Search

Background: We determined whether oocyte dysmorphisms, especially repetition of specific dysmorphisms from cycle to cycle, had a prognostic impact on intracytoplasmic sperm injection (ICSI) outcome.Methods: ICSI patients (n = 67) were grouped as follows: group 1 >50% phenotypically dysmorphic oocytes per cohort (cytoplasmic and extra-cytoplasmic dysmorphisms) with no repetition of a specific dysmorphism from cycle one to cycle two (36 cycles and 274 oocytes); group 2 >50% dysmorphic oocytes per cohort and repetition of the same dysmorphism from cycle one to cycle two (32 cycles and 313 oocytes); group 3 (control) <30% dysmorphic oocytes (33 cycles and 378 oocytes).Results: In group 2 (repetitive), 47% of oocytes were observed to have organelle clustering versus 20.5% in group 1 and 17.3% in group 3 (P < 0.001). There was no difference between the groups in fertilization rates, cleavage rates or embryo quality. Embryos derived from normal oocytes were transferred in each group (57, 33 and 72% respectively). The clinical pregnancy and implantation rates in group 2 (3.1 and 1.7% respectively) were lower (P < 0.01, P = 0.005) than both group 1 (28 and 15% respectively) and group 3 (45.5 and 26.5% respectively).Conclusions: The low implantation rate in group 2, even though 33% of transferred embryos were derived from morphologically normal oocytes, suggests that repetitive organelle clustering may be associated with an underlying adverse factor affecting the entire follicular cohort. [ABSTRACT FROM AUTHOR]

During DNA virus infections, detection of cytosolic DNA by the cGAS-STING pathway leads to activation of IFN-β. Kaposi's Sarcoma Herpesvirus (KSHV), an oncogenic DNA virus, is the etiological agent of Kaposi's Sarcoma, an endothelial cell (EC)-based tumor. To investigate the role of STING during KSHV infection of primary ECs we identified a primary lymphatic EC sample that is defective for STING activation and we also knocked out STING in blood ECs. Ablation of STING in EC does not increase susceptibility to KSHV latent infection nor does it increase KSHV spread after lytic reactivation indicating STING signaling does not restrict KSHV. In contrast, STING ablation increases Adenovirus spread at low MOI, but STING is dispensable for blocking replication. These experiments reveal that the importance of STING depends on the DNA virus and that STING appears more important for restricting spread to bystander cells than for inhibition of viral replication., (Copyright © 2019. Published by Elsevier Inc.)

Type 2 diabetes (DM) is the most common cause of peripheral neuropathy in the Western world. A comorbidity, hypertension, has been speculated to contribute to initiation or worsening of diabetic peripheral neuropathy. We studied adult rat models using genetic strains with DM (Zucker Diabetic Fat rats)±hypertension (HTN (ZSF-1 rats)) to investigate the relative contributions of DM and HTN and the potential for additive effects of HTN upon existing DM for the development of peripheral neuropathy. Long duration sensorimotor behavioral and electrophysiological testing was complemented by histological and molecular methods. Only DM led to tactile and thermal hyperalgesia and affected motor nerve electrophysiology. Although DM led to marked loss of sensory amplitudes and to sensory conduction slowing, a mild additive effect from HTN contributed after 6months of DM with worsening of slowing of sensory nerve conduction velocities, but without effect upon sensory amplitudes. At the sensory dominant sural nerve, mild (<10%) but greater degrees of myelin thinning were noted with DM and HTN combined, suggesting a mild additive effect. Matrix metalloproteinase (MMP) expression was increased only at the sural nerve in the presence of HTN with co-localization to Schwann cells and myelin. The effects of DM and HTN upon peripheral nerve are dissimilar, with HTN contributing to MMP upregulation at the sites of myelin thinning at sensory nerve fibers, potentially worsening comorbid DM. Together, our results indicate that HTN has a mild additive contribution to diabetic peripheral neuropathy at sensory peripheral nerve fibers manifesting with the loss of myelin thickness., (© 2013.)

Objective: To determine whether [1] survivin is expressed in human oocytes and embryos; [2] embryos grown in vitro secrete survivin protein; and [3] survivin levels are correlated with embryo cleavage rates., Design: Experimental., Setting: University-affiliated IVF clinic., Patient(s): Couples undergoing IVF-ET cycles., Intervention(s): Conventional reverse transcriptase-polymerase chain reaction (PCR), real-time PCR, immunohistochemistry, Western blot on oocytes, embryos and control choriocarcinoma JEG-3 cells, and ELISA analysis of conditioned culture media., Main Outcome Measure(s): Detection of survivin mRNA and protein in oocytes and preimplantation embryos and in JEG-3 cancer cells. Detection of survivin concentrations in embryo culture media., Result(s): Survivin mRNA and protein were expressed during human oocyte maturation, from germinal vesicle to metaphase II stage, and throughout embryo development, from pronuclear stage to blastocyst stage. Survivin was localized predominantly in the cytoplasm of all cells examined and in the oocytes on the chromatin of metaphase chromosomes and midbodies. Western blot analysis of human oocyte and cancer cell extracts detected a full-length (primary) survivin band of 16.5 kDa. Survivin was also detected in conditioned media samples from embryo cultures and showed a positive correlation with embryo cleavage rates., Conclusion(s): Our data have demonstrated for the first time that human oocytes/embryos not only express but also secret survivin, suggesting that survivin may play an important role in human oogenesis and embryogenesis., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Diabetes mellitus types 1 and 2 (DM1 and DM2) and/or hypertension (HTN) can contribute to cognitive decline, cerebral atrophy and white matter abnormalities in humans. Adult rat models of streptozotocin-induced DM1 and genetic strains of DM2 and HTN were used to investigate relative contributions of DM and HTN for alterations in cerebral structure and function as well as insulin receptor biology using cognitive testing, magnetic resonance imaging (MRI), and histological and molecular methods. The effects of DM1 or DM2 were generally similar. DM was associated with earlier onset of cognitive impairment than with HTN alone. DM was independently correlated with brain atrophy, whereas HTN had minimal effects on brain volume. The combination of DM and HTN led to identifiable mild hippocampal neuronal loss while either DM or HTN led to synaptic loss. Only DM led to downregulation of the insulin receptor pathways' activation. In contrast, only HTN was associated with vascular luminal reduction and restricted cerebral perfusion on MRI. The impacts of DM and HTN in the brain differ, while their separate contributions can lead to some additive adverse effects within rodent brain grey matter., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Humans subjected to diabetes mellitus (DM) and/or hypertension (HTN) develop cognitive decline, cerebral atrophy and white matter abnormalities, but the relative effects of DM and HTN upon myelin and axonal integrity is unknown. We studied models of Type 1 (streptozotocin-induced) and Type 2 DM (ZDF) ± HTN (ZSF-1, SHR) in adult rats using magnetic resonance imaging (MRI) and structural and molecular techniques. Type 1 or 2 DM independently led to loss of myelin associated with changes with MRI T2 and magnetization tensor ratios throughout white matter regions. HTN's effect on myelin loss was minimal. Loss of oligodendroglia and myelin proteins was only identified in either Type 1 or Type 2 DM. Activation of the signal transduction pathways initiated by the receptor for advanced glycation end products (AGEs), RAGE, including upregulation of the signal transducer nuclear factor (NF) κB only occurred with DM. Diabetes is a greater contributor to white matter loss than hypertension in the rat brain, while hypertension only plays a mild additive effect upon neurodegeneration in the presence of diabetes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The objective of this prospective randomized double-blind clinical trial was to evaluate whether laser zona pellucida thinning of human embryos improves clinical outcomes in women