Intrapartum translabial ultrasound with pushing used to predict the difficulty in vacuum-assisted delivery of fetuses in non-occiput posterior position

Objective: Our aim is to evaluate the capacity of intrapartum translabial ultrasound (ITU) with pushing in the prediction of difficulty of fetal extraction in vacuum assisted deliveries. Prospective, observational study performed (2/2015–8/2015) on 75 nulliparous women, ≥37 weeks with singleton pregnancies at full dilatation who had ITU-with-pushing performed, previous to vacuum-placement for fetal extraction. Working on the translabial sagittal-plane, we assessed: Angle-Progression (AoP), Progression-Distance (PD) and Head-Direction (HD); in the axial plane we evaluated: Midline-Angle (MLA) and Head-Perineum-Distance (HPD). Vacuum extractions were classified as easy-difficulty (ED) (≤3 vacuum-pulls), difficult-unsuccessful (DD) (>3 vacuum-pulls). We did not assess occipito-posterior-presentations.

Results: Seventy nulliparous were studied (44-ED,26-DD). We observed no differences in obstetric, neonatal or intrapartum characteristics between the two study groups, with the following exceptions: newborn weight (3272?±?438?g versus 3540?±?372?g; p?=?0.011) and number of vacuum-pulls (1.4-ED-vs-4.4-DD; p?<?0.0005). AoP-pushing was 143.9°?±?14.6° in ED and 115.1°±?12.9° in DD (p?<?0.0005); Head-Up was 79.5% versus 38.4% (p?<?0.0005); PD-Pushing was 42.7?±?11.3?mm versus 30.4?±?9.8?mm (p?<?0.0005); MLA-Pushing was 27.6°±?26.6° versus 57.5°±26.5°(p=0.025); HPD-Pushing was 40.8?±?10.0?mm versus 47.4?±?10.9?mm (p?=?0.039).

Conclusion: We identified that the presence of an AoP-Pushing?>?128° predicts an Easy-Vacuum-Delivery (≤3 Vacuum-Pulls) in >85% of cases (Sen 80%–FPR 9.3%).     

Alterations in Bacterial Metabolism Contribute to the Lifespan Extension Exerted by Guarana in Caenorhabditis elegans

Guarana (Paullinia cupana) is a widely consumed nutraceutical with various health benefits supported by scientific evidence. However, its indirect health impacts through the gut microbiota have not been studied. Caenorhabditis elegans is a useful model to study both the direct and indirect effects of nutraceuticals, as the intimate association of the worm with the metabolites produced by Escherichia coli is a prototypic simplified model of our gut microbiota. We prepared an ethanoic extract of guarana seeds and assessed its antioxidant capacity in vitro, with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and in vivo, utilizing C. elegans. Additionally, we studied the impact of this extract on C. elegans lifespan, utilizing both viable and non-viable E. coli, and assessed the impact of guarana on E. coli folate production. The extract showed high antioxidant capacity, and it extended worm lifespan. However, the antioxidant and life-extending effects did not correlate in terms of the extract concentration. The extract-induced life extension was also less significant when utilizing dead E. coli, which may indicate that the effects of guarana on the worms work partly through modifications on E. coli metabolism. Following this observation, guarana was found to decrease E. coli folate production, revealing one possible route for its beneficial effects.     

Efficacy and safety of daclatasvir‐based antiviral therapy in hepatitis C virus recurrence after liver transplantation. Role of cirrhosis and genotype 3. A multicenter cohort study

Direct‐acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC‐based regimens in a large real‐world cohort. A total of 331 patients received DCV‐based therapy. Duration of therapy and ribavirin use were at the investigator's discretion. The primary end point was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Intention‐to‐treat (ITT) and per‐protocol SVR were 93.05% and 96.9%. ITT‐SVR was lower in cirrhosis (n = 163) (96.4% vs. 89.6% P = 0.017); the SVR in genotype 3 (n = 91) was similar, even in advanced fibrosis (96.7% vs. 88%, P = 0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died during treatment. A total of 22 patients (6.6%) died. Albumin (HR = 0.376; 95% CI 0.155–0.910) and baseline MELD (HR = 1.137; 95% CI: 1.061–1.218) were predictors of death. DCV‐based DAA treatment is efficacious and safe in patients with HCV infection after LT. Baseline MELD score and serum albumin are predictors of survival irrespective of viral response.     

Mitochondrial Networking Protects ��-Cells From Nutrient-Induced Apoptosis

OBJECTIVE

Previous studies have reported that β-cell mitochondria exist as discrete organelles that exhibit heterogeneous bioenergetic capacity. To date, networking activity, and its role in mediating β-cell mitochondrial morphology and function, remains unclear. In this article, we investigate β-cell mitochondrial fusion and fission in detail and report alterations in response to various combinations of nutrients.

RESEARCH DESIGN AND METHODS

Using matrix-targeted photoactivatable green fluorescent protein, mitochondria were tagged and tracked in β-cells within intact islets, as isolated cells and as cell lines, revealing frequent fusion and fission events. Manipulations of key mitochondrial dynamics proteins OPA1, DRP1, and Fis1 were tested for their role in β-cell mitochondrial morphology. The combined effects of free fatty acid and glucose on β-cell survival, function, and mitochondrial morphology were explored with relation to alterations in fusion and fission capacity.

RESULTS

β-Cell mitochondria are constantly involved in fusion and fission activity that underlies the overall morphology of the organelle. We find that networking activity among mitochondria is capable of distributing a localized green fluorescent protein signal throughout an isolated β-cell, a β-cell within an islet, and an INS1 cell. Under noxious conditions, we find that β-cell mitochondria become fragmented and lose their ability to undergo fusion. Interestingly, manipulations that shift the dynamic balance to favor fusion are able to prevent mitochondrial fragmentation, maintain mitochondrial dynamics, and prevent apoptosis.

CONCLUSIONS

These data suggest that alterations in mitochondrial fusion and fission play a critical role in nutrient-induced β-cell apoptosis and may be involved in the pathophysiology of type 2 diabetes.Mitochondria mediate β-cell responses to extracellular glucose by generating ATP and initiating a cascade of events culminating in the release of insulin. It is not surprising that β-cell mitochondria have become an important target for investigations into the etiology of type 2 diabetes. Mitochondria are highly dynamic organelles whose morphology is regulated by cycles of fusion and fission, collectively termed mitochondrial dynamics (1,2). Networks are formed when mitochondria undergo fusion events that cause the compartments of participating mitochondria to become continuous. As a result, the constituents of each network share solutes, metabolites, and proteins (3–5) as well as a transmembrane electrochemical gradient (1,6). The disruption of such networks has been shown to have a profound effect on the progression of cells to apoptosis, particularly in cases where reactive oxygen species (ROS) are involved (7). As such, mitochondrial networking is thought to be a potential defense mechanism allowing for the buffering of mitochondrial ROS and calcium overload (8,9).Chronically elevated levels of glucose and fatty acid are thought to contribute to the progression of type 2 diabetes by adversely affecting β-cells and thereby causing a deterioration in insulin secretion (10). In vivo, a reduction in insulin gene expression due to reduced Pdx-1 binding has been observed in rats perifused with glucose and intralipids (11,12). In addition, exposure to high levels of glucose and/or free fatty acid has been shown to affect β-cell viability by inducing mitochondrial apoptosis and has been linked to ROS-induced mitochondrial calcium overload and damage (13). Recent studies indicate that nutrient-induced ROS increases subcellular mitochondrial membrane potential (ΔΨmt) heterogeneity and fragmentation of the mitochondrial architecture (14,15). These findings suggest that mitochondrial fragmentation-defragmentation might play a role in the effects of noxious stimuli. Although the functional significance of these changes has not been studied in β-cells, studies of mitochondrial morphology in other cells have demonstrated that the ability of mitochondria to form networks influences both ROS and calcium handling (7–9).Previous studies have reported that β-cell mitochondria form less elaborate network structures, compared with COS cells for example, and raise doubts on the existence of mitochondrial networking in these cells. Until now, technologies for examining and quantifying the ability of mitochondria to undergo fusion and fission were unavailable.In this work, we show that the densely packed appearance of mitochondria in the β-cell represents the existence of multiple juxtaposed units that do not share continuous matrix lumen but do go through frequent fusion and fission events. We further demonstrate that mitochondrial dynamics are disrupted by exposure to the combination of high fat and glucose, gradually leading to the arrest of fusion activity and complete fragmentation of the mitochondrial architecture. Inhibiting mitochondrial fission preserved mitochondrial morphology and dynamics and prevented β-cell apoptosis.     

AT-1 receptor antagonism modifies the mediation of endothelin-1, thromboxane A2, and catecholamines in the renal constrictor response to angiotensin II

OBJECTIVE: The present study investigated the consequences of partial AT(1) receptor blockade on the participation of catecholamines, thromboxane A(2) (TXA(2)), and endothelin-1 (ET-1) in the renal vasoconstriction induced by angiotensin II (Ang II). METHODS: For this purpose, the increase in renal perfusion pressure (RPP) produced by Ang II was studied in isolated kidneys from untreated or irbesartan-treated Wistar Kyoto and spontaneously hypertensive rats (SHR), in absence or presence of the alfa-1 receptor antagonist, prazosin, the TXA(2) receptor antagonist, ifetroban, or the ET(A)/ET(B) receptor antagonist, PD145065. RESULTS: Systolic arterial pressure (SAP) was higher (P < 0.05) in SHR than in WKY. Increases in RPP produced by Ang II were comparable in kidneys from both untreated groups. Treatment with irbesartan reduced SAP and RPP in both strains in a comparable extent. Presence of prazosin, ifetroban, or PD145065 in perfusion media reduced (P < 0.05) Ang II maximal response in all groups. Maximal inhibition of Ang II-induced vasoconstriction produced by the 3 antagonists was comparable in untreated WKY, but that of ifetroban and PD145065 was lower (P < 0.05) than that of prazosin in untreated SHR. Maximal inhibition of Ang II-induced vasoconstriction produced by the 3 antagonists was comparable in WKY treated with irbesartan, and not different to that observed in untreated WKY. Maximal inhibitory effect of the 3 antagonists was higher (P < 0.05) in treated than in untreated SHR. CONCLUSION: The study further supports the importance of catecholamines, TXA(2), and ET-1 as mediators of the renal vasoconstriction induced by Ang II in both normotensive and hypertensive rats. Hypertensive conditions appeared to reduce the participation of TXA(2) and ET-1 in Ang II-induced vasoconstriction when compared with normotensive conditions. Chronic partial blockade of AT(1) receptors did not affect the participation of catecholamines, TXA(2), and ET-1 in normotensive rats, but increased the participation of the 3 mediators in SHR. This suggests that when AT(1) receptors are partially blocked, other vasoconstrictor factors could exert part of the renal vasoconstrictor effects of Ang II.     

Use of speckle tracking in the evaluation of late subclinical myocardial damage in survivors of childhood acute leukaemia

Heart disease is the leading cause of non-cancer death in childhood cancer survivors. to determine the prevalence of subclinical cardiac dysfunction using speckle tracking and compare its results with those obtained by classical methods of assessing left ventricular function and its relationship with different factors to identify the population at higher risk. Echocardiographic assessment of left ventricular function included ejection fraction, tissue Doppler, longitudinal/circumferential strains and biochemical parameters (troponin-T and Pro-BNP) in a cohort of 57 survivors of childhood acute leukaemia with at least 10 years since diagnosis. Ventricular dysfunction was found in 5.2% of patients in M-mode (ejection fraction—EF?<?53% with a reduction in the EF?≥?10%) and in 7% of patients with Simpson’s method, compared with 21.05 and 8.8% with suboptimal global longitudinal strain (GLS) and global circumferential strain, respectively. The GLS alteration was significantly correlated with lower values of left ventricular systolic function and was associated with high tumour risk (odds ratio [OR] 13.8), cumulative doses of anthracyclines?≥?250 mg/m² (OR 7.6) and radiotherapy (OR 7.19). Biomarkers were not useful for the diagnosis of subclinical cardiomyopathy. Good reproducibility was obtained, with an intraobserver correlation of 93.6% and an interobserver correlation of 89.2% in the GLS. The alteration of the GLS was more prevalent than the alteration in the EF and was associated with the treatment received and high tumour risk. strain imaging seems to be a powerful tool to identify an increased number of survivor with an early myocardial injury.