Correlations between topological features and physicochemical properties of molecules

The article reviews in brief, thede novo group additivity approach and, at length, the different topological approaches to obtain predictive and internally consistent correlations between various properties and structural features of molecules. The stress has mainly been on the molecular connectivity method. A new rational scheme for nomenclature of connectivity indices of different orders and types is introduced. The concept of the perturbation connectivity parameter developed by us recently has been applied to obtain correlations for molar refraction, boiling point, molar volume, heat of atomisation, heat of combustion, heat of vaporisation, magnetic susceptibility and critical constants of alkanes, alcohols and alkylbenzenes. A comparative study of various approaches reveals that the present perturbation topological approach has an edge over other similar methods

A Patient Registry for the Management of Uterine Fibroids in Canada: Protocol for a Multicenter, Prospective, Noninterventional Study

Background: Uterine fibroids are the most common benign tumor in women. Among those with fibroids, approximately 30% become symptomatic, with abnormal uterine bleeding, pelvic pain, and bulk symptoms. Despite the high prevalence of fibroids, little information is available regarding symptoms, treatment choices, and outcomes for patients. Objective: A Canada-wide patient registry was established to understand the real-world practice. This registry included patient presentation and treatment preferences, health care provider attitudes, and clinical outcomes in the management of symptomatic uterine fibroids. Methods: This study is a prospective, noninterventional, observational patient registry. It will include women diagnosed with uterine fibroids and being managed for symptoms. Participant inclusion criteria were (1) at least 18 years of age, (2) premenopausal with a confirmed diagnosis of uterine fibroids, and associated symptoms, and (3) initiating treatment (drug intervention, procedure intervention, or a combination of both) or watchful waiting. Patients (or legal representative) must understand the nature of the project and provide written informed consent before enrollment. Participant exclusion criteria were (1) they have known or suspected clinically significant pelvic pathology not associated with uterine fibroids, and (2) they are undergoing an emergency hysterectomy at the initial visit. Outcomes will be evaluated in the context of routine clinical practice. Results: Participant recruitment of this registry began in July 2015. This study currently has a total sample of 1500 patients. Conclusions: This registry, a first in Canada, will accumulate evidence on the risks and benefits of watchful waiting, and medical and procedural interventions. It will contribute to enhancing access to treatment options for patients

Immunoprophylaxis against AIDS in macaques with a lentiviral DNA vaccine

AbstractWe earlier reported that immunization of macaques with a reverse transcriptase-deleted SHIVKU2 (ΔrtSHIVKU2) plasmid that contained HIV-1(HXB2) env and SIV gag–nef induced protection against AIDS caused by challenge virus SHIV89.6P with a heterologous env. We further deleted vif and integrase from ΔrtSHIVKU2 and substituted the 3′LTR with SV40 poly A sequences, creating Δ4SHIVKU2 (M) and a parallel construct containing gag–nef of HIV-1SF2, Δ4SHIVKU2 (H). Six macaques received two intramuscular injections of the (M) DNA, and another six received three injections of the (H) DNA. Three of the latter group received two post-challenge boosts with (M) DNA vaccine. Seven virus control macaques were inoculated with SHIV89.6P. All twelve immunized macaques were challenged with SHIV89.6P virus, and CMI responses were measured by ELISPOT assays.Virus control animals all developed progressive infection, whereas vaccinated macaques from both groups controlled virus replication, with plasma viral loads dropping to undetectable levels between weeks 6 and 126 p.i. This DNA vaccine was efficacious even though it encoded Env, Gag, and Nef that were genetically distinct from the proteins in the challenge virus. The DNA vaccine induced broad-based protection without using viral proteins to boost the immunity

Clinical perspectives on the menstrual pictogram for the assessment of heavy menstrual bleeding

Heavy menstrual bleeding (HMB) has an estimated prevalence of 18-32% but is known to be under-reported due to poor recognition and estimation of menstrual blood loss (MBL). HMB can negatively impact quality of life, affecting social interactions, work productivity and sexual life. Abnormal menstrual bleeding may have an underlying structural or systemic cause, such as endometrial and myometrial disorders; however, for some, there is no identified pathological cause. Several methods are available for assessing MBL, including the alkaline hematin (AH) method and the menstrual pictogram (MP). The AH method is considered to be the most accurate way to monitor MBL; however, it is associated with inconvenience and expense, therefore limiting its value outside of research. The MP requires the user to select an icon from a chart that reflects the appearance of a used sanitary product; the icon is associated with a blood volume that can be used to determine MBL. Validation studies have demonstrated that the results of the MP and AH method are well correlated, showing that the MP can measure MBL with sufficient accuracy. Additionally, the MP is more convenient for users, less expensive than the AH method, may be used in regions where the AH method is unavailable and may also be used as part of a digital application. Overall, the MP offers a convenient approach to monitor MBL both in research and clinical practice settings

A balancing act: RNA binding protein HuR/TTP axis in endometriosis patients

Endometriosis, a major reproductive pathology affecting 8-10% of women is characterized by chronic inflammation and immune dysfunction. Human antigen R (HuR) and Tristetraprolin (TTP) are RNA binding proteins that competitively bind to cytokines involved in inflammation including: tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6) among others, and stabilize and destabilize them, respectively. The aim of this study was to examine RNA binding protein (RNABP) HuR/TTP axis in endometriosis patients compared to menstrual stage matched healthy fertile controls in hopes of better understanding their contribution to the pathogenesis of endometriosis. Additionally, using a targeted in vitro siRNA approach, we examined whether knock-down of TTP can play a functional role on other RNABPs that competitively bind to inflammatory targets of TTP in both endometriotic and endometrial epithelial cell lines. Our results suggest that RNABPs TTP and HuR are dysregulated in endometriotic lesions compared to matched eutopic patient samples as well endometrium from healthy controls. Silencing of TTP in endometriotic and endometrial epithelial cells revealed differential response to inflammatory cytokines and other RNABPs. Our results suggest potential involvement of HuR/TTP RNA binding protein axis in regulation of inflammation in endometriosis

IL-17A Contributes to the Pathogenesis of Endometriosis by Triggering Proinflammatory Cytokines and Angiogenic Growth Factors

Endometriosis is a chronic, inflammatory disease characterized by the growth of endometrial tissue in aberrant locations outside the uterus. Neo-angiogenesis or establishment of new blood supply is one of the fundamental requirements of endometriotic lesion survival in the peritoneal cavity. IL-17A is emerging as a potent angiogenic and pro-inflammatory cytokine involved in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. However, sparse information is available in the context of endometriosis. In this study, we demonstrate the potential importance of IL-17A in the pathogenesis and pathophysiology of endometriosis. The data show a differential expression of IL-17A in human ectopic endometriotic lesions and matched eutopic endometrium from women with endometriosis. Importantly, surgical removal of lesions resulted in significantly reduced plasma IL-17A concentrations. Immunohistochemistry revealed localization of IL-17A primarily in the stroma of matched ectopic and eutopic tissue samples. In vitro stimulation of endometrial epithelial carcinoma cells, Ishikawa cells and human umbilical vein endothelial cells with IL-17A revealed significant increase in angiogenic (VEGF, IL-8), pro-inflammatory (IL-6, IL-1β) and chemotactic cytokines (G-CSF, CXCL12, CXCL1, CX3CL1). Furthermore, IL-17A promoted tubulogenesis of HUVECs plated on matrigel in a dose-dependent manner. Thus we provide the first evidence that endometriotic lesions produce IL-17A and that the removal of the lesion via laparoscopic surgery leads to the significant reduction in the systemic levels of IL-17A. Taken together, our data shows a likely important role of IL-17A in promoting angiogenesis and pro-inflammatory environment in the peritoneal cavity for the establishment and maintenance of endometriosis lesions

Thrombospondin-1 signaling through CD47 inhibits self-renewal by regulating c-myc and other stem cell transcription factors

Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells, increases asymmetric division, and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- and thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, whereas CD47 ligation by thrombospondin-1 suppresses c-Myc expression. The inhibitory effects of increasing CD47 levels can be overcome by maintaining c-Myc expression and are absent in cells with dysregulated c-Myc. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors

Correlation between Topological Features & Critical Constants of Alkanes, Aliphatic Monoalcohols & Alkylbenzenes

545-54

Correlation of second virial coefficients of alkanes. Alkylbenzenes and alkanols with their topological features

The second viral coefficients of 11 alkanes at 298.15K, 8 alkanols at 393.20K and 5 alkylbenzenes at 393.10K hve been correlated with their topological features quantified in terms of valence connectivity indices. For a given series the correlations are internally consistent and can predict virial coefficients within the experimental limits