Effects on Growth and Osteogenic Differentiation of Mesenchymal Stem Cells by the Zinc-Added Sol-Gel Bioactive Glass Granules

Responses of mesenchymal stem cells (MSCs) cultured with zinc-added (2 and 5%) bioactive glass granules were evaluated in terms of cell growth and osteogenic differentiation. MSCs were cultured with different quantities (3, 10 and 30) of glass granules for up to 21 days in the osteogenic medium. Cell growth was stimulated by a small quantity of glasses, particularly those that contained zinc. Osteogenic differentiation, as assessed by alkaline phosphatase activity (ALP) activity, was significantly enhanced by the glasses, particularly with large quantities of glass and for prolonged culturing. Expression of bone-sialo protein (BSP) was significantly up-regulated around the bioactive glass granules. Moreover, the zinc addition significantly altered the ALP and BSP depending on the culture time and glass quantity. Cellular mineralization was improved in all glass samples, and particularly in the 2% zinc-glass. Taken together, the zinc addition to bioactive glass induced the MSCs growth and their osteogenic differentiation, at least to the level of zinc-free glass, and with even higher level observed depending on the quantity and culture time. These findings indicate that the zinc addition to bioactive glass may be useful in development of biomaterials for the stimulation of adult stem cell in bone tissue engineering

Clinical outcomes in patients with persistent atrial fibrillation after technologic advances including contact force-guided and ablation index-guided ablation

We aimed to evaluate the influence of technological advances on ablation outcomes in patients with persistent atrial fibrillation (AF) (PeAF). Radiofrequency ablation for patients with AF has advanced, including contact force (CF)-sensing catheters and the ablation index (AI). Between 2009 and 2018, we analyzed 173 patients with PeAF who underwent catheter ablation. We categorized them into three groups: AF ablation without CF and AI information (no-CF group, n = 63), with CF without AI (CF-only group, n = 49), and with optimal AI-guided ablation (AI group, n = 61). Early (within 3months, ER) and late (from 3months to 1year, LR) AF recurrence after ablation was assessed. Procedure-related complications were also evaluated. The baseline characteristics were similar among the 3 groups, excluding the baseline antiarrhythmic drug history. Additional substrate modification after pulmonary vein isolation was significantly low in frequency in the AI group (71.4%, no-CF; 69.4%, CF-only; 41.0%, AI, p = 0.001). The AI group had a shorter mean procedure-related time than the other groups. Both ER and LR of PeAF showed a trend of reduction with technological advances. With a short experience (less than 1year), the CF-only group showed more ER and LR than that shown by the AI group. However, with a long experience (more than 1year), ER and LR occurred similarly in the two groups. Procedure-related complications improved with technological advances. As ablation technology advanced, favorable clinical outcomes with short procedural times were observed. However, prospective, large multicenter studies are needed to verify these results.This work was supported by the Korea Medical Device Development Fund grant funded by the Korean Government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 202013B14) and by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (Grant 2020R1F1A106740)

Impedance drop determines ablation lesion volume at the same level of ablation index

New parameters such as ablation index (AI) have been developed to create reliable ablation lesions. This study was performed to evaluate whether RF energy delivery with the same ablation index creates the similar ablation lesion volume. Ablation lesions were created in 5 pig hearts at ex-vivo state. Ablation was performed using an external-irrigation contact-force sensing catheter on the epicardial side of the left ventricle with 90-degree of angle. RF ablation time was adjusted for targeting AI 600 at 8 different conditions. Lesion volume created with 0–5g of contact force at 20 W was significantly lower than that of 11–20g at 40W despite of the same AI (125 ± 76.2 vs. 272 ± 49.5 mm3, P < 0.05). Quality of ablation lesion was variable in the condition of poor contact at low power for the ablation of ex-vivo swine left ventricle, and high-quality lesions could be expected when the impedance drop is satisfactory even though the same level of AI is applied during ablation

Inhibitory Synapses Are Repeatedly Assembled and Removed at Persistent Sites In Vivo

Older concepts of a hard-wired adult brain have been overturned in recent years by in vivo imaging studies revealing synaptic remodeling, now thought to mediate rearrangements in microcircuit connectivity. Using three-color labeling and spectrally resolved two-photon microscopy, we monitor in parallel the daily structural dynamics (assembly or removal) of excitatory and inhibitory postsynaptic sites on the same neurons in mouse visual cortex in vivo. We find that dynamic inhibitory synapses often disappear and reappear again in the same location. The starkest contrast between excitatory and inhibitory synapse dynamics is on dually innervated spines, where inhibitory synapses frequently recur while excitatory synapses are stable. Monocular deprivation, a model of sensory input-dependent plasticity, shortens inhibitory synapse lifetimes and lengthens intervals to recurrence, resulting in a new dynamic state with reduced inhibitory synaptic presence. Reversible structural dynamics indicate a fundamentally new role for inhibitory synaptic remodeling—flexible, input-specific modulation of stable excitatory connections.National Eye Institute (Grant RO1 EY017656 and RO1 EY011894)National Institutes of Health (U.S.) (P41EB015871-26A1, 4R44EB012415-02, and NSF CBET-0939511)Singapore-MIT AllianceSingapore-MIT Alliance for Research and Technology CenterRuth L. Kirschstein National Research Service Award (F31AG044061)National Institutes of Health (U.S.) (Pre-Doctoral Training Grant T32GM007287

Differentiation of the right versus left outflow tract ventricular arrhythmias using local activation time at the His bundle electrogram

Background Although multiple algorithms based on surface electrocardiographic criteria have been introduced to localize idiopathic ventricular arrhythmia (VA) origins from the outflow tract (OT), their diagnostic accuracy and clinical usefulness remain limited. We evaluated whether local activation time of the His bundle region could differentiate left and right ventricular OT VA origins in the early stage of electrophysiology study. Methods We studied 30 patients who underwent catheter ablation for OT VAs with a left bundle branch block pattern and inferior axis QRS morphology. The interval between the local V signal on the mapping catheter placed in the RVOT and His bundle region (V(RVOT)-V(HB) interval) and the interval from QRS complex onset to the local V signal on the His bundle region (QRS-V(HB) interval) were measured during VAs. Results The V(RVOT)-V(HB) and QRS-V(HB) intervals were significantly shorter in patients with LVOT VAs. The area under the curve (AUC) for the V(RVOT)-V(HB) interval by receiver operating characteristic analysis was 0.865. A cutoff value of ≤ 50 ms predicted an LVOT origin of VA with sensitivity, specificity, and positive and negative predictive values of 100%, 62.5%, 40%, and 100%, respectively. The QRS-V(HB) interval showed similar diagnostic accuracy (AUC, 0.840), and a cutoff value of ≤ 15 ms predicted an LVOT origin of VA with a sensitivity, specificity, and positive and negative predictive values of 100%, 70.8%, 45.2%, and 100%, respectively. Conclusion The V(RVOT)-V(HB) and QRS-V(HB) intervals could differentiate left from right OT origins of VA with high sensitivity and negative predictive values

Recurrent Syncope Triggered by Temporal Lobe Epilepsy: Ictal Bradycardia Syndrome

Ictal asystole is potentially lethal, and known to originate from the involvement of limbic autonomic regions. Appropriate treatment must include an antiepileptic drug and the implantation of a pacemaker. We report the case of a 54-year-old male with recurrent syncope secondary to ictal asystole triggered by temporal lobe epilepsy. This was confirmed by combined Holter and video-electroencephalogram monitoring

Pulmonary Artery Embolotherapy in a Patient with Type I Hepatopulmonary Syndrome after Liver Transplantation

Although liver transplantation (LT) is the only effective treatment option for hepatopulmonary syndrome (HPS), the post-LT morbidity and mortality have been high for patients with severe HPS. We performed post-LT embolotherapy in a 10-year-old boy who had severe type I HPS preoperatively, but he failed to recover early from his hypoxemic symptoms after an LT. Multiple embolizations were then successfully performed on the major branches that formed the abnormal vascular structures. After the embolotherapy, the patient had symptomatic improvement and he was discharged without complications

High-Throughput Mutation Profiling Identifies Frequent Somatic Mutations in Advanced Gastric Adenocarcinoma

Background: Gastric cancer is one of the leading cancer types in incidence and mortality, especially in Asia. In order to improve survival, identification of a catalogue of molecular alterations underlying gastric cancer is a critical step for developing and designing genome-directed therapies. Methodology/Principal Findings The Center for Cancer Genome Discovery (CCGD) at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection platform, termed OncoMap v4, interrogates 474 “hotspot” mutations in 41 genes that are relevant for cancer. We performed OncoMap v4 in formalin-fixed paraffin-embedded (FFPE) tissue specimens from 237 gastric adenocarcinomas. Using OncoMap v4, we found that 34 (14.4%) of 237 gastric cancer patients harbored mutations. Among mutations we screened, PIK3CA mutations were the most frequent (5.1%) followed by p53 (4.6%), APC (2.5%), STK11 (2.1%), CTNNB1 (1.7%), and CDKN2A (0.8%). Six samples harbored concomitant somatic mutations. Mutations of CTNNB1 were significantly more frequent in EBV-associated gastric carcinoma (P = 0.046). Our study led to the detection of potentially druggable mutations in gastric cancer which may guide novel therapies in subsets of gastric cancer patients. Conclusions/Significance: Using high throughput mutation screening platform, we identified that PIK3CA mutations were the most frequently observed target for gastric adenocarcinoma