Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models

Tumor Biology - Protein methylesterase 1 (PME-1) promotes cancerous phenotypes through the demethylation and inactivation of protein phosphatase 2A. We previously demonstrated that PME-1...     

Visual outcome of unilateral traumatic cataract

Objective: To evaluate the visual outcome of a series of patients presenting with unilateral traumatic cataract. Study Design: Observational study. Place and Duration of Study: Ophthalmology Department, Liaquat University Hospital, Hyderabad, from July 2007 to June 2010. Methodology: Analysis included data of 41 patients (31 males and 10 females) with unilateral traumatic cataract. Data regarding demographics, causative agent, clinical course and outcome in terms of best corrected visual acuity (BCVA) was retrieved from the patients' files in hospital record. Data was expressed as frequencies, percentages, mean and standard deviation. Results: There was a male predilection with a male to female ratio of 3.1:1. The age group more frequently affected was 5 - 14 years (58.5%). Commonest causative agent was trauma with wooden stick in 13 eyes (31.7%) followed by thorn in 9 eyes (22%) and stone in 7 eyes (17.1%). Pre-existing posterior capsular defects were observed intraoperatively in 6 eyes. Posterior capsular opacification was evident in 10 eyes (24%). Best corrected visual acuity of 6/18 or more at 6 months was achieved in 29 eyes (70.8%). Duration between injury and cataract surgery did not affect the final visual outcome of traumatic cataract patients. Conclusion: Patients with traumatic cataract if managed appropriately can have best possible visual outcome. Young males are commonly affected. Taking protective measures in sports and work as well as patient education can avoid ocular trauma and traumatic cataract formation.     

Mind the Gap: Bridging the Divide Between Current Binge Drinking Prevention and the Needs of Hispanic Underage Emerging Adults

Prevention Science - In this article, we highlight the urgent public health need for prevention of heavy episodic drinking among underage Hispanic emerging adults in the USA. We outline the current...     

APOE ?2 is associated with white matter hyperintensity volume in CADASIL

Apolipoprotein E (APOE) increases the risk for Alzheimer’s disease (ɛ4 allele) and cerebral amyloid angiopathy (ɛ2 and ɛ4), but its role in small vessel disease (SVD) is debated. Here we studied the effects of APOE on white matter hyperintensity volume (WMHV) in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a nonamyloidogenic angiopathy and inherited early-onset form of pure SVD. Four hundred and eighty-eight subjects were recruited through a multicenter consortium. Compared with APOE ɛ3/ɛ3, WMHV was increased in APOE ɛ2 (P = 0.02) but not APOE ɛ4. The results remained significant when controlled for genome-wide genetic background variation. Our findings suggest a modifying influence of APOE ɛ2 on WMHV caused by pure SVD.     

Klebsiella brain abscess in a neonate

Klebsiella pneumoniae is rarely associated with neonatal cerebral abscess. A case of Klebsiella brain abscess in a neonate is described. Diagnosis of abscess was confirmed by magnetic resonance imaging and ultrasound-guided aspiration.     

Translational bypass of nonsense mutations in zebrafish rep1, pax2.1 and lamb1 highlights a viable therapeutic option for untreatable genetic eye disease

The extensive molecular genetic heterogeneity seen with inherited eye disease is a major barrier to the development of gene-based therapeutics. The underlying molecular pathology in a considerable proportion of these diseases however are nonsense mutations leading to premature termination codons. A therapeutic intervention targeted at this abnormality would therefore potentially be relevant to a wide range of inherited eye diseases. We have taken advantage of the ability of aminoglycoside drugs to suppress such nonsense mutations and partially restore full-length, functional protein in a zebrafish model of choroideraemia (chm(ru848); juvenile chorio-retinal degeneration) and in two models of ocular coloboma (noi(tu29a) and gup(m189); congenital optic fissure closure defects). In vitro cell-based assays showed significant readthrough with two drugs, gentamicin and paromomycin, which was confirmed by western blot and in vitro prenylation assays. The presence of either aminoglycoside during zebrafish development in vivo showed remarkable prevention of mutant ocular phenotypes in each model and a reduction in multisystemic defects leading to a 1.5-1.7-fold increase in survival. We also identified a significant reduction in abnormal cell death shown by TUNEL assay. To test the hypothesis that optic fissure closure was apoptosis-dependent, the anti-apoptotic agents, curcumin and zVAD-fmk, were tested in gup(m189) embryos. Both drugs were found to reduce the size of the coloboma, providing molecular evidence that cell death is required for optic fissure remodelling. These findings draw attention to the value of zebrafish models of eye disease as useful preclinical drug screening tools in studies to identify molecular mechanisms amenable to therapeutic intervention.     

Viscoelastic Characteristics of <Emphasis Type="Italic">In Vitro</Emphasis> Vital and Devitalized Rat Aorta and Human Arterial Prostheses

The arterial wall viscoelasticity plays an essential role in the vascular responsiveness to vasoactive drugs or pathologies. The aim of this investigation was to derive and compare resonance curve (RC), natural frequency (f ₀), dynamic modulus of elasticity (E′), and coefficient of viscosity (β) of (i) vital and devitalized preparations of rat thoracic and abdominal aorta, (ii) human arterial prostheses, and to study the histomorphology of vital and devitalized rat aorta. The method of low frequency forced oscillations was employed. RC of vital preparations showed a hardening type of elasticity whereas in devitalized preparations it was of softening type. E′ increased nonlinearly, f ₀ decreased and β increased linearly with equivalent intraluminal pressure (p _eqi). Distensibility of abdominal aorta was lower than thoracic aorta. Distensibility decreased with increasing p _eqi. E′, f ₀, and β increased significantly after devitalization. It was suggested that postmortem viscoelastic characteristics should not be used directly to specify the vital arteries viscoelasticity. RC of human prostheses showed a softening type of elasticity. Arterial prostheses have low circumferential distensibility with E′-values higher than reported in the literature for human arteries. The method of forced oscillations could be employed for studying the arterial wall biomechanics and viscoelasticity of arterial prostheses. The experiments were carried out in Laboratory Integrative Neuropharmacology, Institute of Neurobiology, BAS, Sofia, Bulgaria and the Department of Anatomy and Histology, Medical University Varna, Varna, Bulgaria.     

Automatic Segmentation of MRI Images in Dynamic Programming Mode

Objective: Purpose of this work was to develop methods contour and volume of areas of interest definition intomographic images of the breast. Methods: The study included images of the breast of 13 patients obtained on an openelectronic resource The Breast-MRI-NACT-Pilot image collection. Statistical processing of the data was carried out, thereliability of the results of calculating the volumes of the breast areas was estimated, a visual evaluation of the obtainednumerical values was provided – a linear graph. Result: A program for automatic determination of breast volume andvolume of pathology has been developed and tested. For segmenting areas of the breast, a threshold segmentation anda managed watershed method programs were written in Matlab package. The developed programs allowed to obtainreliable data when processing MRI images of the breast of 13 patients. Results of using Hurst exponent show that inthe case of a pathology, the exponent is less than 0.4, and for the tissue without pathology the Hurst index is greaterthan 0.4. This method is implemented in dynamic programming mode, which allows to adjust the algorithm for a taskof examining images. Conclusion: The developed methods of definition of contours and calculating volumes allow anautomatic quantitative evaluation of the ratio of the volumes of different identified areas of interest in the postprocessingof MRI images. Also, the results have established that it is possible to use the Hurst exponent as an additional tool foridentifying pathologies in areas of interest.     

Enhancing the Immunogenicity of Vaccinia Virus

The conventional live smallpox vaccine based on the vaccinia virus (VACV) cannot be widely used today because it is highly reactogenic. Therefore, there is a demand for designing VACV variants possessing enhanced immunogenicity, making it possible to reduce the vaccine dose and, therefore, significantly eliminate the pathogenic effect of the VACV on the body. In this study, we analyzed the development of the humoral and T cell-mediated immune responses elicited by immunizing mice with low-dose VACV variants carrying the mutant A34R gene (which increases production of extracellular virions) or the deleted A35R gene (whose protein product inhibits antigen presentation by the major histocompatibility complex class II). The VACV LIVP strain, which is used as a smallpox vaccine in Russia, and its recombinant variants LIVP-A34R*, LIVP-dA35R, and LIVP-A34R*-dA35R, were compared upon intradermal immunization of BALB/c mice at a dose of 10⁴ pfu/animal. The strongest T cell-mediated immunity was detected in mice infected with the LIVP-A34R*-dA35R virus. The parental LIVP strain induced a significantly lower antibody level compared to the strains carrying the modified A34R and A35R genes. Simultaneous modification of the A34R gene and deletion of the A35R gene in VACV LIVP synergistically enhanced the immunogenic properties of the LIVP-A34R*-dA35R virus.     

Female reproductive tract microbiome and early miscarriages

Miscarriage is one of the main causes of reproductive loss, which can lead to a number of physical and psychological complications and other long-term consequences. However, the role of vaginal and uterine microbiome in such complications is poorly understood. To review the published data on the function of the female reproductive tract microbiome in the pathogenesis of early miscarriages. The articles published over the past 20 years and deposited in PubMed, Google Academy, Scopus, Elibrary, ResearchGate, and EBSCO databases were analyzed. The review presents new data on the impact of the vaginal and uterine microbiome on the local immunity, including defense against sexually transmitted infections, and its association with other factors of miscarriages. The studies on the microbiome of non-pregnant women with recurrent miscarriages in the anamnesis, patients undergoing IVF, and pregnant women with miscarriages, as well as new directions in the microbiome research are discussed. The majority of studies have demonstrated that the dominant species of the vaginal and uterine microbiome in patients with early miscarriages are non-Lactobacillus bacteria. As many of these bacteria have not previously been detected by cultural studies and their role in obstetric complications is not well defined, further research on the female reproductive tract microbiome, including the microbiome of the cervix uteri, is needed to develop new approaches for the prognosis and prevention of miscarriages.