Autonomous robotic intracardiac catheter navigation using haptic vision

International audienceWhile all minimally invasive procedures involve navigating from a small incision in the skin to the site of the intervention, it has not been previously demonstrated how this can be done 10 autonomously. To show that autonomous navigation is possible, we investigated it in the hardest place to do it-inside the beating heart. We created a robotic catheter that can navigate through the blood-filled heart using wall-following algorithms inspired by positively thigmotactic animals. The catheter employs haptic vision, a hybrid sense using imaging for both touch-based surface identification and force sensing, to accomplish wall following inside the blood-filled heart. 15 Through in vivo animal experiments, we demonstrate that the performance of an autonomously-controlled robotic catheter rivals that of an experienced clinician. Autonomous navigation is a fundamental capability on which more sophisticated levels of autonomy can be built, e.g., to perform a procedure. Similar to the role of automation in fighter aircraft, such capabilities can free the clinician to focus on the most critical aspects of the procedure while providing precise and 20 repeatable tool motions independent of operator experience and fatigue

Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome.

ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a response signal to cellular challenges, such as excitotoxicity or oxidative stress. This process is catalyzed by a group of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). Because the accumulation of proteins with this modification results in cell death, its negative regulation restores cellular homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome sequencing, we identified recessive inactivating mutations in ADPRHL2 in six families. Affected individuals exhibited a pediatric-onset neurodegenerative disorder with progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. Loss of the Drosophila paralog Parg showed lethality in response to oxidative challenge that was rescued by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition of PARP also rescued the phenotype, suggesting the possibility of postnatal treatment for this genetic condition

An updated meta-analysis of MitraClip versus surgery for mitral regurgitation

Background: Although studies demonstrate its feasibility, there is ongoing debate on the short and long-term outcomes of MitraClip versus surgical repair or mitral valve replacement (MVR). The objective of this meta-analysis is to compare the safety, morbidity, mortality and long-term function following MitraClip compared to MVR.Methods: Articles were searched in PubMed and Cochrane databases for studies comparing outcomes of MitraClip and surgery on December 1, 2019. Eligible prospective, retrospective, randomized and non-randomized studies were reviewed.Results: A total of nine studies (n=1,873, MitraClip =533, MVR =644) were eligible for review. At baseline, MitraClip patients had more comorbidities than MVR patients, including myocardial infarction (P<0.001), chronic obstructive pulmonary disease (P=0.022) and chronic kidney disease (P<0.001). MitraClip was associated with shorter length of stay (-3.86 days; 95% CI, -4.73 to -2.99; P<0.01) with a similar safety profile. Residual moderate-to-severe mitral regurgitation was more frequent in MitraClip at discharge (OR, 2.81; 95% CI, 1.39-5.69; P<0.01) and at five years (OR, 2.46; 95% CI, 1.54-3.94; P<0.01), and there was a higher need for reoperation on the MitraClip group at latest follow-up (OR, 5.28; 95% CI, 3.43-8.11; P<0.01). The overall mortality was comparable between the two groups (HR, 2.06; 95% CI, 0.98-4.29; P=0.06) for a mean follow-up of 4.8 years.Conclusions: Compared to surgery, MitraClip demonstrates a similar safety profile and shorter length of stay in high-risk patients, at the expense of increased residual mitral regurgitation and higher reoperation rate. Despite this, long term mortality appears comparable between the two techniques, suggesting that a patient-tailored approach will lead to optimal results

Establishing recombinant production of pediocin PA-1 in <i>Corynebacterium glutamicum</i>

Bacteriocins are antimicrobial peptides produced by bacteria to inhibit competitors in their natural environments. Some of these peptides have emerged as commercial food preservatives and, due to the rapid increase in antibiotic resistant bacteria, are also discussed as interesting alternatives to antibiotics for therapeutic purposes. Currently, commercial bacteriocins are produced exclusively with natural producer organisms on complex substrates and are sold as semi-purified preparations or crude fermentates. To allow clinical application, efficacy of production and purity of the product need to be improved. This can be achieved by shifting production to recombinant microorganisms. Here, we identify Corynebacterium glutamicum as a suitable production host for the bacteriocin pediocin PA-1. C. glutamicum CR099 shows resistance to high concentrations of pediocin PA-1 and the bacteriocin was not inactivated when spiked into growing cultures of this bacterium. Recombinant C. glutamicum expressing a synthetic pedACD(Cgl) operon releases a compound that has potent antimicrobial activity against Listeria monocytogenes and Listeria innocua and matches size and mass:charge ratio of commercial pediocin PA-1. Fermentations in shake flasks and bioreactors suggest that low levels of dissolved oxygen are favorable for production of pediocin. Under these conditions, however, reduced activity of the TCA cycle resulted in decreased availability of the important pediocin precursor l-asparagine suggesting options for further improvement. Overall, we demonstrate that C. glutamicum is a suitable host for recombinant production of bacteriocins of the pediocin family

Erratum: Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome (The American Journal of Human Genetics (2018) 103(3) (431–439), (S0002929718302374), (10.1016/j.ajhg.2018.07.010))

(The American Journal of Human Genetics 103, 431–439; September 6, 2018) Lisa Weixler has been added to the author list for her experimental and scientific contributions to the biophysical analysis of wild-type and mutant proteins. Her contributions were already mentioned in the acknowledgments. The authors apologize for initially only listing her in the acknowledgments and for the inconvenience. The author list has been corrected online and appears correctly here, and Lisa Weixler's affiliation is indicated as footnote 3: Center for Molecular Medicine Cologne, Cologne, Germany