Optimal reproductive competence of oocytes retrieved through follicular flushing in minimal stimulation IVF

The objective of this study was to assess the reproductive competence of oocytes obtained by follicular flushing in poor responder patients. This prospective comparative study, at the University of Paris XI, Assistance Publique des Hopitaux de Paris, INSERM Unit 782, was performed on 165 infertile IVF embryo transfer candidates. A total of 271 consecutive minimal stimulation IVF cycles were studied. Oocyte retrieval was performed 34 h after human chorionic gonadotrophin administration and oocytes were allocated into two groups according to their retrieval method: oocytes obtained in the first follicular aspiration (FA, n = 127); and oocytes retrieved in the subsequent follicular flushing (FF, n = 102). The principal outcome was to evaluate clinical pregnancy and embryo implantation rates. Thus, patient characteristics, fertilization rate and clinical pregnancy rate per oocyte were comparable in both of groups. In contrast, embryo morphology (41 versus 59%, P < 0.01) and implantation rates (20.4 versus 34.8%, P < 0.04) were better in the FF group. In conclusion, an optimal reproductive competence was observed in oocytes retrieved by follicular flushing in minimal stimulation IVF in poor responder patients.     

Transplanted human cones incorporate into the retina and function in a murine cone degeneration model

Once human photoreceptors die, they do not regenerate, thus, photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation, and synaptic connectivity to the host will be critical in advancing this technology for use in clinical practice. Unlike the unstructured grafts of prior cell-suspension transplantations into end-stage degeneration models, we describe the extensive incorporation of induced pluripotent stem cell (iPSC) retinal organoid–derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extended throughout the graft, even forming a series of adherens junctions between mouse and human cells, reminiscent of an outer limiting membrane. Donor-host interaction appeared to promote polarization as well as the development of morphological features critical for light detection, namely the formation of inner and well-stacked outer segments oriented toward the retinal pigment epithelium. Putative synapse formation and graft function were evident at both structural and electrophysiological levels. Overall, these results show that human photoreceptors interacted readily with a partially degenerated retina. Moreover, incorporation into the host retina appeared to be beneficial to graft maturation, polarization, and function.     

Nox2 underpins microvascular inflammation and vascular contributions to cognitive decline

Chronic microvascular inflammation and oxidative stress are inter-related mechanisms underpinning white matter disease and vascular cognitive impairment (VCI). A proposed mediator is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2), a major source of reactive oxygen species (ROS) in the brain. To assess the role of Nox2 in VCI, we studied a tractable model with white matter pathology and cognitive impairment induced by bilateral carotid artery stenosis (BCAS). Mice with genetic deletion of Nox2 (Nox2 KO) were compared to wild-type (WT) following BCAS. Sustained BCAS over 12 weeks in WT mice induced Nox2 expression, indices of microvascular inflammation and oxidative damage, along with white matter pathology culminating in a marked cognitive impairment, which were all protected by Nox2 genetic deletion. Neurovascular coupling was impaired in WT mice post-BCAS and restored in Nox2 KO mice. Increased vascular expression of chemoattractant mediators, cell-adhesion molecules and endothelial activation factors in WT mice post-BCAS were ameliorated by Nox2 deficiency. The clinical relevance was confirmed by increased vascular Nox2 and indices of microvascular inflammation in human post-mortem subjects with cerebral vascular disease. Our results support Nox2 activity as a critical determinant of VCI, whose targeting may be of therapeutic benefit in cerebral vascular disease.     

Goal choice of alcoholics: A comparison of those who choose total abstinence vs. those who choose responsible,controlled drinking

Examined possible pre-treatment differences between alcoholic veterans who choose total abstinence and those who choose responsible drinking as their drinking goal. The two groups were compared on a variety of behavioral, cognitive, affective, and demographic characteristics. It was found that those who choose responsible drinking had a significantly shorter history of abusive drinking (6.5 years vs. 11.5 years) and more education (12.5 years vs. 10.8 years). In addition, the responsible drinking group showed a stronger belief that their chance for success was 100%.     

Muscle damage and soreness after endurance exercise of the elbow flexors

PURPOSE: This study investigated changes in indirect markers of muscle damage after endurance exercise of the elbow flexors and compared the changes with those after maximal eccentric actions (Max-ECC) of the elbow flexors. METHODS: Eighteen male students rhythmically lifted (1 s) and lowered (1 s) a light dumbbell (1.1-1.8 kg: 9% of MIF) in 60-180 degrees of elbow joint angle for 2 h (2-h Ex). Maximal isometric force (MIF), relaxed (RANG) and flexed elbow joint angles (FANG), upper-arm circumference (CIR), muscle soreness (SOR), B-mode ultrasound (US), and plasma creatine kinase (CK) activity were assessed before and immediately after, and up to 96 h after exercise. RESULTS: All measures were altered significantly (P < 0.05) after 2-h Ex in a similar time course to Max-ECC; however, changes in RANG, FANG, CIR, US, and CK (peak: 356 +/- 121 IU.L-1) were significantly (P < 0.05) smaller compared with those after Max-ECC. SOR developed immediately after 2-h Ex and peaked 24-48 h after exercise. MIF dropped to 44.1% of the preexercise level, which was significantly (P < 0.05) lower than that after Max-ECC (58.1%), immediately postexercise. MIF recovered to 79.8% at 24 h, and 97.8% at 96 h postexercise, which was a significantly (P < 0.05) faster recovery compared with that of Max-ECC (73.1% at 96 h). CONCLUSION: These results showed low-intensity continuous muscle contractions (3600 times) resulted in muscle damage; however, the magnitude of the muscle damage was less severe, and the recovery was faster compared with 12 maximal eccentric muscle actions.