Rosai-Dorfman disease (RDD) is a rare non-malignant histiocytosis disorder, commonly manifesting with massive painless cervical lymphadenopathy. Renal involvement develops in only four percent of patients with RDD. Generally, RDD is self-limiting and has a good prognosis; however, in patients with renal involvement, mortality rate can be as high as 40%.

Aging is an inevitable process caused by the accumulation of degenerative destructions, which ultimately leads to organism death. As the aging process occurs at the molecular, cellular, and tissue levels, understanding the whole details is the prerequisite for the development of anti-aging therapy. More than 300 compounds of different sources have been reported with the anti-aging activity that slow aging and extend lifespan through regulating single or multiple signaling pathways. Recent innovations in nanotechniques could lead to the development of nanomaterials having anti-aging effects or acting as nanocarrier systems and distributers of anti-aging drugs. In this review, we summarized the molecular mechanisms of longevity and the prospect of developing anti-aging nanomaterials targeting aging pathways.

Microfluidic technology is a science and technology that can accurately manipulate fluids in micro-sized channels. In recent years, microfluidic devices have attracted wide attention due to its easy manipulation, miniaturized size, high throughput and precise control, which provide a potential platform for antibody screening. This review paper provides an overview of recent advances in microfluidic methods application in the field of antibody preparation. While hybridoma technology and four antibody engineering techniques including phage display, single B cell antibody screening, antibody expression and cell-free protein synthesis are mainly introduced, important advances of experimental models and results are also discussed. Furthermore, the authors expound on the limitations of current microfluidic screening system and present future directions of antibody screening platform based on microfluidics. Antibody preparation on microfluidics combined with other technologies has huge application potential in the field of biomedicine, and it is anticipated to be further developed.

A non-refined, organic pumpkin seed oil (PSO) was chosen for the isolation and structure verification of the rare vitamin E compound γ-tocomonoenol (γ-T1). Initial measurements indicated the presence of ~0.4 mg γ-T1 per 100 g pumpkin seed oil. Saponification of ~2 L pumpkin seed oil, followed by repeated countercurrent chromatography (CCC) with the solvent system n-hexane/benzotrifluoride/acetonitrile (10:3.5:6.5, v/v/v) and silica gel column chromatography enabled the isolation of 6.8 mg γ-T1 with a purity of 96.0%. Structural analysis by 1H NMR spectroscopy and gas chromatography with mass spectrometry (GC/MS) of the γ-T1 isolate confirmed the presence of a double bond in C-11´-position (11´-γ-tocomonoenol). Next to γ-T1, CCC fractionation enabled the detection of 18 different tocochromanols, many of which were reported for the first time in pumpkin seed oil. This unmatched variety covered among others α-/γ-tocopherol, α-/γ-tocomonoenol, two α- and two γ-tocodienol isomers, α-/γ-tocotrienol as well as the rare 11´-β-tocomonoenol (β-T1) and δ-T1. Three uncommon tocochromanols were also detected whose origins and structure remained unclear.

Abstract: The contour feathers of water birds are well-known to show structural details in their distal one-third that optimally confer water repellency and resistance to water penetration. In this study, these details were further examined to see if they also provide resistance to the impact forces of diving and alighting. To this end, 49 species representing 37 water bird families were grouped into nine foraging niches before measurement of length, diameter, and spacing of their barbs. Twelve land bird species grouped into two foraging niches were included in this study for comparison. These measurements allowed the calculation of the ranges and medians for barb stiffness and vane deflection for each foraging niche. A phylogenetic ANOVA approach was followed to determine if the foraging niches for water and land birds explain differences in feather microstructure while accounting for phylogenetic relationships. There were no significant group aggregations for water or land birds confirming the statistical reliability of the ANOVA approach. Differences between the deflection parameter medians of water and land bird foraging niches proved significant demonstrating an evolutionary distinction between these groups. No such difference was observed for the two land bird foraging niches indicating similarity in feather structure. For the water birds, significance was found among all aquatic niches showing that differences in feather microstructure are associated with respect to differences in aquatic feeding niches. These findings support the notion that evolutionary adaptations of feather traits are significant across bird species and their respective foraging niches. The observed mechanical and morphological variations of feathers are therefore considered adaptations to different habitats and behavioral patterns.

IntroductionImplantable cardioverter-defibrillators (ICDs) for cardiac resynchronization therapy (CRT-D) with the capability of LV sensing enable the assessment of interventricular delays in ventricular (VT) and supraventricular tachycardias (SVT).Methods and ResultsIn total, 1078 EGM recordings of VT or VF episodes were investigated that have been transmitted via Home Monitoring. Only those EGM recordings showing the onset of the tachyarrhythmia were used for investigation. In the 623 cases eligible for evaluation leftsided VTs could be identified in 349 cases, right-sided VTs in 252 cases. SVTs with a 1:1 antegrade conduction were found in 22 cases. VT can present three different interventricular delays whereby the right-ventricular sensed event (RVs) is either preceding the left-ventricular sensed event (LVs), or the LVs is preceding RVs, or there can be a simultaneous occurrence of RVs and LVs. In SVTs, either the LVs events were delayed or occurred simultaneously with the RVs events. SVT cases with LVs preceding the RVs events were not found.ConclusionThe LV-EGM channel enables to distinguish between left- and right-sided premature ventricular complexes. The assessment of the interventricular delay in VTs is useful to differentiate between a possible apical-, left- or right-sided origin of the VT but not to identify SVTs.

Background: This study evaluated outcomes of cardiac operations with very prolonged cardiopulmonary bypass (CPB) times. Methods: This was a retrospective study of cardiac surgical procedures with very-long CBP times (≥300 minutes) performed at a single institution. Primary outcomes of operative (≤30-day) and one-year mortality were evaluated, and secondary outcomes included use of mechanical support and postoperative complications. A probability analysis was also conducted to identify the correlation between operative mortality and CPB time. Results: 293 patients were included with a Society of Thoracic Surgeons predicted risk of mortality of 2.51% (IQR 1.32%- 4.70%), and median CPB time of 340 minutes (IQR 315.0-385.0). Preoperative mechanical support included intra-aortic balloon pump (IABP, n=4, 1.4%), Impella (n=0), or extracorporeal membrane oxygenation (ECMO, n=2, 0.7%). Intraoperative and operative mortality were 5.1% and 22.5%, respectively. Intraoperative or postoperative mechanical support were utilized in 90 (30.7%) cases, including IABP (n=65, 22.2%), Impella (n=2, 0.68%), or ECMO (n=23, 7.8%). Postoperative complications included prolonged mechanical ventilation (n=121, 41.3%), renal failure (n=71, 24.2%), stroke (n=20, 6.8%), and reoperation (n=95, 32.4%). One-year survival for the overall cohort was 61.4%. Probability analysis identified a CPB time of 446 minutes to be associated with 50% odds of operative mortality. Conclusions: Cardiac operations requiring very-long CPB times are associated with high rates of operative mortality and morbidity, with a 50% operative mortality rate predicted for those with a CPB time of 446 minutes or longer. Nonetheless, the majority of patients survive at least 1 year, and these cases should not be considered futile.

The surgical management of truncus arteriosus poses a constant challenge for the cardiac team treating the patient. A correct diagnosis, surgical therapy and postoperative management are crucial for the survival of the patient. Almost 30% of the patients show an abnormal number of leaflets in the truncal valve, the majority being quadricuspid valves. Additionally, around 25% of the patients show some degree of truncal valve incompetence. We demonstrate an effective way to reconstruct incompetent, quadricuspid valves with good postoperative outcome.

Background: Catheter ablation for atrial fibrillation (AF) treatment provides effective and durable pulmonary vein isolation (PVI) and is associated with encouraging clinical outcome. A novel CF sensing temperature-controlled radiofrequency (RF) ablation catheter allows for very high-power short-duration (vHP-SD, 90W/4 seconds) ablation aiming a potentially safer, more effective and faster ablation. We thought to evaluate preliminary safety and efficacy of vHP-SD ablation for PVI utilizing a novel vHP-SD catheter. The data was compared to conventional power-controlled ablation index (AI) guided PVI utilizing conventional contact force (CF) sensing catheters. Methods and Results: Fifty-six patients with paroxysmal or persistent AF were prospectively enrolled in this study. Twenty-eight consecutive patients underwent vHP-SD based PVI (vHP-SD group) and were compared to 28 consecutive patients treated with conventional CF-sensing catheters utilizing the AI (control group). All PVs were successfully isolated using vHP-SD. The median RF ablation time for vHP-SD was 338 (IQR 286, 367) seconds vs control 1580 (IQR 1350, 1848) seconds (p<0.0001), the median procedure duration was vHP-SD 55 (IQR 48-60) minutes vs. control 105 (IQR 92-120) minutes (p<0.0001). No differences in periprocedural complications were observed. Conclusions: This preliminary data of the novel vHP-SD ablation mode provides safe and effective PVI. Procedure duration and RF ablation time were substantially shorter in the vHP-SD group in comparison to the control group.

Acidithiobacillus ferrooxidans are acidophilic chemolithoautotrophs that are commonly reported to exhibit diauxic population growth behavior where ferrous iron is oxidized before elemental sulfur when both are available, despite the higher energy content of sulfur. We have discovered sulfur dispersion formulations that enables sulfur oxidation before ferrous iron oxidation. The oxidation of dispersed sulfur can lower the culture pH within days below the range where aerobic ferrous iron oxidation can occur so that ferric iron reduction occurs which had previously been reported over extended incubation periods with untreated sulfur. Therefore, we demonstrate that this substrate utilization pattern is strongly dependent on the cell loading in relation to sulfur concentration, sulfur surface hydrophobicity, and the pH of the culture. Our dispersed sulfur formulation, lig-sulfur, can be used to support the rapid antibiotic selection of plasmid-transformed cells, which is not possible in liquid cultures where ferrous iron is the main source of energy for these acidophiles. Furthermore, we find that media containing lig-sulfur supports higher production of green fluorescent protein (GFP) compared to media containing ferrous iron. The use of dispersed sulfur is a valuable new tool for the development of engineered A. ferrooxidans strains and it provides a new method to control iron and sulfur oxidation behaviors.

In this work we study the existence of positive solutions to the following fractional elliptic systems with Hardy-type singular potentials, and coupled by critical homogeneous nonlinearities \begin{equation*} \begin{cases} (-\Delta)^{s}u-\mu_{1}\frac{u}{|x|^{2s}}=|u|^{2^{\ast}_{s}-2}u+\frac{\eta\alpha}{2^{\ast}_{s}}|u|^{\alpha-2} |v|^{\beta}u+\frac{1}{2}Q_{u}(u,v) \ \ in \ \Omega, \\[2mm] (-\Delta)^{s}v-\mu_{2}\frac{v}{|x|^{2s}}=|v|^{2^{\ast}_{s}-2}v+\frac{\eta\beta}{2^{\ast}_{s}}|u|^{\alpha} |v|^{\beta-2}v+\frac{1}{2}Q_{v}(u,v) \ \ in \ \Omega, \\[2mm] \ \ u, \ v>0 \ \ \ \ \ in \ \ \Omega, \\[2mm] \ u=v=0 \ \ \ \ in \ \ \mathbb{R}^{N}\backslash\Omega, \end{cases} \end{equation*} where $(-\Delta)^{s}$ denotes the fractional Laplace operator, $\Omega\subset\mathbb{R}^{N}$ is a smooth bounded domain such that $0\in\Omega$, $\mu_{1}, \mu_{2}\in [0,\Lambda_{N,s})$, $\Lambda_{N,s}=2^{2s}\frac{\Gamma^{2}(\frac{N+2s}{4})}{\Gamma^{2}(\frac{N-2s}{4})}$ is the best constant of the fractional Hardy inequality and $2^{*}_{s}=\frac{2N}{N-2s}$ is the fractional critical Sobolev exponent. In order to prove the main result, we establish some refined estimates on the extremal functions of the fractional Hardy-Sobolev type inequalities and we get the existence of positive solutions to the systems through variational methods.

In this study we adapted WRF-Hydro to the Cape Fear River basin (CFRB) to assess its performance during Hurricane Florence (2018). The model was first calibrated with a strategy of mixture of automatic and manual calibration during Florence and then evaluated with an independent hurricane event. With satisfactory NSE values (>0.4) achieved at all gages for hourly simulation, the model demonstrates its potential in simulating the flood response at both basin and sub-basin scale during hurricane events. The model’s capability in reproducing rainfall and properly translating it to hydrological response was further evaluated. The analysis suggests that the calibrated WRF-Hydro in combination with a series of WRF simulation using different microphysics schemes can provide reasonable flood simulations. The model reproduced peak streamflow observed at gage stations with acceptable errors in timing and amplitude. Meanwhile, positive(negative) bias in rainfall input is likely to be amplified (reduced) in streamflow forecast when simulated rainfall volume is larger than the “model true”. And the timing bias mostly inherited from rainfall simulation and calibration process.

Central vision loss, photopsia, floaters and macular edema in a highly myopic patient can easily be misrelated to high myopia complications. However, in atypical cases, detailed examination along with a thorough diagnostic is required to establish the right diagnosis, which is often beyond the limits of the condition originally considered.

Aims: The objective of this retrospective cohort study was to provide an overview of the utilization of originator and biosimilar infliximab in the Netherlands. Methods: All infliximab dispensings were selected from the PHARMO In-patient Pharmacy Database from 2002-2018. Descriptive analyses were performed in order to characterise initiators and to describe switching patterns over time. Results: Overall, 3,840 patients with 61,274 infliximab dispensings were identified. 2,496 patients initiated an originator infliximab and 777 patients initiated a biosimilar infliximab. Overall, 57% of the patients was female and mean age was 43.2 years. Both originators and biosimilars were mostly prescribed by gastroenterologists, followed by internists and rheumatologists. After market authorization of the first biosimilar the proportion of new patients initiating the biosimilar increased from 39% in 2015 to 91% in 2018. Out of 704 patients eligible for switching 34% switched. Among switchers, the proportion of females was 60% and mean age at index was 45.1 years. Among non-switchers, 55% was female and mean age was 39.8 years. The median time to switch was 1.7 years and switchers were most frequently initiated on infliximab by a rheumatologist (42%), while non-switchers were most frequently initiated by a gastroenterologist (42%). Conclusions: The results of this large population-based cohort show an increase in biosimilar initiation in daily clinical practice. The number of switchers remains relatively low as non-medical switch is not encouraged in the Netherlands.

Seagrasses play a vital role in structuring coastal marine ecosystems, but their distributional range and genetic diversity have declined rapidly over the past decades. In order to improve conservation of seagrass species, it is important to predict how climate change may impact their ranges. Such predictions are typically made with correlative species distribution models (SDMs), which can estimate a species’ potential distribution under present and future climatic scenarios given species’ presence data and climatic predictor variables. However, these models are typically constructed with species-level data, and thus ignore intraspecific genetic variability of populations that potentially have adaptations to heterogeneous climatic conditions. Here, we explore the link between intraspecific adaptation and niche differentiation in Thalassia hemprichii, a seagrass broadly distributed in the tropical Indo-Pacific Ocean and a crucial provider of habitat for numerous marine species. Using microsatellite-based genotyping, we identified two distinct phylogeographical lineages within the nominal species and found an intermediate level of differentiation in their multidimensional environmental niches, suggesting the possibility for local adaptation. We then compared projections of the species’ habitat suitability under climate change scenarios using species-level and lineage-level SDMs. In the Central Tropical Indo-Pacific region, both models predicted considerable range contraction in the future, but the lineage-level model predicted more severe habitat loss. The two modelling approaches predicted opposite pattern in habitat change in the Western Tropical Indo-Pacific region. Our results highlight the necessity of conserving distinct populations and genetic pools under climate change and have important implications for guiding future management of seagrasses.

Abstract Aim: To evaluate the respiratory functions of children with nephrotic syndrome (NS) by IOS and its correlation with spirometry. Methods: Fifty-five NS patients aged 3–18 years were included as the study group and 40 healthy children of the same age formed the control group. Patients were divided into nephrotic phase (first attack and relapse) and remission. Demographic, anthropometric and laboratory data of the children were recorded. Respiratory functions were evaluated by IOS and spirometry. Children over 6 years old performed both IOS and spirometry while children under 6 years performed only IOS. Results: The R (R5%, R10%, R5-20) and AX and Z5% values of IOS in patients with nephrotic phase were higher than remission patients and control group while spirometry indices of FEV1%, FEV1/FVC, PEF% and MEF25-75% were lower. FEV1% showed negative correlation with R5%, R10%, R15%, X10% and X15% results, FEV1/FVC% showed negative correlation with R5%, R5-20 and X15% results, FVC showed negative correlation with X10% results, MEF25-75% showed negative correlation with, R5%, R10%, R5-20, X15%, F res, Z5% and AX results. Conclusion: Our study demonstrated that respiratory functions measured by IOS and spirometry were affected at the time of nephrotic phase in NS patients. And IOS, a novel method easily applicable even in small children, is a valuable and reliable tool to detect this condition; given its good correlation with spirometry. Keywords Nephrotic syndrome, Respiratory functions, Spirometry, Impulse Oscillometry

S-ICD: Is it time for radiological follow-ups?

Allergic inflammation after allergen challenge – insights from the tissueTo the Editor,Limited data exist on the infiltration of eosinophils in direct response to allergen exposure in asthmatic patients. The experimental procedure of segmental allergen provocation (SAP) in mild asthmatic subjects is an extremely valuable study tool to investigate mechanisms of bronchial asthma in patients in general and in particular for the role of eosinophils. In this procedure, BAL and bronchial mucosa can be analysed simultaneously after the induction of allergic inflammation. Older studies yielded data on different time points after the challenge with contradictory results. Eosinophils were studied in mucosa and airway lumen of mild asthmatics undergoing segmental allergen provocation1,2. Here, eosinophils and their release products were investigated in thick sections of the bronchial biopsies. Subject data, methods and detailed results are given in the supplement. All subjects showed a clear eosinophilic response in the airway lumen and mucosa 24 hours after the challenge (Figure 1, S1). The data on neutrophils were inconclusive (Figure 1, S2). There was an increase of eosinophils in the mucosa and in the BAL. In the BAL the concentrations of IL‑5 and ECP were elevated (supplement). In the mucosa ECP stained areas were found elevated as well as signs of eosinophil activation and degranulation (Figure 2). ECP staining was associated with cellular structures, small granules or dispersed over a large area beneath the epithelium. The degree of released mediators into the tissue is an important parameter investigating new drugs for asthma. In the presented study not cell associated, free ECP positive granules were seen at baseline but only to a small extent. However, after allergen challenge the ECP volume was significantly increased and only few distinct cells could be detected being positive for ECP. These results suggest that in human tissue eosinophils degranulate to a significant amount after a single allergen challenge and therefore release all their toxic content into the surrounding tissue. This is in contrast to animal models of asthma where eosinophilic degranulation after allergen challenge does not occur extensively 3,4. In the present study, subjects with a strong IL-5 reaction in BAL showed a strong eosinophilic response in the lumen. However, BAL IL-5 levels did not correlate with eosinophil numbers in the mucosa or volume of ECP positive surfaces in the mucosa (Figure S3). It is a long known fact that IL-5 levels in the BAL correlate highly with absolute numbers of eosinophils in the same compartment 5. In the present study the allergic reaction is comparable to those of other studies. The missing correlation between IL-5 in the BAL and numbers of tissue eosinophils showed that the relationship between both compartments is not as simple as assumed. Here, the data for the volume of ECP positive surfaces may give an important hint. Interestingly, the volume of ECP positive surfaces was inversely correlated with TNF-α and IL-8. TNF-α enhances migration of eosinophils from mucosa to lumen shown in an in vitro cell culture model 6. Therefore, one possible explanation is the more TNF-α is found in the BAL the less activated eosinophils are found in the mucosa. In conclusion, the findings in subjects with mild asthma are in alignment with other published results and suggest that 1) human tissue eosinophils release their granules in non-provoked state, and 2) toxic content of these cells is significantly released into the surrounding tissue after a single allergen challenge whereas the distribution and the degree of activation and degranulation of eosinophils differs widely between subjects. Many eosinophils in the airways indicate many eosinophils in the mucosa. Three-dimensional analysis in thick tissue sections using confocal microscopy is a valuable tool in the investigation of bronchial biopsies from patients suffering from bronchial asthma.(Abbreviations: BAL=bronchoalveolar lavage, ECP=eosinophilic cation protein, IL=interleukin, MBP=major basic protein, NE=neutrophilic elastase, SAP=segmental allergen provocation, TNF=tumor necrosis factor)References1. Erpenbeck VJ, Hagenberg A, Dulkys Y, et al. Natural porcine surfactant augments airway inflammation after allergen challenge in patients with asthma. Am J Respir Crit Care Med.2004;169(5):578-586.2. Schaumann F, Muller M, Braun A, et al. Endotoxin augments myeloid dendritic cell influx into the airways in patients with allergic asthma.Am J Respir Crit Care Med. 2008;177(12):1307-1313.3. Denzler KL, Borchers MT, Crosby JR, et al. Extensive eosinophil degranulation and peroxidase-mediated oxidation of airway proteins do not occur in a mouse ovalbumin-challenge model of pulmonary inflammation. J Immunol. 2001;167(3):1672-1682.4. Malm-Erjefält M, Persson CG, Erjefält JS. Degranulation status of airway tissue eosinophils in mouse models of allergic airway inflammation. Am J Respir Cell Mol Biol. 2001;24(3):352-359.5. Sur S, Kita H, Gleich GJ, Chenier TC, Hunt LW. Eosinophil recruitment is associated with IL-5, but not with RANTES, twenty-four hours after allergen challenge. J Allergy Clin Immunol. 1996;97(6):1272-1278.6. Kikuchi I, Kikuchi S, Kobayashi T, et al. Eosinophil trans-basement membrane migration induced by interleukin-8 and neutrophils. Am J Respir Cell Mol Biol. 2006;34(6):760-765.Frauke Prenzler1, Thomas Tschernig2, Katherina Sewald1,5, Tibor Z Veres1,3, Susanne Rittinghausen1, Norbert Krug1,5, Jens M. Hohlfeld1,4,5, Armin Braun1,4,51Fraunhofer Institute for Toxicology and Experimental Medicine2Institute for Cell Biology and Anatomy, Saarland University, Homburg/Saar, Germany3Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA4 Institute of Immunology, Hannover Medical School, Hannover, Germany5 Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH) research network, Hannover, GermanyCorrespondence: Armin BraunPreclinical Pharmacology and ToxicologyFraunhofer Institute for Toxicology and Experimental Medicine (ITEM)Nikolai-Fuchs-Str. 1, 30625 Hannover, Germanyemail: armin.braun@item.fraunhofer.dePhone: +49(0)511/5350-263Acknowledgements: We would like to thank Isabelle Bleeker for processing the biopsy samples of the classical immunohistology.Funding: Supported by Deutsche Forschungsgemeinschaft (SFB587/ B8 und B4)Conflict of Interest: None of the authors has any financial interest.Contributions: AB, JH and NK planned and conducted the study. FP, AB and TT wrote the manuscript, all other authors read, corrected and approved the manuscript. TZV, KS, SR and FP established and performed the morphology and made the evaluation of tissue data.

Introduction The dissection of perirenal fat is of critical importance to kidney surgery and ease of dissection is more important when using minimally invasive approaches. This study aimed to determine the clinical, radiological, and pathological significance of adherent perirenal fat(APF). Materials and Methods This prospective study included 22 patients scheduled for partial nephrectomy and 40 patients for donor nephrectomy. Intra-operative fat dissection time was recorded and the complexity of perirenal fat dissection was surgeon-classified as easy, moderate, and difficult. Perirenal fat and subcutaneous fat thickness was measured. Measurement of perirenal fat depth, and the Hounsfield unit(HU) for both perirenal and subcutaneous fields was performed using CT images. All specimens were submitted for histopatological analysis. Researchers in each arm were blinded to other researchers’ data. Results Mean age of the patients was 51.3±12.7years. Mean perirenal fat dissection time was 15.0±13.5min. Patient demographics, BMI, nor occupational status differed between the 3 complexity of perirenal fat dissection groups. Radiological findings showed that there was a significant correlation between perirenal fat depth and complexity of perirenal fat dissection(p<0.05), but not with HU measurements or subcutaneous fat thickness. Surgeon classification of the complexity of perirenal fat dissection was in accordance with the duration of dissection(p<0.05). Perinephric fat contained more fibrous tissue in the patients with histologically proven APF than in those without(p<0.05). Conclusions APF is a challenge during kidney surgery. Difficult dissection prolongs the duration of surgery, which can lead to complications. Perirenal fat thickness measured via pre-operative CT might be used to predict APF.

Atrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments for AF are suboptimal as they are not targeting the molecular mechanisms underlying AF. In this regard, gene therapy is emerging as a promising approach for mechanism-based treatment of AF. In this review, we summarize recent advances and challenges in gene therapy for this important cardiovascular disease.

High power, short duration ablation: at least for the right pulmonary vein carina, maybe not so fastGustavo S. Guandalini, MD a and Francis E. Marchlinski, MD aa Section of Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia, PACorresponding author: Dr. Francis E. Marchlinski, Division of Cardiovascular Medicine, Electrophysiology Section, Hospital of the University of Pennsylvania, 3400 Spruce Street, 9 Founders Pavilion, Philadelphia, Pennsylvania 19104. E-mail: Francis.Marchlinski@pennmedicine.upenn.edu.The authors have no conflicts to disclose.Word count: 1,170.This research was supported by the Richard T and Angela Clark Innovation Fund in Cardiovascular Medicine.

This paper presents a damaging stress intensity function Kd for analyses of R-ratio effects on fatigue crack growth (FCG) in metals. The proposed formulation is based on the sum of strain and complementary energy and its role in FCG rate behavior in threshold and Paris region at R-ratios ranging from -2 to 0.97. It doesn’t invoke a crack closure assumption or fitting parameters for R<0.5-0.6. For a high R>0.7 it utilizes an experimentally determine correction factor, which accounts for excessive plastic dissipation in the monotonic plastic zone (MPZ).

Understanding the contributions of autotrophic respiration (Ra) and heterotrophic respiration (Rh) to total soil respiration (Rs) is necessary for accurate prediction of global carbon balance and net ecosystem production under environmental change. In this research, annual Rs and Rh and estimated were investigated by using a root trenching experiment in a Camphor tree (Cinnamomum camphora) forest in subtropical China for two years to qualify the relative contribution of Ra and Rh components to Rs, and to determine the environmental factors that control the seasonal changes in Ra, Rh and Rs. The results showed that annual mean Rs was 405 ± 219 gC m-2 year-1 in the studied forests, of which Rh and Ra were 240 ± 120 gC m-2 year-1 and 164 ±102 gC m-2 year-1, respectively. The contribution of Rh to Rs averaged 58.1%, ranging from 45 to 81%. The seasonal changes in Rs and Rh were highly correlated with soil temperature, but not to soil water content. Our results suggest microbial community and activity make a primary contribution to carbon flux released from soil to atmosphere in the studied forest ecosystems.

Kozyrev et al. report their results in a modified technique for coarctation of aorta with hypoplastic distal aortic arch (1). This paper represents a quality initiative as much as a technical manuscript. The authors included 32 patients during a three year time period from 2016 until 2019.