Ipilimumab activity in advanced uveal melanoma: A pooled analysis

Background Uveal Melanoma is a rare tumour that displays different clinical behavior and molecular features compared with cutaneous melanoma. It is generally resistant to systemic therapy and there is no current standard effective therapy to treat patients with advanced disease. Patients and methods We searched Medline, PubMed, EMBASE and major oncology conference abstracts from the past 5 years to identify relevant studies evaluating ipilimumab monotherapy in uveal melanoma. Data were extracted on ipilimumab dose, sample size, Objective Response Rate (ORR), Progression Free Survival (PFS), median Overall Survival (mOS), Disease Control Rate (DCR), 1 year Overall Survival (1yrOS) and 2 year Overall Survival (2yrOS). Results Nine studies were included in this study including Phase II clinical trials (n = 2), Expanded Access Programs (EAP) (n = 4) and retrospective studies (n = 3). Cases were a mix of pre-treated and treatment-naïve patients. Reported mOS ranged from 5.2-28 months (median: 9.3 months), and reported 1yrOS ranged between 4.5-65%. Calculated compound ORR was 3.4%, and compound DCR was 36%. Conclusion Ipilimumab has limited clinical activity in advanced uveal melanoma. Further research is needed to identify more effective systemic therapies for management of these patients

CatSper ion channels: Bioinformatics analysis in Homo sapiens

Due to the availability of huge amount of molecular biology data, our main focus was to determine the protein structures, functions and their role in different molecular pathways. The 3-D structure prediction of protein is important in medicine and biotechnology. Molecular docking not only finds the interaction between proteins but also the accurate models of energy of these interacting proteins and helps in further designing of the better drug for that particular protein. The drug targeting is either to inhibit, restore or for the modification of the protein structure. CatSper protein family is calcium ion permeable channels, located in the plasma membrane of sperm tail. It contains a conserved domain of six transmembrane helices in their protein sequence. These four CatSper proteins (1 to 4) assemble and form tetramer, calcium selective channel. It has been found that all members of CatSper protein family (1-4) have a role in hyperactivation in sperm and fertilization processes. As a result of deletion of certain regions (bps) containing these genes along with some other genes, male infertility occurs. We have predicted and analyzed the 3D structures of all members of CatSper protein family in this article. Docking of predicted 3D structures of CatSper protein family, with calcium ion was also performed to verify their interactions.Key words: CatSper, bioinformatics analysis, infertility, cation channel

Echocardiographic parameters and renal outcomes in patients with preserved renal function, and mild- moderate CKD

Abstract Background Echocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality. Methods This retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome. Results 29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality. Conclusions Echocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.https://deepblue.lib.umich.edu/bitstream/2027.42/144773/1/12882_2018_Article_975.pd

Enhanced He-alpha emission from "smoked" Ti targets irradiated with 400nm, 45 fs laser pulses

We present a study of He-like 1s(2)-1s2p line emission from solid and low-density Ti targets under similar or equal to 45 fs laser pulse irradiation with a frequency doubled Ti: Sapphire laser. By varying the beam spot, the intensity on target was varied from 10(15) W/cm(2) to 10(19) W/cm(2). At best focus, low density "smoked" Ti targets yield similar to 20 times more He-alpha than the foil targets when irradiated at an angle of 45 degrees with s-polarized pulses. The duration of He-alpha emission from smoked targets, measured with a fast streak camera, was similar to that from Ti foils

Echocardiographic parameters and renal outcomes in patients with preserved renal function, and mild- moderate CKD

Abstract Background Echocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality. Methods This retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome. Results 29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality. Conclusions Echocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.https://deepblue.lib.umich.edu/bitstream/2027.42/144773/1/12882_2018_Article_975.pd

Illegitimate recombination: An efficient method for random mutagenesis in Mycobacterium avium subsp. hominissuis

Background: The genus Mycobacterium (M.) comprises highly pathogenic bacteria such as M. tuberculosis as well as environmental opportunistic bacteria called non-tuberculous mycobacteria (NTM). While the incidence of tuberculosis is declining in the developed world, infection rates by NTM are increasing. NTM are ubiquitous and have been isolated from soil, natural water sources, tap water, biofilms, aerosols, dust and sawdust. Lung infections as well as lymphadenitis are most often caused by M. avium subsp. hominissuis (MAH), which is considered to be among the clinically most important NTM. Only few virulence genes from M. avium have been defined among other things due to difficulties in generating M. avium mutants. More efforts in developing new methods for mutagenesis of M. avium and identification of virulence-associated genes are therefore needed. Results: We developed a random mutagenesis method based on illegitimate recombination and integration of a Hygromycin-resistance marker. Screening for mutations possibly affecting virulence was performed by monitoring of pH resistance, colony morphology, cytokine induction in infected macrophages and intracellular persistence. Out of 50 randomly chosen Hygromycin-resistant colonies, four revealed to be affected in virulence-related traits. The mutated genes were MAV_4334 (nitroreductase family protein), MAV_5106 (phosphoenolpyruvate carboxykinase), MAV_1778 (GTP-binding protein LepA) and MAV_3128 (lysyl-tRNA synthetase LysS). Conclusions: We established a random mutagenesis method for MAH that can be easily carried out and combined it with a set of phenotypic screening methods for the identification of virulence-associated mutants. By this method, four new MAH genes were identified that may be involved in virulence