest surface area tend to have maximum growth rate as compared to void with lower surface area, i.e. “larger is faster ”. Under biaxial loading , a higher magnitude of strain hardening, and void growth rate are observed as compared to uniaxial loading. The results also suggest that the orientation of slip planes as well as voids, affect the overall plastic behavior of the voided-ductile material. Furthermore, circular void tends to induce minimum growth rate but have the maximum strain hardening effect as compared to other void shapes under both loading conditions. The results of this study provide a deeper understanding of ductile fracture with applications in manufacturing industry, aerospace industry and in the design of nano/micro-electromechanical devices i.e. NEMS/MEMS.

Hypoxia-inducible factor-1alpha (HIF-1α) is aberrantly upregulated in tumors and implicated in angiogenesis, metastasis, and drug resistance. Therefore, developing treatments that target HIF-1α may be a viable therapeutic approach. In Traditional Chinese Medicine (TCM), Scutellaria baicalensis (SB) is used for the treatment of cancer but the anti-cancer mechanisms are not known. We examined the effects of SB on HIF-1α expression in ovarian cancer (OC) cell lines grown under normoxic and hypoxic conditions. SB treatment attenuated HIF-1α expression in cancer cell lines. Treatment of cells with cycloheximide (CHX) reduced HIF-1α levels similar to cells treated with SB. Furthermore, SB-induced HIF-1α inhibition was abrogated by the proteasomal inhibitor MG132 and a lysosome inhibitor, chloroquine. Activation of PI3K/AKT and MAPK/ERK seen in OC cells was reduced with SB. Pretreatment of cells with LY294002 (phosphoinositide 3-kinase inhibitor) and PD98059 (mitogen-activated protein kinase inhibitor) reduced HIF-1α expression comparable to SB-treated cells. SB potentiated the anti-growth effects of cisplatin on OC cells by attenuating the expression of HIF-1α, ABCG1, and ABCG2. Taken together, the findings suggest that targeting HIF-1α with SB could be an effective treatment strategy for cancer and SB can improve the sensitivity of cancer cells to cisplatin, which is a major challenge in therapy for ovarian tumors.

Previously, we have demonstrated that progesterone and calcitriol synergistically inhibit growth of endometrial and ovarian cancer by enhancing apoptosis and causing cell cycle arrest. Metastasis is the main reason of mortality in cancer patients. Activation of ADP-Ribosylation Factor 6 (ARF6), Neural Precursor cell expressed Developmentally Downregulated 9 (NEDD9), and Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) have been implicated in promoting tumor growth and metastasis. We examined the effects of progesterone, calcitriol and progesterone-calcitriol combination on metastasis promoting proteins in endometrial cancer. Expression of ARF6, NEDD9, and MT1-MMP was enhanced in advanced-stage endometrial tumors and in cancer cell lines compared to normal tissues and immortalized EM-E6/E7-TERT endometrial epithelial cells. Knockdown of these proteins significantly inhibited the invasiveness of the cancer cells. The expression levels of all three proteins was reduced with progesterone and progesterone-calcitriol combination treatment, whereas calcitriol alone showed no effect on their expression but moderately decreased MT1-MMP activity. Fluorescence microscopy showed membrane expression of MT1-MMP in vehicle and calcitriol-treated endometrial cancer cells. However, progesterone and calcitriol-progesterone combination treatment revealed MT1-MMP in the cytoplasm. Furthermore, progesterone and calcitriol reduced the activity of MT1-MMP, MMP-9, and MMP-2. In addition, invadopodia regulatory proteins were attenuated in both progesterone and progesterone-calcitriol combination treated cells as well as in MT1-MMP knockdown cells. Thus, targeting the aberrant MT1-MMP signaling with progesterone-calcitriol may be a novel approach to impede MT1-MMP mediated cancer dissemination and may have therapeutic benefits for endometrial cancer patients.

Nitric oxide (NO) is implicated in several biological processes, including cancer progression. At low concentrations, it promotes cell survival and tumor progression, and at high concentrations it causes apoptosis and cell death. Until now, the impact of NO donors has not been investigated on human endometrial tumors. Four cancer cell lines were exposed to different concentrations of DETA/NO for 24 to 120 h. The effects of DETA/NO on cell proliferation and invasion were determined utilizing MTS and Boyden chamber assays, respectively. The DETA/NO induced a dose and time-dependent reduction in cell viability by the activation of caspase-3 and cell cycle arrest at the G0/G1 phase that was associated with the attenuated expression of cyclin-D1 and D3. Furthermore, the reduction in the amount of CD133-expressing cancer stem-like cell subpopulation was observed following DETA/NO treatment of cells, which was associated with a decreased expression of stem cell markers and attenuation of cell invasiveness. To understand the mechanisms by which DETA/NO elicits anti-cancer effects, RNA sequencing (RNA-seq) was used to ascertain alterations in the transcriptomes of human endometrial cancer cells. RNA-seq analysis revealed that 14 of the top 21 differentially expressed genes were upregulated and seven were downregulated in endometrial cancer cells with DETA/NO. The genes that were upregulated in all four cell lines with DETA/NO were the tumor suppressors Ras association domain family 1 isoform A (RASSF1) and Cyclin-dependent kinase inhibitor 1A (CDKN1A). The expression patterns of these genes were confirmed by Western blotting. Taken together, the results provide the first evidence in support of the anti-cancer effects of DETA/NO in endometrial cancer.

Increased availability of telehealth, along with patient satisfaction with the modality and financial incentives, makes peritoneal dialysis (PD) an excellent option for qualifying patients living in rural communities. Telemedicine has the potential to radically change the delivery of dialysis care by facilitating the ability of these patients to interact with their PD team via telehealth using a computer with reliable broadband Internet, which many rural clinics and hospitals now possess. Recent legal precedents make this a possibility. Therefore, it is recommended that renal providers take advantage of these favorable conditions to expand the diversity and quality of their practice.

Anti-glomerular basement membrane (GBM) disease is commonly a monophasic illness. We present the case of multiple recurrences of anti-GBM disease with varying serum anti-GBM antibody findings. A 33-year-old female tobacco user presenting with hematuria was diagnosed with anti-GBM disease by renal biopsy. Five years later, she presented with alveolar hemorrhage and positive anti-GBM antibody. She presented a third time with alveolar hemorrhage but undetectable anti-GBM antibody. With each occurrence, symptoms resolved with plasmapheresis, intravenous methylprednisone and oral cyclophosphamide. The relationship between anti-GBM antibody findings and disease presentation is complex. Clinicians should be aware of the possibility of seronegative anti-GBM disease.

The matrix metalloproteinases (MMPs) are implicated in tumor invasion and metastasis. Given their multiple tumor promoting roles, MMPs are promising targets for the treatment of metastatic cancer. Using a siRNA library screen of 140 membrane trafficking genes, we identified 41 genes in HEC-1B and 36 in Ishikawa cancer cells that decreased metalloproteinases activity. The 16 genes common in both cancer cell lines that decreased MMPs activity are involved in cargo sorting, vesicle formation and vesicle recycling. The top two genes clathrin-B and cofilin-1 were chosen for post hoc functional studies. Higher expression of both genes was confirmed in cancer cells and knockdown with respective siRNAs inhibited their invasive potential and matrix metalloproteinases activity. Membrane Type 1- Matrix Metalloproteinase (MT1-MMP) is a master switch proteinase and regulator of invasion and metastasis. A marked decrease in MT1-MMP expression and activity was seen in clathrin-B and cofilin-1 knockdown cancer cells which was associated with a marked decreased expression of invadopodia formation proteins. Our results suggest that the decreased expression of clathrin-B and cofilin-1 decreases the expression of MT1-MMP and results in attenuation of MT1-MMP at the cell surface, thus inhibiting tumor cell invasion and metastasis.

Historically, the placement and maintenance of dialysis access has been an integral part of nephrology training. However, in recent years, a big debate has ensued regarding whether this should be limited to trainees' understanding and counseling the patients regarding indications, alternatives, risks and possible complications of these procedures or should it actually involve more of a hands-on experience for the trainees. Some of the barriers in making these procedures a requirement across the board are the lack of standardization of procedural training across various training programs and the absence of consensus on what achieving competency in these procedures looks like. However, in the era of declining interest in nephrology, giving up "ownership" of nephrology procedures and increasing reliance on other sub specialties might be a deterrent in attracting residents to this field; we have to make a concerted effort to increase the exposure and opportunities for the trainees to perform these procedures. Moreover, we need to emphasize the implementation of a curriculum for nephrology fellows to evaluate access properly in order to decrease the burden of access related complications. Lastly, we need to continue working towards a more structured curriculum for a dedicated interventional nephrology fellowship for trainees who want to focus on procedures for their long-term career goals.

Purpose Several small studies have suggested that the percutaneous method of peritoneal dialysis (PD) catheter insertion is effective and has a lower complication rate than surgical techniques (open, laparoscopic or peritoneoscopic), although no randomized, controlled study has compared these methods. Our objective was to compare percutaneous PD catheter insertion vs surgical placement in terms of 1-year catheter survival, catheter dysfunction, fluid leak and incidence of peritonitis. Methods We searched Medline for English-language literature from 1966 through June 2014, along with national conference proceedings and reference lists of all included publications to identify relevant studies. Inclusion criteria were having a measure of catheter survival at 1 year, catheter dysfunction, peritonitis rate per patient-month or fluid leak as outcomes. Studies were excluded if they were not in English or if they included pediatric patients. Random effects models were used to derive the pooled risk ratios, differences in patency and their variations. Results Thirteen studies with a total of 2,681 subjects met the inclusion criteria. There was no significant difference in 1-year catheter survival in percutaneous vs surgical PD catheter placement (relative risk [RR] = 0.81; 95% confidence interval [CI]: 0.59-1.11, p = 0.19). Catheter dysfunction also did not differ significantly between the groups (pooled odds ratio [OR] = 0.86; 95% CI: 0.57-1.29, p = 0.46). The prevalence of peritoneal fluid leak also was similar for percutaneous and surgical groups (OR = 1.10; 95% CI: 0.58-2.09, p = 0.77). However, there was a significant lower incidence of peritonitis among those with percutaneous placement (incidence rate ratio [IRR] = 0.77; 95% CI: 0.62-0.96, p = 0.02). Significant heterogeneity was detected across studies ( I2 = 78.4%, pConclusions Our results suggest that there is no significant difference in catheter survival between percutaneous and surgical placement of PD catheters. Whether there are significant benefits from percutaneous placement in terms of peritonitis rates requires further robust studies. These findings have significant implications for future design of clinical trials in the placement of PD catheters and the delivery of dialysis-related services.

Background Tenofovir disoproxil fumarate (TDF) may cause acute kidney injury and proximal tubular dysfunction. However, no detailed studies document urinary phosphate wasting as a marker of TDF-induced tubulopathy. Methods Records of HIV-infected patients with presumed TDF toxicity were reviewed. We describe the characteristics and clinical course of 15 patients who had documented elevated (>20%) fractional excretion of phosphate (FEphos). Results Patients were predominantly Caucasian and male (73 and 80%, respectively), with a mean age of 56 years (range 38–76). Of the 15 patients, 11 had a estimated glomerular filtration rate (eGFR) of >90 mL/min/1.732 at time of TDF initiation. The mean duration of TDF therapy prior to diagnosis of TDF toxicity was 64 months. Mean FEphos was 34% (range 20–62). The mean eGFR at TDF initiation was 104 mL/min/1.73 m2 [standard deviation (SD) 17.0] with a gradual decline to 69 mL/min/1.73 m2 (SD 19.0) by the time of TDF discontinuation. Of 10 patients with repeated FEphos after TDF discontinuation, 9 had improvement of their FEphos. Of these individuals, 6 had normalization of their FEphos. Estimated GFR improved in 12 patients after discontinuation of TDF, though importantly, none returned to their baseline eGFR. Conclusions Urinary phosphate wasting is a sensitive marker for TDF-induced proximal tubulopathy and is associated with unrecognized and permanent renal function decline. Tubular dysfunction can develop after years of TDF therapy in those with normal kidney function at the time of drug initiation. This suggests that continuing vigilance be maintained in all those on TDF.

Infection remains the leading complication of peritoneal dialysis (PD). Topical mupirocin and gentamicin are frequently used to prevent infections. Mupirocin ointment has been reported to cause damage to both polyurethane and silicone PD catheters. Gentamicin cream has not been associated with physical damage to catheters.A 64-year-old woman on PD developed relapsing peritonitis with Staphylococcus epidermidis. Because of a drainage problem and white discoloration at the exit site, which is known as " frosting," she underwent catheter exchange. The catheter was found to be fractured within the area of frosting. Four more patients with frosting of the catheter were identified. On further questioning, it was recognized that they were applying excessive amounts of gentamicin cream directly on the catheter surface rather than at the exit site. All patients in the program were educated about the correct method of topical antibiotic application. After the change in practice, no further cases of catheter frosting were identified.Polyurethane catheters can undergo oxidation, mineralization, and environmental stress cracking, leading to physical damage such frosting, ballooning, and fracture. Polyethylene glycol, a component of the mupirocin ointment base, is thought to cause plasticization of polyurethane, reducing its tensile strength. Similar damage has been observed in silicone catheters. Previous reports have not found gentamicin cream to cause that type of damage. We observed that excessive amounts of cream applied directly to the catheter surface can damage it. Damage did not recur once patients had been educated about the proper method of application.

Native biological tissues are viscoelastic materials that undergo time-dependent loading in vivo. It is therefore crucial to ensure that biomedical materials have a suitable viscoelastic response for a given application. In this study, the viscoelastic properties of electrospun poly(vinyl alcohol) are investigated using tensile load relaxation testing. A five-parameter generalised Maxwell constitutive model is found to characterise the experimental response. The effect of polymer concentration and electrospinning voltage on model parameters is investigated in detail. The stiffness coefficients for the relaxation process appear to be dependent on the electrospinning conditions used whereas the time constants remain relatively unchanged. It is also observed that the stiffness parameters are linearly correlated with the equilibrium modulus, indicating that a single underlying material property dictates the relaxation moduli. Lastly, it is found that the viscoelastic model parameters are not predicted by the fibre diameter. These results provide an important understanding in designing electrospun mats with desired time-dependent properties.

Understanding the ratcheting effect of hydrogen and hydride accumulation in response to thermal cycling is important in establishing a failure criterion for zirconium alloy nuclear fuel cladding. We propose a simple discrete dislocation plasticity model to study the evolution of the dislocation content that arises as a micro-hydride repeatedly precipitates and dissolves over a series of thermal cycles. With each progressive thermal cycle, we find a steady growth in the residual dislocation density in the vicinity of the hydride nucleation site; this corresponds to a gradual increase in the hydrogen concentration and, consequently, the hydride population. The simulated ratcheting in the dislocation density is consistent with experimental observations concerning the hysteresis in the terminal solid solubility of hydrogen in zirconium, which can be correlated to the plastic relaxation of hydrides.

Background Although hyperuricemia is common after orthotopic liver transplantation (OLT), its relationship to mortality, progressive kidney disease, or the development of end stage renal disease (ESRD) is not well-described. Methods Data from 304 patients undergoing OLT between 1996 and 2010 were used to assess the association of mean serum uric acid (UA) level in the 3-months post-OLT with mortality, doubling of creatinine, and ESRD incidence. Post-OLT survival to event outcomes according to UA level and eGFR was assessed using the Kaplan Meier method and multivariate Cox proportional hazards models. Results Mean UA level among the 204 patients with an eGFR level ≥60 ml/min/1.73 m2 was 6.4 mg/dl compared to 7.9 mg/dl among the 100 patients with eGFR

Renal disease in persons with HIV has been a major cause of morbidity and mortality since the onset of the epidemic. HIV nephropathy (HIVAN) was the most common form of kidney disease initially seen, but in the post-antiretroviral therapy (ART) era it is much less common. Other renal conditions associated with HIV infection include immune complex disease and classic focal segmental glomerulosclerosis. The pathologic spectrum of renal disease in patients with HIV is extensive. Some conditions, including HIVAN, improve following treatment of the virus with ART. Acute kidney injury is much more common in HIV-infected patients and is associated with a sixfold increase in mortality. Patients with HIV are also much more likely to require renal replacement therapy, including dialysis and renal transplantation. ART may also contribute to renal disease in patients with HIV.

Peritoneal dialysis (PD) is one of the most commonly used forms of renal replacement therapy (RRT) in the world. Along with the rise in end stage renal disease (ESRD) patients, we are seeing an increase in utilization of PD. Most dialysis patients in the United States (US) are on hemodialysis (HD) with PD being less common and home hemodialysis even more so. In this chapter, we will review the use of PD in the US and advantages associated with PD over HD focusing on the lower cost associated with PD therapy. We will also review patient eligibility for PD and the hurdles, which have limited the growth of PD in the US. Lastly, we will assess the factors that lead to transition of PD patients to HD.

Renal disease accounts for significant morbidity and mortality in patients with HIV-1 infection. HIV-associated nephropathy (HIVAN) is an important cause of end stage renal disease in this population. Although multiple genetic, clinical, and laboratory characteristics such as Apolipoproetin-1 genetic polymorphism, high viral load, low CD-4 count, nephrotic range proteinuria, and increased renal echogenicity on ultrasound are predictive of HIVAN, kidney biopsy remains the gold standard to make the definitive diagnosis. Current treatment options for HIVAN include initiation of combined active antiretroviral therapy, blockade of the renin-angiotensin system, and steroids. In patients with progression of HIVAN, renal transplant should be pursued as long as their systemic HIV infection is controlled.

Hypertension is highly prevalent in hemodialysis patients but its management remains a matter of debate. In this review, we discuss the observational studies on the association of blood pressure with outcomes, measurement of blood pressure in hemodialysis patients and present an opinion-based approach to treating hypertension.

// Amber A. Bokhari 1 , Tabari M. Baker 1 , Batsukh Dorjbal 1 , Sana Waheed 1 , Christopher M. Zahn 2 , Chad A. Hamilton 1, 3, 4 , G. Larry Maxwell 3, 4, 5 , Viqar Syed 1, 4, 6 1 Uniformed Services University, Department of Obstetrics and Gynecology, Bethesda, MD 20814, USA 2 American College of Obstetricians and Gynecologists, Washington, DC 20024, USA 3 Women’s Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, Annandale, VA 22003, USA 4 John P. Murtha Cancer Center at Water Reed National Military Medical Center, Bethesda, MD 20889, USA 5 Inova Fairfax Hospital, Department of Obstetrics and Gynecology, Falls Church, VA 22042, USA 6 Uniformed Services University, Department of Molecular and Cell Biology, Bethesda, MD 20814, USA Correspondence to: Viqar Syed, email: viqar.syed@usuhs.edu Keywords: cell proliferation, progesterone, angiogenesis, matrix metalloproteinases, epithelial-mesenchymal-transition Received: April 25, 2016 Accepted: September 02, 2016 Published: September 10, 2016 ABSTRACT Nestin, an intermediate filament protein and a stem cell marker is expressed in several tumors. Until recently, little was known about the expression levels and the role of Nestin in endometrial cancer. Compared to the immortalized endometrial epithelial cell line EM-E6/E7-TERT, endometrial cancer cell lines express high to moderate levels of Nestin. Furthermore, endometrial tumors and tumor cell lines have a cancer stem-like cell subpopulation expressing CD133. Among the cancer lines, AN3CA and KLE cells exhibited both a significantly higher number of CD133+ cells and expressed Nestin at higher levels than Ishikawa cells. Knockdown of Nestin in AN3CA and KLE increased cells in G 0 /G 1 phase of the cell cycle, whereas overexpression in Ishikawa decreased cells in G 0 /G 1 phase and increased cells in S-phase. Nestin knockdown cells showed increased p21, p27, and PNCA levels and decreased expression of cyclin-D1 and D3. In contrast, Nestin overexpression revealed an inverse expression pattern of cell cycle regulatory proteins. Nestin knockdown inhibited cancer cell growth and invasive potential by downregulating TGF-β signaling components, MMP-2, MMP-9, vimentin, SNAIL, SLUG, Twist, N-cadherin, and upregulating the epithelial cell marker E-cadherin whereas the opposite was observed with Nestin overexpressing Ishikawa cells. Nestin knockdown also inhibited, while overexpression promoted invadopodia formation and pFAK expression. Knockdown of Nestin significantly reduced tumor volume in vivo . Finally, progesterone inhibited Nestin expression in endometrial cancer cells. These results suggest that Nestin can be a therapeutic target for cancer treatment.

BackgroundIt remains unclear whether post-transplant outcomes differ according to the pre-transplant dialysis modality (peritoneal dialysis [PD] versus hemodialysis [HD]). We performed a meta-analysis of studies that assessed either post-transplant mortality, graft survival, or delayed graft function (DGF) in both PD and HD patients.MethodsTwo independent authors searched English-language literature from January 1, 1980, through August 31, 2014, national conference proceedings, and reference lists. We used combinations of terms related to dialysis (hemodialysis, peritoneal dialysis, or renal replacement therapy), kidney transplant, and outcomes. Studies were included if they measured any of the 3 post-transplant study outcomes in both pre-transplant HD and PD.ResultsA total of 16 studies were included in the final analysis. Of these, 6 studies reported adjusted hazard ratio for mortality, pooled adjusted risk ratio: 0.89 (95% confidence interval [CI] 0.82 – 0.97) in favor of PD ( p = 0.006). The same 6 studies reported adjusted hazard ratio for graft survival, pooled adjusted risk ratio: 0.97 (95% CI 0.92 – 1.01, p = 0.16). A total of 13 studies reported unadjusted DGF. Pooled odds ratio: 0.5 (95% CI 0.41 – 0.63) in favor of PD ( p < 0.005). Significant heterogeneity observed for all outcomes: I2 = 72.7%, I2 = 59.9%, and I2 = 66.8%, respectively.ConclusionsBased on these results, pre-transplant PD is associated with better post-transplant survival than HD. Pre-transplant PD was also associated with decreased risk for DGF compared with HD, although these results were unadjusted. There was no significant difference in graft survival between pre-transplant HD and PD. These results suggest that PD may be the preferred dialysis modality for patients expected to receive a transplant.

In this study, the effect of temperature on the cyclic deformation behaviour of a confined polycrystalline Nb film is investigated. Micropillars encapsulating a thin niobium interlayer are deformed under cyclic axial compression at different test temperatures. A distinct plastic hysteresis is observed for samples tested at elevated temperatures, whereas negligible plastic hysteresis is observed for samples tested at room temperature. These results are interpreted using planar discrete dislocation plasticity incorporating slip transmission across grain boundaries. The effect of temperature-dependent grain boundary energy and dislocation mobility on dislocation penetration and, consequently, the size of plastic hysteresis is simulated to correlate with the experimental results. It is found that the decrease in grain boundary energy barrier caused by the increase in temperature does not lead to any appreciable change in the cyclic response. However, dislocation mobility significantly affects the size of plastic hysteresis, with high mobilities leading to a larger hysteresis. Therefore, it is postulated that the experimental observations are predominantly caused by an increase in dislocation mobility as the temperature is increased above the critical temperature of body-centred cubic niobium.

Background— The impact of digoxin on outcomes of patients with advanced heart failure (HF) receiving optimal contemporary therapy is not known. Methods and Results— We retrospectively reviewed data of 455 advanced HF patients referred for transplant evaluation (age, 52�12 years; ejection fraction, 18.3�8%); 227 (49.9%) were on digoxin at baseline. Primary outcome was death (n=101), urgent transplantation (n=14), or ventricular assist device implantation (n=4); secondary outcomes included HF and all-cause hospitalizations. Digoxin use was evaluated (1) in the original cohort; (2) in a propensity score–matched subset (n=322); (3) as a time-dependent covariate; and (4) after adjustment for Seattle Heart Failure Score. Patients were on optimal therapy: angiotensin-II modulation, 92.5%; β-blockers, 91.2%; aldosterone antagonists, 45.6%; and devices, 71.0%. After a median of 27 months, 83 of 277 (36.6%) patients treated with digoxin versus 36 of 228 (15.8%) patients without digoxin met primary outcome (hazard ratio [HR], 2.28; 95% CI, 1.51 to 3.43; P P =0.021) and with time-varying digoxin use (HR, 2.05; 95% CI, 1.23 to 3.41; P =0.011). Digoxin was associated with higher risk among patients in sinus rhythm compared with atrial fibrillation. Digoxin was not associated with improvement in either all-cause or HF hospitalization rates. These results were similar across sex and race and when adjusted for Seattle Heart Failure Score and renal function. Conclusion— This study suggests that digoxin therapy may be of no benefit in patients with advanced HF referred for cardiac transplantation who received optimal medical therapy. Treatment with digoxin should be used cautiously in such patients because of risk for adverse outcomes.

Inconclusive findings on abdominal computerized tomography (CT) scans such as "enlarged or prominent pancreas" are commonly reported; however, their clinical significance is not clearly understood. The objective was to evaluate the efficacy of endoscopic ultrasound (EUS) in a cohort of patients with indeterminate findings on CT. We undertook a retrospective, single-center study at a tertiary care university hospital. About 107 consecutive patients (56 men) underwent EUS evaluation for inconclusive CT findings. The main intervention was EUS with fine needle aspiration (FNA) The main outcome measurement was to describe lesions identified by EUS in this cohort of patients. About 22 patients (21%) had pancreatic adenocarcinoma, 14 (13%) had chronic pancreatitis, 28 (26%) had benign lesions, and 35 patients (33%) had a normal EUS exam. Pancreatic cancer was more likely to be found on EUS in patients with significant weight loss (OR 10.1; 95% CI: 3.3-30.60), hyperbilirubinemia (OR 9; 95% CI: 3-26.0), or common bile duct (CBD) dilatation (OR 3.2; 95% CI: 1.25-8.5). The limitations of the study were that we were unable to control the uniformity of CT interpretation because the scans were reviewed by multiple radiologists. There were also limited follow-up data on patients who had benign lesions or normal EUS. In conclusion, EUS is an effective modality for evaluating pancreatic lesions in patients with inconclusive findings on abdominal CT. This assists in the prompt diagnosis and institution of appropriate treatment strategies for a variety of pancreatic diseases including cancer. In the setting of inconclusive CT findings, patients with hyperbilirubinemia, significant weight loss, or CBD dilatation should undergo EUS evaluation as they are at a higher risk of having underlying pancreatic cancer.

Introduction Several studies have demonstrated that renal transplantation in HIV positive patients is both safe and effective. However, none of these studies have specifically examined outcomes in patients with HIV-associated nephropathy (HIVAN). Methods Medical records of all HIV-infected patients who underwent kidney transplantation at Johns Hopkins Hospital between September 2006 and January 2014 were reviewed. Data was collected to examine baseline characteristics and outcomes of transplant recipients with HIVAN defined pathologically as collapsing focal segmental glomerulosclerosis (FSGS) with tubulo-interstitial disease. Results and Discussion During the study period, a total of 16 patients with HIV infection underwent renal transplantation. Of those, 11 patients were identified to have biopsy-proven HIVAN as the primary cause of their end stage renal disease (ESRD) and were included in this study. They were predominantly African American males with a mean age of 47.6 years. Seven (64%) patients developed delayed graft function (DGF), and 6 (54%) patients required post-operative dialysis within one week of transplant. Graft survival rates at 1 and 3 years were 100% and 81%, respectively. Acute rejection rates at 1 and 3 years were 18% and 27%, respectively. During a mean follow up of 3.4 years, one patient died. Conclusions Acute rejection rates in HIVAN patients in this study are higher than reported in the general ESRD population, which is similar to findings from prior studies of patients with HIV infection and ESRD of various causes. The high rejection rates appear to have no impact on short or intermediate term graft survival.

Hypoxia-inducible factor-1alpha (HIF-1α), a transcription factor important for maintaining cellular oxygen homeostasis, is aberrantly upregulated in many tumors and implicated in angiogenesis, metastasis and drug resistance. Therefore, developing treatments that target HIF-1α may be a viable therapeutic approach. For centuries, traditional Chinese medicine has used herbs, such as Scutellaria baicalensis (SB), as a natural remedy for tumors. However, the mechanisms by which SB inhibits tumor growth are not known. We have previously reported that SB inhibits cancer cell proliferation and targets NF-κB in endometrial and ovarian cancers and TGF-β in endometrial cancers. In this study, we examined the effects of SB on HIF-1α protein levels in three ovarian cancer cell lines, SKOV3, OVCA 429, and OVCA 420, grown under normoxic and hypoxic conditions. When treated daily with SB, cancer cells showed a decrease in HIF-1α expression after 48 hours. Investigation into the molecular mechanisms of SB-induced inhibition revealed a significant reduction of HIF-1α accumulation in cells treated with cycloheximide, a protein synthesis inhibitor. Further decrease of HIF-1α accumulation was seen when cycloheximide was combined with SB. Additionally, SB- induced HIF-1α proteasomal degradation was prevented by treatment of cells with proteasomal inhibitor MG132 and chloroquine, lysosome inhibitor, abrogated SB-induced inhibition of HIF-1α. Activation of PI3K/AKT and MAPK/ERK is shown in cancers. SB reduced levels of phospho-AKT and phospho-extracellular signal-related kinase (ERK) in ovarian cancer cells. Furthermore, pretreatment of cells with LY294002 (phosphoinositide 3-kinase inhibitor) and PD98059 (mitogen-activated protein kinase kinase inhibitor) reduced HIF-1α expression comparable to SB-treated cells. Hypoxia-induced cisplatin resistance is a major challenge in therapy of ovarian tumors. SB reduces the proliferation and reverses cisplatin resistance in ovarian cancer cells by attenuating the expression of HIF-1α. Taken together, the findings suggest that targeting HIF-1α with SB could be an effective treatment strategy for ovarian cancer and that SB can improve the sensitivity of cells to cisplatin. Note: This abstract was not presented at the meeting. Citation Format: Imran Hussain, Sana Waheed, Kashif A. Ahmad, John E. Pirog, Viqar Syed. Scutellaria baicalensis targets the hypoxia-inducible factor-1α and attenuates ovarian cancer growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1529. doi:10.1158/1538-7445.AM2017-1529

Nestin, an intermediate filament protein and a stem cell marker is expressed in several cancers. Little is known about the expression level and role of Nestin in endometrial cancer. Compared to immortalized endometrial epithelial cell line EM-E6/E7/TERT, endometrial cancer lines express high to moderate levels of Nestin. Endometrial tumors and tumor cell lines have a cancer stem-like cells population expressing CD133. The AN3CA and KLE cells showed more CD133+ cells and expressed Nestin at higher levels than Ishikawa cells. Knockdown of Nestin in AN3CA and KLE, and overexpression in Ishikawa cells was associated respectively with attenuation and enhancement of CD133+ cells. Knockdown of Nestin increased cells in G0/G1 phase and decreased in S phase, whereas overexpression decreased cells in G0/G1 phase and increased in S phase of cell cycle. Nestin knockdown cells showed increased expression of p21, p27 and PNCA and decreased expression of cyclin-D1 and D3. Nestin overexpression revealed an inverse expression pattern of cell cycle regulatory proteins. Nestin knockdown inhibited cancer cell growth and invasive potential by down regulating TGF-β signaling components, MMP-2, MMP-9, vimentin, SNAIL, SLUG, Twist, N-cadherin, and upregulating E-cadherin. Conversely, Nestin overexpression enhanced cell invasiveness by upregulating TGF-β signaling components, MMP-2, MMP-9, mesenchymal markers and downregulaing epithelial marker, E-cadherin. Nestin knockdown inhibited and overexpression promoted invadopodia formation and pFAK expression. Knockdown of Nestin significantly reduced tumor volume in vivo. Finally, progesterone and a nitric oxide donor inhibited Nestin expression in endometrial cancer cells. These results suggest that Nestin can be a therapeutic target for cancer treatment. Citation Format: Amber A. Bokhari, Batsukh Dorjbal, Tabari M. Baker, Sana Waheed, Christopher M. Zahn, Chad A. Hamilton, George L. Maxwell, Viqar Syed. Nestin suppression attenuates invasive potential of endometrial cancer cells by down regulating TGF-β signaling pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4428.

Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, a respiratory disease that is reemerging worldwide. Mechanisms of selective lymphocyte trafficking to the airways are likely to be critical in the immune response to this pathogen. We compared murine infection by B. pertussis, B. parapertussis, and a pertussis toxin-deleted B. pertussis mutant (BpΔPTX) to test the hypothesis that effector memory T-helper cells (emTh) display an altered pattern of trafficking receptor expression in B. pertussis infection due to a defect in imprinting. Increased cell recruitment to the lungs at 5 days post infection (p.i.) with B. parapertussis, and to a lesser extent with BpΔPTX, coincided with an increased frequency of circulating emTh cells expressing the mucosal-associated trafficking receptors α4β7 and α4β1 while a reduced population of these cells was observed in B. pertussis infection. These cells were highly evident in the blood and lungs in B. pertussis infection only at 25 days p.i. when B. parapertussis and BpΔPTX infections were resolved. Although at 5 days p.i., an equally high percentage of lung dendritic cells (DCs) from all infections expressed maturation markers, this expression persisted only in B. pertussis infection at 25 days p.i. Furthermore, at 5 days p.i with B. pertussis, lung DCs migration to draining lymph nodes may be compromised as evidenced by decreased frequency of CCR7(+) DCs, inhibited CCR7-mediated in vitro migration, and fewer DCs in lung draining lymph nodes. Lastly, a reduced frequency of allogeneic CD4(+) cells expressing α4β1 was detected following co-culture with lung DCs from B. pertussis-infected mice, suggesting a defect in DC imprinting in comparison to the other infection groups. The findings in this study suggest that B. pertussis may interfere with imprinting of lung-associated trafficking receptors on T lymphocytes leading to extended survival in the host and a prolonged course of disease.

Background Fecal incontinence (FI) is a common clinical condition with a negative impact on the quality of life. Commonly performed tests to evaluate FI include anorectal manometry (ARM) and endoanal ultrasonography (EAU). Objective of our study was to compare the results of these 2 tests in a cohort of patients with FI. Methods Retrospective study of 27 patients (20 women) referred to the gastrointestinal motility clinic for FI. EAU and ARM were performed in all patients. Demographic data and information regarding etiology of FI was also recorded. Results Mean age of the patients was 56 years (range 26-87 years). Etiology of FI was obstetric trauma in 4, pelvic surgery in 9, pelvic trauma in 3, pelvic radiation in 1, and idiopathic in 8. Based on the ARM data, 14 of 27 had a weak external sphincter squeeze pressure and 3 had impaired rectal sensation, whereas with the EAU there was thinning of the external anal sphincter in 3 and complete disruption in 1, and abnormalities of the internal anal sphincter (IAS) in 7 of 27 with thinning, and defects. Overall, only 2 of 27 had normal findings by combined ARM and EAU. Conclusions Although the yield of finding major sphincter defects was low, only a small percentage of patients had a normal ARM or EAU. When there are degrees of external anal sphincter thinning or partial or complete disruption of the sphincters, a good correlation with ARM is achieved. EAU and ARM are complimentary investigations for the thorough assessment of the anal sphincter apparatus.

Objectives The aim of this study was to validate the Seattle Heart Failure Model (SHFM) in patients with advanced heart failure (HF). Background The SHFM was developed primarily from clinical trial databases and extrapolated the benefit of interventions from published data. Methods We evaluated the discrimination and calibration of SHFM in 445 advanced HF patients (age 52 ± 12 years, 68.5% male, 52.4% white, ejection fraction 18 ± 8%) referred for cardiac transplantation. The primary end point was death (n = 92), urgent transplantation (n = 14), or left ventricular assist device (LVAD) implantation (n = 3); a secondary analysis was performed on mortality alone. Results Patients were receiving optimal therapy (angiotensin-II modulation 92.8%, beta-blockers 91.5%, aldosterone antagonists 46.3%), and 71.0% had an implantable device (defibrillator 30.4%, biventricular pacemaker 3.4%, combined 37.3%). During a median follow-up of 21 months, 109 patients (24.5%) had an event. Although discrimination was adequate (c-statistic >0.7), the SHFM overall underestimated absolute risk (observed vs. predicted event rate: 11.0% vs. 9.2%, 21.0% vs. 16.6%, and 27.9% vs. 22.8% at 1, 2, and 3 years, respectively). Risk underprediction was more prominent in patients with an implantable device. The SHFM had different calibration properties in white versus black patients, leading to net underestimation of absolute risk in blacks. Race-specific recalibration improved the accuracy of predictions. When analysis was restricted to mortality, the SHFM exhibited better performance. Conclusions In patients with advanced HF, the SHFM offers adequate discrimination, but absolute risk is underestimated, especially in blacks and in patients with devices. This is more prominent when including transplantation and LVAD implantation as an end point.