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The edge-to-edge mitral valve repair technique, invented by Alfieri and colleagues, introduced valve repair as a treatment option for patients with complex diseases where standard annuloplasty and related repair techniques are insufficient, due to annular calcification and patient frailty. We retrospectively evaluated the results of a transaortic edge-to-edge mitral valve repair (Alfieri stitch) in high-risk patients who were undergoing aortic valve replacement. From February, 2012 to December, 2017, 43 patients underwent transaortic edge-to-edge mitral valve repair with concomitant aortic valve replacement at a single institution. Preoperative and postoperative echocardiograms were compared. Home telephone follow up was conducted and postoperative morbidity was examined, including the need for reoperation, stroke and cardiac arrhythmia. 30-day and long-term survival rates were also determined. Mitral regurgitation (MR) was graded semi-quantitatively as 0 (trace and/or none), mild (1), moderate (2) or moderate to severe (3-4). The patients were 74 ± 7.8 years old. 65% of the patients were male. Mean cardiopulmonary bypass time was 115 ± 37 minutes and mean cross-clamp time was 71 ± 23 minutes. There was a significant improvement in preoperative vs postoperative median MR grade (2 (IQR 2-3) vs 0 (IQR 0-1); P = 0.05). Follow-up transthoracic echocardiograms in 29 patients obtained at a median of 9 months' (range 3 - 19 months') and in 16 patients at a median of 34 months' postoperatively (range 21 - 53 months') showed mild (1 (IQR 1-2)) grade of mitral regurgitation. 30-day survival was 98%. Long term survival at 12 and 24 months' were 88% and 81% respectively. Mitral valve reoperation was conducted in 1 patient (2%), who was suffering of endocarditis. Stroke occurred in 2 patients (7%). Cardiac arrhythmia was observed in 15 patients (35%). 8 patients (19%) suffered from atrial fibrillation and 7 patients (16%) displayed atrioventricular blockage. 10 patients (23%) could be treated conservatively and 5 patients (12%) needed implantation of a pacemaker. Transaortic edge-to-edge mitral valve repair can be safely performed during aortic valve replacement in high-risk patients and improves even long-term MR grade. Postoperative cardiac arrhythmia occurs frequently. 66% of them could be treated successfully by conservative procedures.

The adsorption of DNA at mineral-water interfaces is well-established to increase its persistence in soils and sediments; however, adsorbed RNA in similar environments degrades rapidly, in some cases outpacing solution-phase degradation occurring over hours to days. Herein, we elucidate a novel abiotic mechanism by which RNA, but not DNA, degrades upon adsorption to surfaces of iron (oxyhydr)oxides such as goethite (α-FeOOH) that are abundant in soils and sediments. Upon adsorption to goethite, both single-stranded and double-stranded RNA hydrolyzed on the timescale of hours under environmentally relevant physicochemical conditions. The reaction products were consistent with iron present in goethite acting as a Lewis acid to accelerate non-selective hydrolysis of phosphodiester bonds comprising the RNA backbone. In contrast to well-established acid- or base-catalyzed RNA hydrolysis in solution, mineral-catalyzed hydrolysis was fastest at circumneutral pH, which allowed for both sufficient RNA adsorption and hydroxide concentration. We further confirmed that contact of the RNA with the mineral surface is necessary for hydrolysis to occur by demonstrating RNA degradation was inhibited by compact RNA conformation at elevated ionic strength and competitive adsorption with orthophosphate and organic matter. In addition to goethite, we observed RNA hydrolysis was also catalyzed by hematite (α-Fe2O3), but not by aluminum-containing minerals (e.g., montmorillonite). Given the extensive adsorption of nucleic acids to environmental surfaces, we anticipate previously overlooked mineral-catalyzed hydrolysis of RNA may be prevalent particularly in iron-rich soils and sediments, which must be considered across biogeochemical applications of nucleic acid analysis in environmental systems.

Amines are frequently included in formulations of the herbicides glyphosate, 2,4-D, and dicamba to increase herbicide solubility and reduce herbicide volatilization by producing herbicide-amine salts. Amines, which typically have higher vapor pressures than the corresponding herbicides, could potentially volatilize from these salts and enter the atmosphere, where they may impact atmospheric chemistry, human health, and climate. Amine volatilization from herbicide-amine salts may additionally contribute to volatilization of dicamba and 2,4-D. In this study, we established that amines applied in herbicide-amine salt formulations undergo extensive volatilization. Both dimethylamine and isopropylamine volatilized when aqueous salt solutions were dried to a residue at ∼20 °C, while lower-vapor pressure amines like diglycolamine and

Literature on the air travel activities of patients supported by permanent mechanical assist devices is rare. To the best of our knowledge, no air travel guidelines or fitness prerequisites exist on whether and when ventricular assist device (VAD) patients are allowed to travel by plane after device implantation. In this study, we evaluated the topic of air travel after VAD implantation. This working group aimed to produce a report on air travel passengers supported by VADs, regarding their fitness to fly. Fifty left ventricular assist device (LVAD) patients were surveyed in a worldwide multicenter study. The single survey was performed with a multimethod design, including interviews conducted face‐to‐face, online, and on phone. Out of 50 patients, 97% described their traveling by aircraft as perfect and uneventful during the flight. Eighty‐five percent of the study participants consulted their medical practitioner before the flight. No patient reported the occurrence of a severe condition associated with flying. LVAD alarms, especially low flow alarms, did not occur in any of the devices. Thirty‐five percent of the surveyed patients, however, stated a major problem pertaining to the security check procedures at the airport. The results of this study suggest that commercial air travel is safe for stable patients on permanent VAD support and traveling can be resumed securely after VAD implantation. Conscientious preparation by packing necessary devices, fluids, medications, and careful preparation for the airport security check is recommended.

The stability of RNA in aqueous systems is critical for multiple environmental applications including evaluating the environmental fate of RNA interference pesticides and interpreting viral genetic marker abundance for wastewater-based epidemiology. In addition to biological processes, abiotic reactions may also contribute to RNA loss. In particular, some metals are known to dramatically accelerate rates of RNA hydrolysis under certain conditions (i.e., 37 °C or higher temperatures, 0.15-100 mM metal concentrations). In this study, we investigated the extent to which metals catalyze RNA hydrolysis under environmentally relevant conditions. At ambient temperature, neutral pH, and ∼10 μM metal concentrations, we determined that metals that are stronger Lewis acids (i.e., lead, copper) catalyzed single-stranded (ss)RNA, whereas metals that are weaker Lewis acids (i.e., zinc, nickel) did not. In contrast, double-stranded (ds)RNA resisted hydrolysis by all metals. While lead and copper catalyzed ssRNA hydrolysis at ambient temperature and neutral pH values, other factors such as lowering the solution pH and including inorganic and organic ligands reduced the rates of these reactions. Considering these factors along with sub-micromolar metal concentrations typical of environmental systems, we determined that both ssRNA and dsRNA are unlikely to undergo significant metal-catalyzed hydrolysis in most environmental aqueous systems.

Left ventricular assist devices (LVADs) are widely used in selected patients suffering from end-stage heart failure (HF). However, their large-scale use has been limited in the past by their adverse events rate. With the development of the third LVAD generation characterized by centrifugal pumps, the role and application of LVADs for treating HF patients has globally increased with improving results, better quality of life and survival. This led to a growing need for scientific evidence supporting the large-scale application of this therapy.

Background: Left ventricular assist devices (LVAD) are increasingly used in patients with end stage heart failure. The HeartAssist 5 and aVAD LVADs offer telemetric monitoring capabilities. Here we report our initial single centre experience with the largest telemonitoring cohort of LVAD patients. Methods: Eleven patients (9 males) received a telemonitoring-capable LVAD and were included in our telemonitoring cohort. Waveforms and alarm data were obtained from the telemonitoring system and hospital records were reviewed for clinical data. Results: Mean age at LVAD implantation was 59±5.1 years (mean ± standard deviation). Seven patients had non-ischemic cardiomyopathy and 4 patients had ischemic cardiomyopathy. Median LVEF at implant was 16% (IQR, 15–20%). The total follow-up time was 2,438 patient-days. A total of 6,216 alarm messages were generated in 11 patients. Most common were low flow alarms due to hypovolemia, followed by low flow alarms because of suspected pump thrombosis. One patient died during follow-up, one received a cardiac transplant and one had the LVAD explanted because of pump thrombosis. Pump thrombosis was suspected in 5 patients with 8 episodes of sudden flow decreases and laboratory signs of haemolysis. Conclusions: Real-time telemonitoring of LVAD pump flow, motor speed and power consumption is a promising tool in the follow-up of LVAD recipients. Trending pump flow over hours or days can assist in the early detection of complications, especially flow reductions due to hypovolemia and LVAD thrombosis. Further studies are warranted to delineate the impact of remote monitoring on patients’ prognosis.

The life sciences community is now increasingly leaning on the processing powers of machines to carry out advanced scientific research. So in order to adequately exploit the capabilities of machines in science, the FAIR (Findable, Accessible, Interoperable, Reusable) principles for scientific data management and stewardship have been proposed. These principles are to assist scientists in tweaking their established research routines so as to unlock the true potential of machines and contribute to better science. However, through interviews with key scientist groups implicated by FAIR we have learned that doing what FAIR demands also presents certain epistemic concerns that discourage scientists to trust FAIR. One such concern is the loss of valuable knowledge in the translation of versatile human readable research output to a restricted, machine friendly language to enable machine action (semantic freedom). A second concern is evident in the displacement of human expertise by this increasing reliance on machines and the ensuing loss of knowledge contributed by these displaced experts (expert intuition). Thus, through this article, we highlight how incorporating FAIR also presents an epistemic loss to the scientific community. But the lack of attention given to these concerns by the proponents of FAIR offers scientists who have to abide by FAIR sufficient reason to resist it. We thus propose that while the implementation of FAIR has so far been paternalistic and top-down, such concerns have also made the scientist sceptical. So by initiating a more balanced, open and honest discussion of not just the benefits and promises of FAIR but also such epistemic costs, FAIR could lay to rest reasons for such scepticism and foster trust within the stakeholders of FAIR.

Current research of gene regulatory mechanisms is increasingly dependent on the availability of high-quality information from manually curated databases. Biocurators undertake the task of extracting knowledge claims from scholarly publications, organizing these claims in a meaningful format and making them computable. In doing so, they enhance the value of existing scientific knowledge by making it accessible to the users of their databases. In this capacity, biocurators are well positioned to identify and weed out information that is of insufficient quality. The criteria that define information quality are typically outlined in curation guidelines developed by biocurators. These guidelines have been prudently developed to reflect the needs of the user community the database caters to. The guidelines depict the standard evidence that this community recognizes as sufficient justification for trustworthy data. Additionally, these guidelines determine the process by which data should be organized and maintained to be valuable to users. Following these guidelines, biocurators assess the quality, reliability, and validity of the information they encounter. In this article we explore to what extent different use cases agree with the inclusion criteria that define positive and negative data, implemented by the database. What are the drawbacks to users who have queries that would be well served by results that fall just short of the criteria used by a database? Finally, how can databases (and biocurators) accommodate the needs of such more explorative use cases?

The use of lateral thoracotomy (LT) for implanting left ventricular assist devices (LVADs) is worldwide increasing, although the available evidence for its positive effects compared with conventional sternotomy (CS) is limited. This systematic review and meta-analysis analyzes the outcomes of LT compared with CS in patients undergoing implantation of a centrifugal continuous-flow LVAD. Four databases and 1,053 publications were screened until December 2019. Articles including patients undergoing implantation of a centrifugal continuous-flow LVAD through LT were included. A meta-analysis to compare LT and CS was performed to summarize evidences from studies including both LT and CS patients extracted from the same population. Primary outcome measure was in-hospital or 30-day mortality. Eight studies reporting on 730 patients undergoing LVAD implantation through LT (n = 242) or CS (n = 488) were included in the meta-analysis. Left thoracotomy showed lower in-hospital/30-day mortality (odds ratio [OR]: 0.520, 95% confidence interval [CI]: 0.27-0.99, p = 0.050), shorter intensive care unit (ICU) stay (mean difference [MD]: 3.29, CI: 1.76-4.82, p < 0.001), lower incidence of severe right heart failure (OR: 0.41; CI: 0.19-0.87, p = 0.020) and postoperative right ventricular assist device (RVAD) implantation (OR: 0.27, CI: 0.10-0.76, p = 0.010), fewer perioperative transfusions (MD: 0.75, CI: 0.36-1.14, p < 0.001), and lower incidence of renal failure (OR: 0.45, CI: 0.20-1.01, p = 0.050) and device-related infections (OR: 0.45, CI: 0.20-1.01, p = 0.050), respectively. This meta-analysis demonstrates that implantation of a centrifugal continuous-flow LVAD system via LT benefits from higher short-term survival, less right heart failure, lower postoperative RVAD need, shorter ICU stay, less transfusions, lower risk of device-related infections and kidney failure. Prospective studies are needed for further proof.

Research that benefits the society but could also be applied to disrupt or harm this society is referred to as Dual Use Research (DUR). Although, certain experiments in nuclear physics, technology and engineering have some dual use character, all research conducted in the life sciences carries the potential to be deliberately misused. Minimising the risks and threats to society that are posed by the misuse of such research warrants putting in place mechanisms that caution, safeguard and prepare those that work with DUR. At the inter/national level, instruments to do so include laws and regulations that forbid the misuse of life sciences research techniques to develop weapons of mass destruction. They also restrict and control the exchange of high-risk biological agents and equipment. At the institutional level, efforts to govern DUR are often voluntary and done through codes of conduct, increasing awareness, as well as training members about the dual use potential of their research. This then equips an individual researcher working with such institutions to identify possible misuse of DUR to identify if misuse of and could with which DUR is conducted and it's misuse may be identified. While researchers associated with academic and government funded institutions carefully scrutinise the potential of misuse of DUR, the same is not reflected in privately funded biopharmaceutical institutions. Despite being a significant part of the life sciences community and carrying out extensive DUR only This implies that besides the laws and regulations that govern DUR at the (inter)national level, the biopharmaceutical industry is expected to voluntarily initiate and address dual use concerns at the institutional and individual level. Thus, following an inventory of the various instruments available for the governance of DUR, the approaches adopted by 10 leading companies in the global biopharmaceutical market to address dual use issues were analysed. The results revealed that only 1 out of the 10 companies identified the potential misuse of high risk biological agents and the need to ensure biosecurity within the company. However, there was no explicit mention of dual use issues even though, instruments that deal with other ethical problems encountered by an employee, are in place. Also, owing to insufficient attention given to dual use issues in this industry, there is a serious lack of awareness and expertise that is crucial to dealing with such dilemmas. The surprisingly limited attention given to the dual use dilemma in the biopharmaceutical industry justifies the need for codes and education to raise awareness and motivate efforts towards the ethical resolution of conflicts concerning the misuse of such research.

Pollution has been a common threat to the sustainability of commons resources. While there now exist plenty of safeguards addressing the consequences of pollution on natural resources, little attention has been given to those on the knowledge commons. To understand how pollution occurs and is tackled in the knowledge commons, I take the case of a subset of the life science knowledge commons – the Gene Regulation Knowledge Commons (GRKC). Members from the gene regulation community have come together to work towards a knowledge commons under the Gene Regulation Ensemble Effort for the Knowledge Commons (“GREEKC”). Their efforts have been directed at coordinating and aligning the various practices of data management that prevail across different databases pertaining to gene regulation knowledge. The end goal is to establish a standard framework for knowledge management for GRKC. By examining the polluting practices that arise in the GRKC and how this pollution is alleviated, I claim that here, manually curated databases discern between knowledge that is pure or polluted. However, being a part of the same commons do these databases draw the same distinctions between what is pure and what is polluted? Or do different databases arrive at different conclusions? Is what is pure for one also pure for all?

Introduction: Pump thrombosis of left ventricular assist devices remains a devastating complication with high morbidity and mortality. Despite the improvements made, the matter affects many patients and the treatment options are limited to thrombolysis and surgical replacement. An alternative approach using the aspiration Indigo catheter was tested. Methods: An Indigo thrombectomy catheter was used within an in vitro model to assess the direct aspiration of prefabricated clots from three different positions within the HeartWare HVAD (inlet, outlet, and housing). The experiments were conducted with a straight and an angled catheter. The aspiration pressure was constant. The flow, power consumption, and pressure head of the left ventricular assist devices were measured at pre-defined measuring points. Results: The device was more effective (success rate 71%) at inlet and outlet of the left ventricular assist device. In addition, the duration of aspiration and the aspiration volume were shorter in comparison to the aspiration in the housing (inlet M = 19.75 s, outlet M = 60.50 s, and housing M = 38.75 s). Moreover, the aspiration volume was associated with the aspiration duration and the weight of thrombi but not with their volume. Noteworthy, the angled catheter showed an improved performance compared to the straight one (67%–33%). The recorded parameters showed no major changes during the use of the catheter. After application of the Indigo catheter, flow and pressure head of the pump could be restored. Conclusions: The aspiration system showed promising results under specific conditions for the treatment of pump thrombosis in an in vitro model. However, further examination, including in vivo experiments, will justify its effectiveness.

Chronic end-stage heart failure (CHF) is a major healthcare problem with rapidly growing incidences in Europe and the United States (1). With decreasing cardiac transplant rates worldwide, alternative treatment methods become increasingly important.

Background: Device thrombosis is one of the main complications in left ventricular assist devices (LVAD) therapy and remains a challenging issue. Data on device thrombosis management, especially on the application of direct thrombin inhibitors such as argatroban, is limited and a consensus on thrombosis management has not yet been established. Methods: In this study we analysed retrospective clinical data obtained from 26 patients on VAD therapy who received argatroban for suspected VAD thrombosis, between April, 2012 and February, 2017. Results: Thirteen patients (50%) showed resolution of thrombus after argatroban therapy. Eight of 26 patients (30.8%) were free of thrombotic events 90 days after discharge. Argatroban therapy was unsuccessful in 13 patients of the study cohort, leading to subsequent VAD-exchange. Six of 13 patients with first VAD-exchange had no thrombotic events 90 days after discharge. Six patients (23.1%) suffered from bleeding, especially gastrointestinal bleeding. No hemorrhagic strokes were observed. Three patients (11.5%) did not survive the follow-up period. Conclusions: Argatroban appears to be an alternative to other pharmacological treatment options in VAD thrombosis. Efficacy and safety characteristics are acceptable, but further investigation on larger populations is necessary.

In this article, we present the case of a 72-year-old male patient suffering from a severe form of singular isolated end-stage right heart failure based on arrhythmogenic right ventricular cardiomyopathy (ARVC), who was admitted to our clinic for acute cardiac decompensation.

Polyethylene oxide (PEO) and carboxymethyl cellulose (CMC)/PEO scaffolds are fabricated by electrospinning technique for soft tissue engineering applications. Morphological analysis of the scaffolds reveals formation of stable, regular and cylindrical fibers with 3-D porous interconnected network. Polyelectrolytic nature of CMC results in the formulation of thinner CMC/PEO fibers than pure PEO fibers. All the scaffolds are thermally stable and possess appreciable tensile properties to support cells and promote their growth. The non-toxicity and the ability of the scaffolds to facilitate cell proliferation are supported by MTT assay. This study contributes a promising approach to fabricate scaffolds for possible potential applications in soft tissue engineering applications.

Introduction: Heart failure (HF) is one of the rising problems in the contemporary society with growing incidences of end-stage HF. While heart transplantation (HT) is the gold standard treatment for end-stage HF, its availability is limited by the lack of heart donors. As a consequence, left ventricular assist devices (LVADs) are becoming key therapies as bridge to transplant (BTT) strategy to improve survival and outcomes.Areas covered: A significant advancement for wider applications of LVADs as BTT was facilitated by the introduction of miniaturized pumps such as the HVAD (HeartWare®, Medtronic, MN, USA), allowing intrapericardial implants and less-invasive approaches. In this review article, we describe the technical features of the HVAD and its outcomes in terms of efficacy and safety when implanted as BTT strategy. Moreover, we discuss the postoperative results of HT in HVAD recipients and its application in the pediatric population.Expert opinion: It has been demonstrated that the HVAD positively influences the survival of end-stage HF patients awaiting HT, with an acceptable rate of adverse events. Due to its reduced size, it is particularly suitable for LVAD implantations through lateral thoracotomy and in patients with small thoracic dimensions.

The production of fuels and chemicals from renewable feedstocks is necessary for a fossil fuel independent economy. Lignin and other industrial wastes represent sustainable, non-food feedstocks that can be tapped for microbe-based bioproduction. Rhodococcus opacus is a gram-positive bacterium capable of catabolizing a broad range of feedstocks, and recent technological advances have further established its potential for lignin and industrial waste valorization. In the process of developing R. opacus as a platform for bioproduction, metabolic profiling has elucidated its native mechanisms of bioconversion, adaptive evolution has enhanced its tolerance towards inhibitory feedstocks, and genetic engineering has enabled it to produce novel products, such as wax esters, free fatty acids, and long chain hydrocarbons. Here, we present recent examples of broad feedstock utilization and value-added chemical production by R. opacus, demonstrating its potential as an industrially relevant strain.

In June 2014 the worldwide first implantation of a new and promising Left Ventricular Assist System (LVAS) for end-stage heart failure therapy was performed by Dr. Schmitto and his team at Hannover Medical School, Hannover, Germany (1).

Purpose Despite maximal medican and surgical therapy, the outcomes of severe biventricular failure remain poor with mortality rates of up to 100%. The only definite therapy option for this disease is the total replacement of the heart - either by cardiac transplantation or by total artificial heart (TAH) implantation. Due to the lack of donor organs, mechanical assist devices are the most relevant option for these patients. The permanent availability of mechanical devices is especially attractive in emergency cases as well as in high-risk patients. The placement of two HeartMate 3 in the setting of a TAH is an alternative approach to pulsatile TAH implantation. We now present the worldwide first series of outcomes of this novel procedure. Methods We performed a retrospective analysis of seven consecutive patients who underwent off-label HeartMate 3 TAH implantation after cardiectomy at two international medical institions. Data was acquired using the in-house clinical databases. Follow-up time was thirty days postoperatively. Among perioperative baseline characteristics, adverse events and survival data were collected and analyzed. The retrospective study was approved by the loca institutional ethics committee. Results Out of 7 patients 4 were male (57%). Primary diagnosis was dilated cardiomyopathy in four cases (4/7, 57%) Other diagnoses were stone heart syndrome, restrictive cardiomyopathy and post-partum cardiomyopathy. All patients were previously supported by ECMO. 3 patients suffered from severe ventricular thrombosis. Intraoperative mortality was 0%. One patient was successfully transplanted after 71 days on device. One patient is still on-going on the device, currently discharged and waiting for heart transplantation (POD 259). Full mobility was achieved in both patients. In all cases postoperative hemodynamic stability was successfully achieved. No device related technical complications occured. Four patients died within thirty days of support (51%; POD 10-21). Causes of death were sepsis and multi-organ failure (3/4) and stroke (1/4). Conclusion It has been proven that the implantation of two HeartMate 3 VADs in the settings of a total artificial heart is a feasible concept with no technical adverse events in our patient population. In this high risk patient cohort, a reduction of 30-day-mortality from 100% to 57% was achieved.

Left ventricular assist devices (LVADs) are emerging as the treatment of choice for advanced heart failure due to the dearth of healthy donor hearts for cardiac transplantation. The HeartMate 3 LVAD is a novel centrifugal pump which was developed to provide hemodynamic support in heart failure patients, either as a bridge to transplant (BTT), myocardial recovery, or as destination therapy (DT). Technological and clinical advancements have led to optimized hemocompatibility and development of less invasive surgical procedures for the implantation of this pump. The worldwide first implantation of the HeartMate 3 was performed by Prof. Schmitto and his team at Hannover Medical School, Germany in 2014, paving the way for subsequent surgical developments. This article summarizes the advanced technological and clinical aspects of the HeartMate 3 and outlines future technical developments for safe and effective treatment of advanced heart failure.

Although rare, recovery of cardiac function after mechanical support of the left ventricle is the most desirable therapeutic goal in the treatment of end-stage heart failure.Herein, we present a novel implantable device for explantation of the HeartMate 3™ left ventricular assist device (LVAD) in patients, following cardiac recovery, avoiding (re-) sternotomy.This article demonstrates the feasibility of applying this novel device, which fits into the sewing ring of the LVAD.This custom-made mechanical plug offers a promising alternative to standard device-explantation procedures.

Background End-stage heart failure is associated with severe after-effects such as heart valve insufficiency, cardiac arrhythmias or end-organ dysfunctions. Renal failure or 'cardiorenal syndrome' is a critical end-organ disorder associated with advanced heart failure, which occurs due to low-output failure. Drug therapy or surgical interventions involving left ventricular assist device (LVAD) implantation may impede the progress of heart insufficiency and its after-effects including renal failure. In this study, we investigated the impact of a minimally invasive ventricular assist device implantation through upper hemisternotomy combined with anterolateral thoracotomy on renal function, in patients with perioperative renal failure. Methods We analyzed data obtained from 103 patients (80 males, 23 females; mean age 53.8±11.7) who underwent LVAD implantation at our clinic within a 15-year interval (2001-2016) and were dialyzed due to renal dysfunction. 90 patients were operated with the conventional LVAD implantation technique (standard approach surgery, SAS) and 13 underwent less invasive approach implantation (less invasive surgery, LIS). Results For all patients, data analysis showed significant increase of glomerular filtration rate (GFR) (44.2±56.48 mL/min; 95% CI: 33.81-55.28; P

Background: Functional mitral valve regurgitation is a frequent consequence of left ventricular dysfunction in patients with severe heart failure and is associated with a poor prognosis. It is hypothesized that in this patient group the mitral valve repair, respectively replacement, improves hemodynamics and clinical symptoms. As operative interventions with the help of heart-lung-machine are high risk procedures in these cases, the transcatheter mitral repair with MitraClip ® (Abbott Vascular, IL, USA) has recently become frequently used. Most of these cases experience a progress in left ventricular dysfunction, which finally leads to in an implantation of a left ventricular assist device. In this report, we describe a series of six cases in which patients with end stage heart failure and consecutive functional mitral valve regurgitation were supported with a left ventricular assist device after MitraClip implantation. We aimed to investigate, whether the MitraClip implantation leads to an improvement of the hemodynamic prior left ventricular assist device (LVAD)-implantation. Methods: We retrospectively analyzed the data of 6 patients (5 males, 1 female) with severe heart failure, who underwent LVAD implantation after the MitraClip procedure. The mean age at MitraClip procedure was 64.6 years, mean age at time of LVAD implantation was 65.5 years. The parameters examined were cardiac index (CI), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and the pulmonary capillary wedge pressure (PCWP). Results: All patients had functional mitral regurgitation (MR). Severity of MR was reduced successfully in all treated patients. All patients were discharged with MR I-II and NYHA functional class III or IV after MitraClip procedure. The mean CI was 2.93 before MitraClip procedure and 2.36 before LVAD-Implantation. Mean LVEDD was 71 mm before MitraClip, mean LVEDD was 70.6 mm before LVAD, and 63.2mm after LVAD implantation respectively. The mean PCWP was 21.5 mmHg before MitraClip and 19.8 mmHg before LVAD implantation respectively. The mean left ventricular ejection fraction (LVEF) was 19.2% before MitraClip, the mean LVEF was 17.6% before LVAD and 15 % after LVAD implantation. Two of the LVAD implanted patients died due to post-operative complications. There were no complications after MitraClip procedure. Conclusions: Our presented patient cohort presented little hemodynamic improvement after the MitraClip procedure. There was no clinical benefit for the patients after MitraClip procedure, progressing left ventricular dysfunction could not be prevented and resulted in subsequent LVAD implantation.

Background: Driveline infection (DLI) is one of the leading causes for unplanned re-admissions of patients undergoing therapy with left ventricular assist devices (LVAD). In previous studies our group was able to show that a double tunneling implantation technique could significantly reduce infection rates one year after implantation. We now report the results of the five-year-follow up of patients receiving the double tunneling technique. Methods: We retrospectively analyzed patients receiving LVAD therapy with the HeartWare ventricular assist device (HVAD) (Medtronic, Minnesota, MN, USA) LVAD. For 36 patients (group 1) the driveline was tunneled via a conventional technique. In the remaining 33 patients (group 2) the drivelines were implanted by means of a double tunneling technique. The double tunnel driveline technique involved placement of the driveline in the sheath of the rectus muscle in the umbilical direction and then subcutaneously to the left (alternatively right) upper quadrant. We retrospectively compared both groups. Primary outcome parameters were infection rate and mortality. Results: Five years after LVAD implantation the DLI rate of patients operated by a double tunneling technique was significantly lower than in the conventional technique group [61% (n=22) group 1 vs . 30% (n=10) group 2, P=0.004]. The 5-year mortality was lower in group 2 [42% (n=15) group 1 vs . 27% (n=9) group 2] but did not achieve statistical significance (P=0.10). The days of LVAD support between the two groups were comparable (1,275.56±885.89 group 1 vs . 1,321.94±711.37 group 2). The tunnel technique itself showed to be strongly associated with the occurrence of DLI. Other elevated variables are liver disease and dilated cardiomyopathy as primary disease. Conclusions: Double tunneling technique for driveline implantation leads to significantly lowered infection rates after 5 years of LVAD therapy and it is associated with a lower mortality.

Background: Pump thrombosis is the most severe and acute complication of left ventricular assist device (LVAD) therapy and treatment remains challenging. Whilst lysis therapy is often not successful, the exchange of the occluded LVAD is currently the most applied therapeutic treatment for this event. With this study we examine the effects of minimal-invasive LVAD exchange on the rate re-thrombosis and outcomes as well as adverse events in the study group. Methods: Between February 2004 and December 2015 more than 600 LVADs were implanted at our institution. We retrospectively studied a patient cohort of 41 patients who underwent LVAD exchange because of pump thrombosis at a single institution. Outcomes, rates of re-thrombosis and adverse events were analyzed. Results: Between February 2004 and December 2015, 87 exchanges of LVADs were performed at a single center. In 41 cases pump thrombosis was the reason for LVAD exchange. A total of 28 patient years (10,276 days) were analyzed. Average ICU stay was 15.8±20.4 days and average in-hospital stay 38.1±37.3 days after LVAD exchange. After thirty days the survival rate was 80.5%, 75.6% after 6 months and 70.7% one year after LVAD exchange. Out of the study cohort, three patients have successfully undergone heart transplantation. Twelve patients suffered a stroke postoperatively (29%). Twelve patients needed postoperative dialysis (29%). No technical complications of the VAD were recorded in the study group. Two patients underwent successful LVAD explantation due to myocardial recovery. One year after LVAD exchange, 14 patients underwent re-exchange due to pump thrombosis (34%). Eight patients suffered from a LVAD related infection out of which two patients were treated by pump exchange. A total of 12 patients died during the complete one year follow up of this study (29%). Four patients died in the second, two in the third and one in the fourth year after LVAD exchange. The remaining 17 patients are still ongoing on the device. Conclusions: It is generally feasible to treat pump thrombosis via LVAD exchange. Yet, the exchange procedure is not without risk and the risk of re-thrombosis (34%), stroke (29%), postoperative dialysis (29%) and perioperative complications remains high.

Growing worldwide incidences of end-stage heart failure and declining rates of cardiac transplants have given rise to the need for alternative treatment options, based on mechanical circulatory support (MCS) devices such as left ventricular assist devices (LVADs). Technologically advanced LVADs such as the HVAD® (HeartWare®, Medtronic) facilitate safe and efficient treatment of heart failure patients with reduced post-operative complications, which is attributed to their considerably miniaturized size. This also facilitates the development and implementation of novel, minimally-invasive surgical techniques. The HVAD is a centrifugal pump, manufactured by HeartWare Inc., (Framingham, MA, USA) and subsequently by Medtronic Inc., (Minnesota, MN, USA), and has been approved for clinical application after receiving the CE Mark approval in 2008 and the FDA approval in 2012. Current research efforts are focused on further miniaturization alongside optimization of electronic and software controllers as well as implementation of the transcutaneous energy transfer (TET) technology. Salient features of the HVAD pump technology, clinical applications and future optimization strategies have been discussed in this article.

Background: Left ventricular assist device (LVAD) (HVAD, Medtronic, Minneapolis, MN, USA) implantation is already a widely accepted treatment option for end-stage heart failure (HF) but also still considered as a rescue therapy for patients suffering from cardiogenic shock. Standard LVAD implantation techniques are often associated with high mortality rates and can result in severe complications, like bleeding or right heart failure (RHF). The aim of our study was to assess the outcome of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 1 patients (so called “crash and burn” patients) undergoing a LVAD implantation by standard or less invasive surgery. Methods: We performed a retrospective evaluation of the 1-year outcome of 32 consecutive HF patients in cardiogenic shock, who underwent LVAD implantation in our institution. A total of 32 INTERMACS 1 patients were emergently operated. Fourteen patients (group A) were operated by using the “Hannover-VAD-technique”, which is widely known to be less invasive (upper hemisternotomy and a left-sided anterolateral thoracotomy). In contrast, 18 patients (group B) were implanted with LVAD by using the standard technique (full sternotomy). The primary endpoint was survival after 1 year without device-related re-operations. Secondary endpoints included combined analyses of rates of RHF, respiratory failure and bleeding during the trial period. Results: Baseline characteristics were similar in both groups. Survival after 1 year was higher in group A (69.7% vs. 50.0%). Technique-related adverse events (AEs) were also lower in the minimally invasive group, including a lower RHF (35.7% vs. 61.1%) and of further postoperative bleeding requiring surgery (14.3% vs. 33.3%). Conclusions: LVAD surgery in INTERMACS 1 patients is associated with remarkably good outcome considering the already very high mortality of those patients, and compared to previously reported surgical outcomes. Our study indicates that minimally invasive LVAD implantation in cardiogenic shock decreases mortality and the incidence of postoperative AEs.

Cardiovascular diseases are the leading cause of mortality rates throughout the world. Next to an insufficient number of healthy donors, this has led to increasing numbers of patients on heart transplant waiting lists with prolonged waiting times. Innovative technological advancements have led to the production of ventricular assist devices that play an increasingly important role in end stage heart failure therapy. This review is intended to provide an overview of current implantable left ventricular assist devices, different design concepts and implantation techniques. Challenges such as infections and thromboembolic events that may occur during LVAD implantations have also been discussed.

Cardiovascular diseases are the leading cause of mortality rates throughout the world. Next to an insufficient number of healthy donors, this has led to increasing numbers of patients on heart transplant waiting lists with prolonged waiting times. Innovative technological advancements have led to the production of ventricular assist devices that play an increasingly important role in end stage heart failure therapy. This review is intended to provide an overview of current implantable left ventricular assist devices, different design concepts and implantation techniques. Challenges such as infections and thromboembolic events that may occur during LVAD implantations have also been discussed.

In 2014, Facebook and Apple announced that they would pay for female employees to have their oocytes frozen to allow them to delay having children and instead focus on their careers. Whatever motivated the companies to make their offers, the fact that they did so highlights a prevalent problem faced by many young women: Their most fertile years are also a crucial period for building a career, when time off work may disadvantage them. > … cryopreservation is known to affect cell survival after thawing, which can have an impact on the subsequent clinical applications of frozen cells. To fulfill their offers, Facebook and Apple will need to offer their employees access to cryopreservation technologies that profoundly change the dynamics of family planning. Such technologies are not new, but work over the past decades has been aimed at increasing safety and efficacy and has reduced costs to the point that companies can now offer cryopreservation as a way to attract and retain female workers. Of course, the potential of cryopreservation goes far beyond freezing the eggs or sperm of ambitious young technology workers—it is a ubiquitous technology used in research and medicine for a wide variety of applications (Fig 1). For example, cryopreservation is used to store and transport biological material, including adult stem cells or stem cells from umbilical cord blood or bone marrow—both of which can later be used to treat disease or extend lifespan in the same patient—blood donations, especially of rare blood types, tissues, and organs. It is also offered as a crucial service for cancer patients to preserve their gametes before they undergo therapy that may render them infertile and, generally used in assisted reproduction to store oocytes, fertilized eggs, or embryos. Cryopreservation can contribute to environmental preservation efforts, where it is used to conserve the …

Porous and cytocompatible silicon carbide (SiC) ceramics derived from wood precursors and coated with bioactive hydroxyapatite (HA) and HA-zirconium dioxide (HA/ZrO2) composite are materials with promising application in engineering of bone implants due to their excellent mechanical and structural properties. Biomorphic SiC ceramics have been synthesized from wood (Hornbeam, Sapele, Tilia and Pear) using a forced impregnation method. The SiC ceramics have been coated with bioactive HA and HA/ZrO2 using effective gas detonation deposition approach (GDD). The surface morphology and cytotoxicity of SiC ceramics as well as phase composition and crystallinity of deposited coatings were analyzed. It has been shown that the porosity and pore size of SiC ceramics depend on initial wood source. The XRD and FTIR studies revealed the preservation of crystal structure and phase composition of in the HA coating, while addition of ZrO2 to the initial HA powder resulted in significant decomposition of the final HA/ZrO2 coating and formation of other calcium phosphate phases. In turn, NIH 3T3 cells cultured in medium exposed to coated and uncoated SiC ceramics showed high re-cultivation efficiency as well as metabolic activity. The recultivation efficiency of cells was the highest for HA-coated ceramics, whereas HA/ZrO2 coating improved the recultivation efficiency of cells as compared to uncoated SiC ceramics. The GDD method allowed generating homogeneous HA coatings with no change in calcium to phosphorus ratio. In summary, porous and cytocompatible bio-SiC ceramics with bioactive coatings show a great promise in construction of light, robust, inexpensive and patient-specific bone implants for clinical application.

Effective cryopreservation protocols are essential for long-term storage of cells and their subsequent clinical application. Freezing protocols are generally considered as safe; however, putative effects on epigenetic marks have not yet been studied in detail. While post-thaw cell survival rates have been used to evaluate the success of cryopreservation protocols, increasing evidence suggests that freezing may be associated with deviations from the physiological epigenetic marks with putative long-term effects on the cells and/or their derivatives. A better understanding of the underlying mechanisms would be beneficial for improving safety and effectiveness of freezing protocols. The purpose of this review is to provide current information regarding epigenetic alterations (DNA methylation and histone modification patterns) associated with cryopreservation.

A high survival rate of cryopreserved cells requires optimal cooling and thawing rates in the presence of a cryoprotective agent (CPA) or a combination of CPAs in adequate concentrations. One of the most widely used CPAs, dimethyl sulfoxide (Me2SO), however is toxic at high concentrations and has detrimental effects on cellular functions. Additional processing steps are necessary to remove the CPA after thawing, which make the process expensive and time consuming. Therefore it is of great interest to develop new cryoprotective strategies to replace the currently used CPAs or to reduce their concentration. The aim of this study was to investigate if thermal activation of human pulmonary microvascular endothelial cells (HPMEC ST-1.6R), prior to cryopreservation, could improve their post-thaw viability since the resulting heat shock protein expression acts as an intrinsic cellular protection mechanism. The results of this study suggest that both heat and cold shock pretreatments improve cryopreservation outcome of the HPMEC ST-1.6R cells. By re-cultivating cells after heat shock treatment before cryopreservation, a significant increase in cellular membrane integrity and adherence capacity could be achieved. However a combination of thermal activation and cryopreservation with alternative CPAs such as ectoine and L-proline could not further enhance the cell viability. The results of this study showed that pretreatment of endothelial cells with thermal activation could be used to reduce the Me2SO concentration required in order to preserve cell viability after cryopreservation.

BACKGROUND: People of border areas are socio‑economically underdeveloped and medically underserved. Anemia in the growing phase of life impairs the physical and cognitive functions and in turn, hampers the overall development of the country. OBJECTIVE(S): To find out the prevalence, socio‑demographic correlates, and risk factors of anemia among adolescents residing in a border area. MATERIALS AND METHODS: A community‑based descriptive cross‑sectional study was carried out among 370 adolescents selected randomly by multistage and 30‑clusters random sampling method. Data pertaining to the socio‑demographic factors, life style and diet pattern, relevant health problems, and care‑seeking were collected by a pre‑designed schedule. Venous blood was examined by cyanmethemoglobin method to assess the Hemoglobin level. RESULTS: The overall prevalence of anemia was revealed to be 83.78% with a significant female predilection (92.59% vs. 76.92%, χ2 = 16.46 at degree of freedom = 1, P < 0.05; odds ratio (OR) = 3. 75, 95% confidence interval (CI) = 1.84‑7.77). The prevalence was higher among early adolescents compared with mid- and late-adolescents (χ2 (overall) = 9.14, at df=2, P = 0.0103) but significant female preponderance was found in the last group with χ2 = 12.5, df = 1, P < 0.05; OR(CI) = 4.29 (1.73-11.02). Anemia was revealed to be associated with lower literacy and socio-economic status (P < 0.05), bare-foot walking (P < 0.05), open-field defecation (P < 0.05), worm-infestation (P < 0.05), and care-seeking from unauthorized medical practitioners (P < 0.05) . CONCLUSION: Strict implementation of the National Anemia Control Programme as a component of school health and other health services through sub‑centers and Anganwadi Centers is the need of the moment to chain the anemia.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells and have diverse potential biomedical applications such as in tissue repair, transplantation and cell-based therapies. Cryopreservation of MSCs allows long term storage of these cells and therefore plays a crucial role in their subsequent applications. The success of a cryopreservation protocol is often assessed by analyzing the survival rates of thawed cells. However this parameter does not provide information on the possible adverse cellular effects of cryopreservation, such as on gene expression regulation and cell fate decisions. Treatment with Me 2 SO has been shown to impact the histone modification patterns and the DNA methylation patterns of various tissues. Histone modifications and DNA methylation are epigenetic mechanisms that regulate eukaryotic transcription without altering the DNA sequence. Epigenetic mechanisms play an important role in stem cell maintenance and differentiation and when deregulated may lead to the formation of diseases like cancer. Despite the widespread cryopreservation of MSCs with Me 2 SO, the effects of cryopreservation on the epigenetic mechanisms of MSCs are yet to be fully evaluated. In the current study bone marrow derived-MSCs from the common marmoset monkey were frozen with different concentrations of Me 2 SO using a controlled-rate freezing device. Post-thaw cell viability was examined by analyzing the membrane integrity (by trypan blue staining) and mitochondrial dehydrogenase activity (using MTT assay). The functional integrity of cryopreserved MSCs was tested by analyzing their ability to differentiate into adipogenic and osteogenic lineages. The global acetylation and methylation patterns of the different histone proteins were analyzed using immunocytochemistry and mass-spectrometry. Results indicated that the survival, differentiation ability and modification patterns of various histone proteins in mesenchymal stem cells may be altered after cryopreservation, depending on the concentration of Me 2 SO used for cryopreservation.

Objectives Cryopreservation plays an important role in the long-term storage of cells and tissues. A high survival rate is a function of optimal cooling rate, appropriate cryoprotective agent (CPA) and its adjusted concentration. The most widely used CPA, dimethyl sulfoxide (Me2SO), however is toxic at high concentrations and has detrimental effects on the biological functioning of a cell. Therefore, it is of great interest to develop new cryoprotective strategies to replace currently used CPAs or to reduce their concentration. Since one of the major damaging factors is the occurence of ROS during and after thawing we have investigated the addition of ascorbic acid and α-tocopherol as potential antioxidants. Methods Mesenchymal stem cells (MSC) of the common marmoset monkey were frozen in 200 μl PCR-tubes (5x105 cells/ml) with optimal cooling rate (Pogozhykh et al., Reg. Med. 6 (6s2) (2011) 229) in a μ-freezer device. Different concentrations of ascorbic acid (50, 100 and 250 mM) and α-tocopherol (100, 200 and 500 μM) were studied exclusive or in combination and with Me2SO (2,5 and 5% v/v). Cells attached to the culture flask surface after 24 h recultivation were considered as viable, the survival rate was compared to that of cells frozen with Me2SO as positive control. Surviving cells were further tested for differentiation capability. Results The addition of α-tocopherol improved the survival of primate MSCs after cryopreservation even with 2,5% Me2SO. With 100 μM α-tocopherol and 5% Me2SO survival was more than two fold higher than with 5% Me2SO alone. Ascorbic acid had no considerable effect on the survival rate of MSCs but in combination with tocopherol its addition stabilized the positive effects. Intracellular lipid vesicles were clearly stained by Oil Red O and proved the adipogenic differentiation capability of marmoset MSCs after cryopreservation with antioxidant addition. Conclusions: Accessory application of α-tocopherol and ascorbic acid improved survival and proliferation of MSCs from the marmoset monkey after cryopreservation. Me2SO could be reduced to moderate concentrations. These findings will help to avoid epigenetic modifications caused by Me2SO which preliminary results showed. We thank L. Smits, S. Huper and M. Abbetmeier-Basse for their outstanding technical assistance. Source of funding: This work is supported by funding from the Deutsche Forschungsgemeinschaft for the Cluster of Excellence REBIRTH (EXC 62/1). Conflict of interest: None declared. hofmann@imp.uni-hannover.de