Elevated sperm DNA fragmentation does not predict recurrent implantation failure

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9–105.5] million. Overall median DFI% and HDS% was 12 [7.1–18.9] and 9.6 [6.5–14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98–1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94–1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99–1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99–1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.     

Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury

BackgroundDamage to the renal microvasculature is a hallmark of renal ischemia-reperfusion injury (IRI)–mediated AKI. The miR-17∼92 miRNA cluster (encoding miR-17, -18a, -19a, -20a, -19b-1, and -92a-1) regulates angiogenesis in multiple settings, but no definitive role in renal endothelium during AKI pathogenesis has been established.MethodsAntibodies bound to magnetic beads were utilized to selectively enrich for renal endothelial cells from mice. Endothelial-specific miR-17∼92 knockout (miR-17∼92^endo−/−) mice were generated and given renal IRI. Mice were monitored for the development of AKI using serum chemistries and histology and for renal blood flow using magnetic resonance imaging (MRI) and laser Doppler imaging. Mice were treated with miRNA mimics during renal IRI, and therapeutic efficacies were evaluated.ResultsmiR-17, -18a, -20a, -19b, and pri–miR-17∼92 are dynamically regulated in renal endothelial cells after renal IRI. miR-17∼92^endo−/− exacerbates renal IRI in male and female mice. Specifically, miR-17∼92^endo−/− promotes renal tubular injury, reduces renal blood flow, promotes microvascular rarefaction, increases renal oxidative stress, and promotes macrophage infiltration to injured kidneys. The potent antiangiogenic factor thrombospondin 1 (TSP1) is highly expressed in renal endothelium in miR-17∼92^endo−/− after renal IRI and is a target of miR-18a and miR-19a/b. miR-17∼92 is critical in the angiogenic response after renal IRI, which treatment with miR-18a and miR-19b mimics can mitigate.ConclusionsThese data suggest that endothelial-derived miR-17∼92 stimulates a reparative response in damaged renal vasculature during renal IRI by regulating angiogenic pathways.     

Value of antenatal echocardiography in high risk patients to diagnose congenital cardiac defects in fetus

Results of fetal echocardiography in 1062 high risk pregnant patients are described. It was performed before 28 weeks of gestation in 770 cases. These were 38 abnormal scans (3.6%). A fetal arrhythmia was diagnosed in 14 cases and structural abnormality of the heart in 24. Complete atrioventricular block was commonest (n=12), structural heart disease associated in two of these cases. Other lesions identified were atrioventricular septal defect (n=5), hypoplastic left heart syndrome (n=4), ventricular septal defect (n=4), Ebstein’s anomaly (n=3), coarctation of aorta (n=2) and others (n=9). Postnatal confirmatory echocardiography is available in a total of 993 babies including 36 of 38 abnormal cases. There were eleven neonatal deaths amongst babies with abnormal scans. Errors in interpretation were observed in six instances. An anomaly was missed in five cases; in two of these, the main cardiac malformation was picked up but secondary lesions were missed. In one case, a false positive diagnosis of atrial septal defect was made. These errors did not influence the management of the pregnancy. Fetal echocardiography is a very sensitive (91.6%) and specific (99.9%) tool for antenatal diagnosis of congenital heart disease in high risk pregnancies. The information so obtained helps in guiding the optimal obstetric and neonatal management of these cases.     

Effect of extracts from Phyllanthus watsonii Airy Shaw on cell apoptosis in cultured human breast cancer MCF-7 cells

Species of Phyllanthus have traditionally been used for hundreds of years for treating many ailments including diabetes, anemia, bronchitis and hepatitis. The present study aims to investigate the cytotoxic and apoptotic effects of methanol (PWM), hexane (PWH) and ethyl acetate (PWE) extracts from the leaves of the endemic plant Phyllanthus watsonii Airy Shaw (Phyllanthaceae) on MCF-7 human breast cancer cells. We observed that the PWM, PWH and PWE extracts were cytotoxic and selectively inhibited the growth and proliferation of MCF-7 cells compared to untreated control in a dose dependent manner with an IC₅₀ of 12.7 ± 4.65, 7.9 ± 0.60 and 7.7 ± 0.29 μg/ml, respectively. However, the extracts were not toxic at these concentrations to normal human lung fibroblast MRC-5 cells. Cell death induced by PWM, PWH and PWE extracts were mainly due to apoptosis which was characterized by apoptotic morphological changes and a nuclear DNA fragmentation. Caspase-3 activation following P. watsonii extracts treatment was also evident for apoptotic cell death which was preceded by an S phase cell cycle perturbation. The results suggested that the cytotoxic activity of P. watsonii extracts was related to an early event of cell cycle perturbation and a later event of apoptosis. Hence, P. watsonii displays potential to be further exploited in the discovery and development of new anticancer agents.     

A mindfulness-based strategy for self-management of aggressive behavior in adolescents with autism

Some individuals with autism engage in physical aggression to an extent that interferes with not only their quality of life, but also that of their parents and siblings. Behavioral and psychopharmacological treatments have been the mainstay of treatments for aggression in children and adolescents with autism. We evaluated the effectiveness of a mindfulness-based procedure, Meditation on the Soles of the Feet, in helping three adolescents to manage their physical aggression. This procedure required the adolescents to rapidly shift the focus of their attention from the aggression-triggering event to a neutral place on their body, the soles of their feet. Incidents of aggression across the three adolescents ranged from a mean of 14–20 per week during baseline, 4–6 per week during mindfulness training, including zero rates during the last 4 weeks of intervention. Aggression occurred a rate of about 1 per year during a 3-year follow-up. Our results suggest adolescents with autism can learn, and effectively use, a mindfulness-based procedure to self-manage their physical aggression over several years.     

Inherited bleeding disorders: disorders of platelet adhesion and aggregation

Platelet aggregation at sites of vascular injury is essential for the formation of the primary haemostatic plug. The mechanism of platelet aggregation under conditions of physiological flow is a complex multistep process, which requires the synergistic action of several different platelet receptors. Platelet interaction with collagen at sites of damage to the vascular endothelium involves adhesion, activation, secretion of platelet granular contents and finally aggregation. Other agonists other than collagen, such as fibrinogen, vWF and soluble agonists released from activated platelets (thromboxane A2 (TXA2) and ADP) are involved in platelet aggregation. Platelets express a variety of receptors including GP Ib-IX-V, GP VI, GP Ia-IIa and GP IIb-IIIa. One aspect of this complexity of function is the variety of inherited defects of platelet function. Hereditary disorders of platelet adhesion are Bernard-Soulier syndrome and von Willebrand disease. Glanzmann thrombasthenia is an inherited disorder of platelet aggregation. The application of molecular biology to the study of platelet disorders has identified defects in other collagen receptors, ADP receptors and TXA2 receptors. Defects affecting TXA2 production, the generation of procoagulant activity and secretion from dense bodies and alpha-granules are also encountered. Other rare diseases, Chediak-Higashi, Hermansky-Pudlak and Wiskott-Aldrich syndrome also affect platelet storage granules. In this article, recent advances in the understanding of platelet function and knowledge of inherited disorders that affect platelet adhesion and aggregation is reviewed. As progress advances towards individualisation of therapy the phenotypic bleeding tendency of each patient becomes relevant.     

Cardiac isoform of alpha-2 macroglobulin as a novel diagnostic marker for cardiac diseases.

BACKGROUND: Earlier we showed cardiac isoform of alpha-2 macroglobulin (CA2M) to be an early marker of cardiac hypertrophy. DESIGN: In this study, we tried to explore the possibility of using this protein as a marker for diagnosis of cardiac diseases. METHODS: A total of 593 samples were analyzed for the presence of CA2M using sandwich enzyme-linked immunosorbent assay. RESULTS: Samples include various cardiac diseases (230), non-cardiac ailments (263) and controls (100). CONCLUSION: Levels of CA2M in cardiac diseases were significantly higher than other sample groups but moderately elevated in leprosy. This protein could be considered for diagnosis of cardiac diseases as a serum marker.