Circular-target-style bifocal zoom metalens.

Optical zoom plays an important role in realizing high-quality image magnification, especially in photography, telescopes, microscopes, etc. Compared to traditional bulky zoom lenses, the high versatility and flexibility of metalens design provide opportunities for modern electronic and photonic systems with demands for miniature and lightweight optical zoom. Here, we propose an ultra-thin, lightweight and compact bifocal zoom metalens, which consists of a conventional circular sub-aperture and a sparse annular sub-aperture with different focal lengths. The imaging resolutions of such single zoom metalens with 164 lp/mm and 117 lp/mm at magnifications of 1× and 2× have been numerically and experimentally demonstrated, respectively. Furthermore, clear zoom images of a dragonfly wing pattern have been also achieved using this zoom metalens, showing its distinctive aspect in biological imaging. Our results provide an approach for potential applications in integrated optical systems, miniaturized imaging devices, and wearable devices.

Adult granulosa cell tumour of the ovary incidentally discovered during caesarean section in a pregnant patient after IVF: a rare case and a review of the literature.

Adult granulosa cell tumours (AGCTs) of the ovary are very rare during pregnancy. To date, only five cases of ovarian AGCT in pregnancy have been reported in the literature and the patients all conceived spontaneously. We report a case of AGCT of the ovary that was incidentally discovered during a caesarean section in a patient undergoing In vitro fertilisation (IVF). To the authors' knowledge, this is the first case of AGCT incidentally discovered during caesarean section in a pregnant patient after IVF. A 44-year-old primigravida with 39 weeks gestation was admitted to our hospital due to premature rupture of membranes in May 2019. She was treated by in vitro fertilisation due to being an elderly mother and she was pregnant after the first cycle. She was indicated for caesarean section due to conceiving following in vitro fertilisation and being an elderly mother. She gave birth to a 3,000 g baby boy and his Apgar scores were 8/1'-9/5'. When examining the adnexa, the left ovary had a tumour with a size of 7 × 4 × 4 cm. Left oophorectomy was performed and specimen sent to for histopathology. The histopathological diagnosis was an AGCT of the ovary. A month later, the patient received chemotherapy with Carboplatin and Paclitaxel for four cycles. After 32 months of follow-up, no recurrence was detected. In conclusion, AGCTs of the ovary are very rare during pregnancy. Pre-operative diagnosis is difficult. Conservative surgery should be considered in women who wish to have children. Patients should receive adequate counselling and long-term follow-up to ensure the highest survival rates and early detection of recurrence.

Role of the Ubiquitin Ligase RNF149 in the Development of Rat Neonatal Gonocytes.

Male reproductive function depends on the formation of spermatogonial stem cells from their neonatal precursors, the gonocytes. Previously, we identified several UPS enzymes dynamically altered during gonocyte differentiation. The present work focuses on understanding the role of the RING finger protein 149 (RNF149), an E3 ligase that we found to be strongly expressed in gonocytes and downregulated in spermatogonia. The quantification of RNF149 mRNA from postnatal day (PND) 2 to 35 (puberty) in rat testis, brain, liver, kidney, and heart indicated that its highest levels are found in the testis. RNF149 knock-down in PND3 rat gonocytes was performed to better understand its role in gonocyte development. While a proliferative cocktail of PDGF-BB and 17ß-estradiol (P+E) increased both the expression levels of the cell proliferation marker PCNA and RNF149 in mock cells, the effects of P+E on both genes were reduced in cells treated with RNF149 siRNA, suggesting that RNF149 expression is regulated during gonocyte proliferation and that there might be a functional link between RNF149 and PCNA. To examine RNF149 subcellular localization, EGFP-tagged RNF149 vectors were constructed, after determining the rat testis RNF149 mRNA sequence. Surprisingly, two variant transcripts were expressed in rat tissues, predicting truncated proteins, one containing the PA and the other the RING functional domains. Transfection in mouse F9 embryonal carcinoma cells and C18-4 spermatogonial cell lines showed differential subcellular profiles of the two truncated proteins. Overall, the results of this study support a role for RNF149 in gonocyte proliferation and suggest its transcription to variant mRNAs resulting in two proteins with different functional domains. Future studies will examine the respective roles of these variant proteins in the cell lines and isolated gonocytes.

Divergent Conversion of Double Isocyanides with Alkenyl Bromide to Polysubstituted Pyrroles and 4-Imino-4,5-dihydropyrrolo[3,4-b]pyrrol-6(1H)-one Derivatives by Pd-Catalyzed Tandem Cyclization Reactions.

Herein a novel and concise approach to pyrrole skeletons via Pd-catalyzed tandem cyclization reactions is investigated. The substrates for the transformation could be readily prepared by phosphoric acid-catalyzed Ugi reactions with available starting materials. In this strategy, two isocyanides participate in sequential isocyanide insertion reactions, and the chemoselectivity of the products is regulated by the steric hindrance of the isocyanide. A plausible mechanism for the formation of the corresponding adducts is proposed.

The impact of the ClearRT™ upgrade on target motion tracking accuracy in Radixact® Synchrony® lung treatments.

Background: The objective was to investigate the change in segmentation error of Radixact® Synchrony® lung treatment after its kV imaging system was upgraded from Generation 1 to Generation 2 in the ClearRT™ installation. Materials and methods: Radixact® Lung Synchrony® plans were created for the Model 18023 Xsight® Lung Tracking "XLT" Phantom combined with different lung target inserts with densities of 0.280, 0.500, 0.943 and 1.093 g/cc. After Radixact® Synchrony® treatment delivery using the Generation 1 and Generation 2 kV systems according to each plan, the tracking performance of the two kV systems on each density insert was compared by calculating the root mean square (RMS) error (δRMS) between the Synchrony-predicted motion in the log file and the known phantom motion and by calculating δ95%, the maximum error within a 95% probability threshold. Results: The δRMS and δ95% of Radixact® Synchrony® treatment for Gen1 kV systems deteriorated as the density of the target insert decreased, from 1.673 ± 0.064 mm and 3.049 ± 0.089 mm, respectively, for the 1.093 g/cc insert to 8.355 ± 5.873 mm and 15.297 ± 10.470 mm, respectively, for the 0.280 g/cc insert. In contrast, no such trend was observed in the δRMS or δ95% of Synchrony® treatment using the Gen2 kV system. The δRMS and δ95%, respectively, fluctuated slightly from 1.586 to 1.687 mm and from 2.874 to 2.971 mm when different target inserts were tracked by the Gen2 kV system. Conclusion: With improved image contrast in kV radiographs, the Gen2 kV imaging system can enhance the ability to track targets accurately in Radixact® Lung Synchrony® treatment and reduce the segmentation error. Our study showed that lung targets with density values as low as 0.280 cc/g could be tracked correctly in Synchrony treatment with the Gen2 kV imaging system.

A novel combined enteroscopy and laparoscopy approach to prevent urethral complications in management of rectourethral fistula.

BACKGROUND: For the last 20 years, laparoscopy management of anorectal malformations (ARM) has been challenged due to the development of postoperative urethral diverticulum or injury caused by the imprecise transection of rectourethral fistulae, particularly rectobulbar fistulae situated deep in the pelvis. We have developed a combined approach of enteroscopy and laparoscopy for intraluminal incision of a rectourethral fistula. METHODS: We retrospectively reviewed 47 ARM patients who underwent surgical corrections using the combined approach between January 2019 and June 2020. Early postoperative and subsequent follow-up results were evaluated. RESULTS: The median follow-up period was 12 months. The average age at surgery was 3.18 ± 0.64 months. The mean operative time of a single-incision laparoscopic-assisted anorectoplasty (SILAARP) was 1.19 ± 0.29 h. The time for intraluminal incision of the fistula was shortened from 14 to 2 min. No patients underwent a conversion. The average postoperative hospital stay, time to full feeds and placement of an anal tube were 10 days, 1 day, and 5 days, respectively. No urethral diverticulum, urinary injury, wound infection, rectal retraction, anal stenosis or rectal prolapse was encountered in the cohort. CONCLUSIONS: The combined enteroscopy and laparoscopy approach offers precise management of rectourethral fistulae. It could effectively obviate urethral complications, eliminating the obstacles of laparoscopy application in the management of ARMs.

Combinatorial Treatment of Human Cardiac Engineered Tissues With Biomimetic Cues Induces Functional Maturation as Revealed by Optical Mapping of Action Potentials and Calcium Transients.

Although biomimetic stimuli, such as microgroove-induced alignment (µ), triiodothyronine (T3) induction, and electrical conditioning (EC), have been reported to promote maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), a systematic examination of their combinatorial effects on engineered cardiac tissue constructs and the underlying molecular pathways has not been reported. Herein, human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs) were used to generate a micro-patterned human ventricular cardiac anisotropic sheets (hvCAS) for studying the physiological effects of combinatorial treatments by a range of functional, calcium (Ca2+)-handling, and molecular analyses. High-resolution optical mapping showed that combined µ-T3-EC treatment of hvCAS increased the conduction velocity, anisotropic ratio, and proportion of mature quiescent-yet-excitable preparations by 2. 3-, 1. 8-, and 5-fold (>70%), respectively. Such electrophysiological changes could be attributed to an increase in inward sodium current density and a decrease in funny current densities, which is consistent with the observed up- and downregulated SCN1B and HCN2/4 transcripts, respectively. Furthermore, Ca2+-handling transcripts encoding for phospholamban (PLN) and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) were upregulated, and this led to faster upstroke and decay kinetics of Ca2+-transients. RNA-sequencing and pathway mapping of T3-EC-treated hvCAS revealed that the TGF-ß signaling was downregulated; the TGF-ß receptor agonist and antagonist TGF-ß1 and SB431542 partially reversed T3-EC induced quiescence and reduced spontaneous contractions, respectively. Taken together, we concluded that topographical cues alone primed cardiac tissue constructs for augmented electrophysiological and calcium handling by T3-EC. Not only do these studies improve our understanding of hPSC-CM biology, but the orchestration of these pro-maturational factors also improves the use of engineered cardiac tissues for in vitro drug screening and disease modeling.

Sarco/endoplasmic reticulum Ca2+-ATPase is a more effective calcium remover than sodium-calcium exchanger in human embryonic stem cell-derived cardiomyocytes.

Human pluripotent stem cell (hPSCs)-derived ventricular (V) cardiomyocytes (CMs) display immature Ca2+-handing properties with smaller transient amplitudes and slower kinetics due to such differences in crucial Ca2+-handling proteins as the poor sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump but robust Na+-Ca2+ exchanger (NCX) activities in human embryonic stem cell (ESC)-derived VCMs compared with adult. Despite their fundamental importance in excitation-contraction coupling, the relative contribution of SERCA and NCX to Ca2+-handling of hPSC-VCMs remains unexplored. We systematically altered the activities of SERCA and NCX in human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs) and their engineered microtissues, followed by examining the resultant phenotypic consequences. SERCA overexpression in hESC-VCMs shortened the decay of Ca2+ transient at low frequencies (0.5 Hz) without affecting the amplitude, SR Ca2+ content and Ca2+ baseline. Interestingly, short hairpin RNA-based NCX suppression did not prolong the transient decay, indicating a compensatory response for Ca2+ removal. Although hESC-VCMs and their derived microtissues exhibited negative frequency-transient/force responses, SERCA overexpression rendered them less negative at high frequencies (>2 Hz) by accelerating Ca2+ sequestration. We conclude that for hESC-VCMs and their microtissues, SERCA, rather than NCX, is the main Ca2+ remover during diastole; poor SERCA expression is the leading cause for immature negative-frequency/force responses, which can be partially reverted by forced expression. Combinatorial approach to mature calcium handling in hESC-VCMs may help shed further mechanistic insights.NEW & NOTEWORTHY In this study of human pluripotent stem cell-derived cardiomyocytes, we studied the role of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and Na+-Ca2+ exchanger (NCX) in Ca2+ handling. Our data support the notion that SERCA is more effective in cytosolic calcium removal than the NCX.

Modulation of chromatin remodeling proteins SMYD1 and SMARCD1 promotes contractile function of human pluripotent stem cell-derived ventricular cardiomyocyte in 3D-engineered cardiac tissues.

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have the ability of differentiating into functional cardiomyocytes (CMs) for cell replacement therapy, tissue engineering, drug discovery and toxicity screening. From a scale-free, co-expression network analysis of transcriptomic data that distinguished gene expression profiles of undifferentiated hESC, hESC-, fetal- and adult-ventricular(V) CM, two candidate chromatin remodeling proteins, SMYD1 and SMARCD1 were found to be differentially expressed. Using lentiviral transduction, SMYD1 and SMARCD1 were over-expressed and suppressed, respectively, in single hESC-VCMs as well as the 3D constructs Cardiac Micro Tissues (CMT) and Tissue Strips (CTS) to mirror the endogenous patterns, followed by dissection of their roles in controlling cardiac gene expression, contractility, Ca2+-handling, electrophysiological functions and in vitro maturation. Interestingly, compared to independent single transductions, simultaneous SMYD1 overexpression and SMARCD1 suppression in hESC-VCMs synergistically interacted to increase the contractile forces of CMTs and CTSs with up-regulated transcripts for cardiac contractile, Ca2+-handing, and ion channel proteins. Certain effects that were not detected at the single-cell level could be unleashed under 3D environments. The two chromatin remodelers SMYD1 and SMARCD1 play distinct roles in cardiac development and maturation, consistent with the notion that epigenetic priming requires triggering signals such as 3D environmental cues for pro-maturation effects.

A novel method for monitoring the constancy of beam path accuracy in CyberKnife.

The aim of current work was to present a novel evaluation procedure implemented for checking the constancy of beam path accuracy of a CyberKnife system based on ArcCHECK. A tailor-made Styrofoam with four implanted fiducial markers was adopted to enable the fiducial tracking during beam deliveries. A simple two-field plan and an isocentric plan were created for determining the density override of ArcCHECK in MultiPlan and the constancy of beam path accuracy respectively. Correlation curves for all diodes involved in the study were obtained by analyzing the dose distributions calculated by MultiPlan after introducing position shifts in anteroposterior, superoinferior, and left-right directions. The ability of detecting systematic position error was also evaluated by changing the position of alignment center intentionally. The one standard deviation (SD) result for reproducibility test showed the RMS of 0.054 mm and the maximum of 0.263 mm, which was comparable to the machine self-test result. The mean of absolute value of position errors in the constancy test was measured to 0.091 mm with a SD of 0.035 mm, while the root-mean-square was 0.127 mm with a SD of 0.034 mm. All introduced systematic position errors range from 0.3 to 2 mm were detected successfully. Efficient method for evaluating the constancy of beam path accuracy of CyberKnife has been developed and proven to be sensitive enough for detecting a systematic drift of robotic manipulator. Once the workflow is streamlined, our proposed method will be an effective and easy quality assurance procedure for medical physicists.

Development of a novel methodology for QA of respiratory-gated and VMAT beam delivery using Octavius 4D phantom.

The objective of this study was to develop and evaluate a series of quality assurance (QA) techniques based on Octavius 4D phantom for testing of respiratory-gated treatment delivery, integrity of dose rate vs gantry speed in volumetric-modulated arc therapy (VMAT) commissioning, and multileaf collimator (MLC) positioning accuracy of a linear accelerator. An Octavius 4D phantom capable of rotating with the gantry and recording the detector signal with a sampling rate of 10 Hz was isocentrally set up and an inclinometer was also installed to measure the gantry angle simultaneously. A simple arc test was created and delivered with gating function activated to measure the timing accuracy of the gating window. A tailor-made dose rate vs gantry speed plan was also designed to test the accuracy of measured dose rate, gantry speed, and actual control points. All experiments were conducted while machine log files were collected for comparison. The variations of beam flatness, symmetry, and field size were analyzed as a function of gantry angle to evaluate the influence from the modulation of dose rate and gantry speed. MLC position accuracy was evaluated based on specific garden fence plans. The time of gating window was measured to be less than 10-millisecond deviation from the log data. Gantry backlash was observed and quantified to be 1.72° with an extra stabilization time of 1.16 seconds for a gating arc with gantry speed of 6°/s. In the dose rate vs gantry speed test, the mean deviation between measured gantry angle and log data was less than 0.2° after a time delay of 0.25 second was corrected. The measured dose rate agreed with the log data very well with a mean deviation of 0.05%, and even the transit of modulation was tracked successfully. There was a statistically significant difference on the variation of beam parameters between a VMAT plan and a simple arc plan. The induced MLC position errors were detected with an accuracy of 0.05 mm. The leaf position reproducibility was found to be better than 0.02 mm, whereas the routine MLC position accuracy was better than 0.1 mm. A time-resolved method using Octavius 4D phantom has been developed and proven to be convenient for respiratory gating QA, dose rate vs gantry speed test, and MLC QA. Gating time, dose rate, and gantry speed-induced leave position error could be directly measured with high accuracy after comparison with the machine log data. This study also highlights the capability of the phantom in quantifying the variation of flatness, symmetry, and field size during gantry rotation.

Probing flecainide block of INa using human pluripotent stem cell-derived ventricular cardiomyocytes adapted to automated patch-clamping and 2D monolayers.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are emerging tools for applications such as drug discovery and screening for pro-arrhythmogenicity and cardiotoxicity as leading causes for drug attrition. Understanding the electrophysiology (EP) of hPSC-CMs is essential but conventional manual patch-clamping is highly laborious and low-throughput. Here we adapted hPSC-CMs derived from two human embryonic stem cell (hESC) lines, HES2 and H7, for a 16-channel automated planar-recording approach for single-cell EP characterization. Automated current- and voltage-clamping, with an overall success rate of 55.0 ±â€¯11.3%, indicated that 90% of hPSC-CMs displayed ventricular-like action potential (AP) and the ventricular cardiomyocytes (VCMs) derived from the two hESC lines expressed similar levels of INa, ICaL, Ikr and If and similarly lacked Ito and IK1. These well-characterized hPSC-VCMs could also be readily adapted for automated assays of pro-arrhythmic drug screening. As an example, we showed that flecainide (FLE) induced INa blockade, leftward steady-state inactivation shift, slowed recovery from inactivation in our hPSC-VCMs. Since single-cell EP assay is insufficient to predict drug-induced reentrant arrhythmias, hPSC-VCMs were further reassembled into 2D human ventricular cardiac monolayers (hvCMLs) for multi-cellular electrophysiological assessments. Indeed, FLE significantly slowed the conduction velocity while causing AP prolongation. Our RNA-seq data suggested that cell-cell interaction enhanced the maturity of hPSC-VCMs. Taken collectively, a combinatorial approach using single-cell EP and hvCMLs is needed to comprehensively assess drug-induced arrhythmogenicity.

Functional and transcriptomic insights into pathogenesis of R9C phospholamban mutation using human induced pluripotent stem cell-derived cardiomyocytes.

Dilated cardiomyopathy (DCM) can be caused by mutations in the cardiac protein phospholamban (PLN). We used CRISPR/Cas9 to insert the R9C PLN mutation at its endogenous locus into a human induced pluripotent stem cell (hiPSC) line from an individual with no cardiovascular disease. R9C PLN hiPSC-CMs display a blunted ß-agonist response and defective calcium handling. In 3D human engineered cardiac tissues (hECTs), a blunted lusitropic response to ß-adrenergic stimulation was observed with R9C PLN. hiPSC-CMs harboring the R9C PLN mutation showed activation of a hypertrophic phenotype, as evidenced by expression of hypertrophic markers and increased cell size and capacitance of cardiomyocytes. RNA-seq suggests that R9C PLN results in an altered metabolic state and profibrotic signaling, which was confirmed by gene expression analysis and picrosirius staining of R9C PLN hECTs. The expression of several miRNAs involved in fibrosis, hypertrophy, and cardiac metabolism were also perturbed in R9C PLN hiPSC-CMs. This study contributes to better understanding of the pathogenic mechanisms of the hereditary R9C PLN mutation in the context of human cardiomyocytes.

High-Content Electrophysiological Analysis of Human Pluripotent Stem Cell-Derived Cardiomyocytes (hPSC-CMs).

Considerable interest has been raised to develop human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as a model for drug discovery and cardiotoxicity screening. High-content electrophysiological analysis of currents generated by transmembrane cell surface ion channels has been pursued to complement such emerging applications. Here we describe practical procedures and considerations for accomplishing successful assays of hPSC-CMs using an automated planar patch-clamp system.

Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells.

A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes (DLG2, KCNE4, PTRF, HTR2C, CAMKV) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions.

Increasing the physical size and nucleation status of human pluripotent stem cell-derived ventricular cardiomyocytes by cell fusion.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) provide an unlimited source of donor cells for potential cardiac regenerative therapies. However, hPSC-CMs are immature. For instance, hPSC-CMs are only 1/10 of the physical size of their adult counterparts; the majority are mono- rather than bi- or multi-nucleated, which is an evolutionary adaptive feature in metabolically active cells such as adult CMs. Here, we attempted to increase the physical size and nucleation status of hPSC-derived ventricular (V) cardiomyocytes (hPSC-VCMs) using chemically-induced cell fusion, and examined the subsequent functional effects. Polyethylene glycol (PEG) was employed to fuse a 1:1 mixture of lentiviral vectors LV-MLC2v-GFP- or -tdTomato-labeled hPSC-VCMs, such that hPSC-VCMs fused syncytia (FS) were identified as doubly GFP+/tdTomato+ multi-nucleated cells. These microscopically-identified FS were doubled in size as gauged by their capacitance when compared to the control mononucleated hPSC-VCMs using patch-clamp analysis. Reduced automaticity or action potential (AP) firing rate and moderately prolonged AP duration were observed in FS from day 6 post-fusion induction. However, Ca2+ handling, mitochondrial biogenesis and the extent of apoptosis were not significantly altered. We conclude that larger, multi-nucleated hPSC-VCMs FS can be created by chemically-induced cell fusion but global maturation requires additional triggering cues.

A Micropatterned Human Pluripotent Stem Cell-Based Ventricular Cardiac Anisotropic Sheet for Visualizing Drug-Induced Arrhythmogenicity.

A novel cardiomimetic biohybrid material, termed as the human ventricular cardiac anisotropic sheet (hvCAS) is reported. Well-characterized human pluripotent stem-cell-derived ventricular cardiomyocytes are strategically aligned to reproduce key electrophysiological features of native human ventricle, which, along with specific selection criteria, allows for a direct visualization of arrhythmic spiral re-entry and represents a revolutionary tool to assess preclinical drug-induced arrhythmogenicity.

Non-cell autonomous cues for enhanced functionality of human embryonic stem cell-derived cardiomyocytes via maturation of sarcolemmal and mitochondrial KATP channels.

Human embryonic stem cells (hESCs) is a potential unlimited ex vivo source of ventricular (V) cardiomyocytes (CMs), but hESC-VCMs and their engineered tissues display immature traits. In adult VCMs, sarcolemmal (sarc) and mitochondrial (mito) ATP-sensitive potassium (KATP) channels play crucial roles in excitability and cardioprotection. In this study, we aim to investigate the biological roles and use of sarcKATP and mitoKATP in hESC-VCM. We showed that SarcIK, ATP in single hESC-VCMs was dormant under baseline conditions, but became markedly activated by cyanide (CN) or the known opener P1075 with a current density that was ~8-fold smaller than adult; These effects were reversible upon washout or the addition of GLI or HMR1098. Interestingly, sarcIK, ATP displayed a ~3-fold increase after treatment with hypoxia (5% O2). MitoIK, ATP was absent in hESC-VCMs. However, the thyroid hormone T3 up-regulated mitoIK, ATP, conferring diazoxide protective effect on T3-treated hESC-VCMs. When assessed using a multi-cellular engineered 3D ventricular cardiac micro-tissue (hvCMT) system, T3 substantially enhanced the developed tension by 3-folds. Diazoxide also attenuated the decrease in contractility induced by simulated ischemia (1% O2). We conclude that hypoxia and T3 enhance the functionality of hESC-VCMs and their engineered tissues by selectively acting on sarc and mitoIK, ATP.

Long-term outcome in patients receiving permanent pacemaker implantation for atrioventricular block: Comparison of VDD and DDD pacing.

A permanent pacemaker (PPM) with dual chamber pacing (DDD) offers atrioventricular synchronization for patients with atrioventricular block (AVB). Single lead atrial synchronous ventricular pacing mode (VDD) is an alternative, but there are concerns about its efficacy and risk of atrial undersensing. Whether VDD can be a good alternative in patients with AVB remains unknown. The aim of the present study was to compare the long-term risk of mortality of VDD with DDD pacing.A total of 207 patients undergoing PPM implantations for AVB with VDD mode were enrolled from 2000 to 2013. Another 828 age- and sex-matched patients undergoing DDD implantations during the same period of time were selected as the control group in a 1 to 4 ratio. The study endpoint was mortality.A total of 1035 patients (64.3% male) were followed up for 46.5 ±â€Š43.2 months. The mean ages were 75.0 years for VDD, and 74.9 years for DDD. The Kaplan-Meier survival analysis showed no significant difference in long-term survival between the VDD and DDD groups (log-rank P = 0.313). After adjustment for baseline characteristics, the VDD and DDD groups had a similar long-term prognosis with an adjusted hazard ratio of 0.875 (P = 0.445). Further analyses for the risk of cardiovascular and noncardiovascular deaths also showed no significant differences between the 2 groups.The long-term prognosis of VDD mode is comparable to that of DDD mode. Single lead VDD can be considered as an alternative choice in patients with AVB without sinus nodal dysfunction.

Acute augmentation for interstitial insufficiency of the posterior cruciate ligament. A two to five year clinical and radiographic study.

BACKGROUND: there is need to ascertain clinical and imaging outcomes after posterior cruciate ligament (PCL) augmentation. METHODS: we performed a retrospective analysis of clinical, imaging and functional data on 21 physically active males who underwent arthroscopic trans-tibial augmentation of the PCL for symptomatic grade III PCL insufficiency. The average follow-up time was 50 months (24-60 months). The Lysholm knee score was administered to all the patients, ligament laxity was evaluated with the posterior drawer test, the KT-1000 arthrometer, and the anteromedial tibial step-off. Standing antero-posterior, lateral and Merchant's view radiographs were taken preoperatively and at annual follow-up. RESULTS: post-operatively, ligament laxity and Lysholm knee scores were significantly improved than at baseline. Sixteen patients (73%) returned to pre-injury sport activity level, 3 patients (14%) returned to a lower level, 2 had to stop. We found radiographic degenerative changes in 5 of 22 affected knees (23%), with evidence of a statistically significant association between the occurrence of degenerative changes and the interval time from injury to surgery and duration of the follow up. CONCLUSIONS: arthroscopic transtibial single bundle autograft hamstring augmentation significantly improves the function of the knee, with an overall satisfactory outcome of 82% at 2-5 years from surgery.