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Connexin 36 (Cx36) is responsible for signal transmission in electrical synapses by forming interneuronal gap junctions. Despite the critical role of Cx36 in normal brain function, the molecular architecture of the Cx36 gap junction channel (GJC) is unknown. Here, we determine cryo-electron microscopy structures of Cx36 GJC at 2.2-3.6 Å resolutions, revealing a dynamic equilibrium between its closed and open states. In the closed state, channel pores are obstructed by lipids, while N-terminal helices (NTHs) are excluded from the pore. In the open state with pore-lining NTHs, the pore is more acidic than those in Cx26 and Cx46/50 GJCs, explaining its strong cation selectivity. The conformational change during channel opening also includes the α-to-π-helix transition of the first transmembrane helix, which weakens the protomer-protomer interaction. Our structural analyses provide high resolution information on the conformational flexibility of Cx36 GJC and suggest a potential role of lipids in the channel gating.

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BACKGROUND: The poor performance of conventional techniques used in cardiovascular disease patients requiring hemodialysis or arterial bypass grafting has prompted tissue engineers to search for clinically appropriate off-the-shelf vascular grafts. Most patients with cardiovascular disease lack suitable autologous tissue because of age or previous surgery. Commercially available vascular grafts with diameters of < 5 mm often fail because of thrombosis and intimal hyperplasia. RESULT: Here, we tested tubular biodegradable poly-e-caprolactone/polydioxanone (PCL/PDO) electrospun vascular grafts in a rat model of aortic interposition for up to 12 weeks. The grafts demonstrated excellent patency (100%) confirmed by Doppler Ultrasound, resisted aneurysmal dilation and intimal hyperplasia, and yielded neoarteries largely free of foreign materials. At 12 weeks, the grafts resembled native arteries with confluent endothelium, synchronous pulsation, a contractile smooth muscle layer, and co-expression of various extracellular matrix components (elastin, collagen, and glycosaminoglycan). CONCLUSIONS: The structural and functional properties comparable to native vessels observed in the neoartery indicate their potential application as an alternative for the replacement of damaged small-diameter grafts. This synthetic off-the-shelf device may be suitable for patients without autologous vessels. However, for clinical application of these grafts, long-term studies (> 1.5 years) in large animals with a vasculature similar to humans are needed.

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During the coronavirus disease 2019 (COVID-19) pandemic, widened physical distance and social deprivation are being replaced with digital media use. The media's social function has tremendously increased following the COVID-19 era and adolescents living in a media-saturated world are the most vulnerable subjects of all. Social media use can encourage risky behavior in adolescents. Posting videos related to risk behaviors on social media has been linked to jeopardizing not only mental health but also physical safety. Herein, we report a case of a 12-year-old boy who intravenously self-injected Lactobacilli drinking yogurt for the purpose of filming a video to post on social media. He was treated with antibiotics based on Lactobacilli sepsis that cured him without any complications. In order to reduce the risk-taking behavior of adolescents, social norms need to be straightened up, and the social responsibility of hosts is strongly recommended.

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As adolescents started to be vaccinated against coronavirus disease 2019 (COVID-19), suspected myocarditis and pericarditis related to the vaccine were reported in adolescents. According to the Korea Disease Control and Prevention Agency (KDCA), 2,796,270 persons aged 12−18 years were fully vaccinated by December 8. Among these, 9223 adverse events were reported (0.33%). We aimed to elucidate the clinical courses and short-term outcomes for adolescents aged 12−18 with cardiac symptoms and suspected myo- or peri-carditis related to COVID-19 vaccination in South Korea. Methods: We retrospectively collected data on patients ≤ 18 years of age who had suspected myocarditis or pericarditis within 30 days of COVID-19 vaccination, from July 2021 to January 2022. Results: We reported on 40 adolescents in different South Korean provinces at two centers. Twenty-six cases (65%) were male, and the median age was 16 years (range, 13−18; IQR 14.5−17). Twenty-five cases (62.5%) occurred at the first dose, and fifteen (37.5%) occurred after the second dose. Symptoms started at a median of 2 days (range 0−29 days; IQR 1−5 days) after vaccination. The patients were treated with nonsteroidal anti-inflammatory drugs (77.5%), intravenous immunoglobulin (2.5%), glucocorticoids (20%), colchicine (5%), or no therapy (15%). Five patients (12.5%) required intensive care unit admission; one patient needed inotropic/vasoactive support. No patients required extracorporeal membrane oxygenation or died. The median hospital stay was one day (range 0−8 days; IQR 0−2 days). Twenty-one patients (52.5%) had an abnormal electrocardiogram; among these, seven patients had an elevated ST segment, six patients (15%) had decreased ejection fraction (<55%), and LV function was completely recovered in all of them. Conclusions: Most cases of suspected myocarditis after COVID-19 vaccination in adolescents ≤ 18 years had mild symptoms and clinical courses, as well as a complete recovery. Further studies are needed to evaluate long-term outcomes.

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BACKGROUND: We have designed a reinforced drug-loaded vascular graft composed of polycaprolactone (PCL) and polydioxanone (PDO) via a combination of electrospinning/3D printing approaches. To evaluate its potential for clinical application, we compared the in vivo blood compatibility and performance of PCL/PDO + 10%DY grafts doped with an antithrombotic drug (dipyridamole) with a commercial expanded polytetrafluoroethylene (e-PTFE) graft in a porcine model. METHODS: A total of 10 pigs (weight: 25-35 kg) were used in this study. We made a new 5-mm graft with PCL/PDO composite nanofiber via the electrospinning technique. We simultaneously implanted a commercially available e-PTFE graft (n = 5) and our PCL/PDO + 10%DY graft (n = 5) into the carotid arteries of the pigs. No anticoagulant/antiplatelet agent was administered during the follow-up period, and ultrasonography was performed weekly to confirm the patency of the two grafts in vivo. Four weeks later, we explanted and compared the performance of the two grafts by histological analysis and scanning electron microscopy (SEM). RESULTS: No complications, such as sweating on the graft or significant bleeding from the needle hole site, were seen in the PCL/PDO + 10%DY graft immediately after implantation. Serial ultrasonographic examination and immunohistochemical analysis demonstrated that PCL/PDO + 10%DY grafts showed normal physiological blood flow and minimal lumen reduction, and pulsed synchronously with the native artery at 4 weeks after implantation. However, all e-PTFE grafts occluded within the study period. The luminal surface of the PCL/PDO + 10%DY graft in the transitional zone was fully covered with endothelial cells as observed by SEM. CONCLUSION: The PCL/PDO + 10%DY graft was well tolerated, and no adverse tissue reaction was observed in porcine carotid models during the short-term follow-up. Colonization of the graft by host endothelial and smooth muscle cells coupled with substantial extracellular matrix production marked the regenerative capability. Thus, this material may be an ideal substitute for vascular reconstruction and bypass surgeries. Long-term observations will be necessary to determine the anti-thrombotic and remodeling potential of this device.

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Cardiopulmonary resuscitation (CPR) successfully restores systemic circulation approximately 50% of the time; however, many successfully restored patients have severe neurologic damage. In adults, the gray matter to white matter attenuation ratio (GWR) in brain computed tomography (CT) correlates with the neurologic outcome. However, in children, the clinical significance of GWR still remains unclear. The aim of this study was to evaluate the clinical characteristics of children who underwent CPR for cardiac arrest according to the survival and to demonstrate the differentiation of grey/white matter by Hounsfield units of brain CT and to characterize the attenuations of grey and white matters. METHODS: This is a retrospective single-center study. We enrolled those who underwent brain CT within 24 h after return of spontaneous circulation (ROSC) from January 2005 to June 2018. Brain CTs were taken within 24 h of ROSC. We measured the attenuation of grey and white matter in Hounsfield units and calculated GWR. They were compared with healthy controls. Patients were analyzed as follows: survivors vs. non-survivors and better neurologic outcome vs. worse neurologic outcome. RESULTS: Among 100 pediatric patients who had CPR, 56 met inclusion criteria. There were 24 patients who survived and 32 non-survivors. Our study revealed that the incidence of seizure, duration of CPR, and instances of hypothermia were significantly different between survivors and non-survivors. In both survivors and non-survivors, the attenuation of the caudate nucleus, putamen, GWR-basal ganglia, and average GWR were significantly different from controls. In regression analyses, the medial cortex and average GWR were the significant variables to predict survival, and the receiver operating curves revealed areas under curve of 0.733 and 0.666, respectively. Also, the medial cortex 1 was the only variable that predicted the neurologic outcome. CONCLUSIONS: There was some predictive survival value of GWR and medial cortex at the centrum semiovale level in early brain CT within 24 h after cardiac arrest. Although we could not find the predictive value of GWR in the neurologic outcome of pediatric patients, we found that the absolute attenuation of the medial cortex was low in patients with worse neurologic outcomes. Further prospective, multicenter studies are needed to determine the predictive value of GWR and the medial cortex.

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Although experimental extracorporeal membrane oxygenation (ECMO) animal models have been reported, there are few studies on the immune response to ECMO. We developed the venoarterial (VA) and venovenous (VV) model in rats and serially investigated the changes in the distribution of immune cells. Forty rats underwent both VA and VV modes of ECMO, and blood samples were collected at 1 day before ECMO (D-1), at the end of ECMO run (D+0), and 3 days after the ECMO (D+3). Flow cytometry was used to characterize surface marker expression (CD3, CD4, CD8, CD43, CD45, CD45R, CD161, and His48) on immune cells. Granulocytes were initially activated in both ECMO types and were further reduced but not normalized until 3 days of decannulation. Monocyte and natural killer cells were decreased initially in VA mode. B lymphocytes, helper T lymphocytes, and cytotoxic T lymphocytes also significantly decreased in VA modes after ECMO, but this phenomenon was not prominent in the VV modes. Overall immune cells proportion changed after ECMO run in both modes, and the immunologic balance altered significantly in the VA than in VV mode. Our ECMO model is feasible for the hemodynamic and immunologic research, and further long-term evaluation is needed.

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BACKGROUND: Current design strategies for small diameter vascular grafts (< 6 mm internal diameter; ID) are focused on mimicking native vascular tissue because the commercially available grafts still fail at small diameters, notably due to development of intimal hyperplasia and thrombosis. To overcome these challenges, various design approaches, material selection, and surface modification strategies have been employed to improve the patency of small-diameter grafts. REVIEW: The purpose of this review is to outline various considerations in the development of small-diameter vascular grafts, including material choice, surface modifications to enhance biocompatibility/endothelialization, and mechanical properties of the graft, that are currently being implanted. Additionally, we have taken into account the general vascular physiology, tissue engineering approaches, and collective achievements of the authors in this area. We reviewed both commercially available synthetic grafts (e-PTFE and PET), elastic polymers such as polyurethane and biodegradable and bioresorbable materials. We included naturally occurring materials by focusing on their potential application in the development of future vascular alternatives. CONCLUSION: Until now, there are few comprehensive reviews regarding considerations in the design of small-diameter vascular grafts in the literature. Here-in, we have discussed in-depth the various strategies employed to generate engineered vascular graft due to their high demand for vascular surgeries. While some TEVG design strategies have shown greater potential in contrast to autologous or synthetic ePTFE conduits, many are still hindered by high production cost which prevents their widespread adoption. Nonetheless, as tissue engineers continue to develop on their strategies and procedures for improved TEVGs, soon, a reliable engineered graft will be available in the market. Hence, we anticipate a viable TEVG with resorbable property, fabricated via electrospinning approach to hold a greater potential that can overcome the challenges observed in both autologous and allogenic grafts. This is because they can be mechanically tuned, incorporated/surface-functionalized with bioactive molecules and mass-manufactured in a reproducible manner. It is also found that most of the success in engineered vascular graft approaching commercialization is for large vessels rather than small-diameter grafts used as cardiovascular bypass grafts. Consequently, the field of vascular engineering is still available for future innovators that can take up the challenge to create a functional arterial substitute.

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Glioblastomas (GBMs) are the most aggressive type of primary brain tumors and provide a dismal prognosis. Thus far, several key genes have been identified in GBMs as prognostic and therapeutic targets. Mutations in two isocitrate dehydrogenase (IDH) genes, IDH1 and IDH2, commonly occur in low-grade gliomas and secondary high-grade gliomas, but are rare in primary GBMs. These mutations alter the catalytic activity of IDH proteins, promoting gliomagenesis. Gliomas with IDH1 or IDH2 mutation have better outcomes than do gliomas with wild-type IDH. The hot spots of IDH1 mutations (R132) and IDH2 mutations (R140 and R172) are well known and are considered as a possible biochemical explanation for the differing clinical characteristics of primary and secondary GBMs. We sought to find the incidence of IDH2 mutation and the characteristics of the gliomas with IDH2 mutation. Among 134 gliomas, which were operated in our hospital consecutively, we studied IDH1 and IDH2 mutations by Sanger sequencing and IDH2 mutation was identified in seven cases (5.2%, four oligodendrogliomas and three GBMs). IDH2 mutation was found in 3.3% of GBMs (3/90 cases) and 9.0% (4/44) of grades II to III gliomas. Here, we report the clinicopathological characteristics of the gliomas with IDH2 mutations including two cases of primary GBM carrying a novel missense IDH2 mutation (c. 484C>T, p. P162S).

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Total anomalous pulmonary venous return (TAPVR) is a rare and critical congenital vascular anomaly that requires an early operation. However, initial symptoms of TAPVR may be non-specific, and cardiovascular findings may be minimal. The heart may not be enlarged and there is often no cardiac murmur. Without cardiac murmur, these symptoms are similar to those of respiratory distress syndrome in newborns. Therefore, a high degree of suspicion and an early diagnosis of TAPVR are important. This condition generally occurs without a family history and has a low recurrence rate, but several familial cases, including siblings, have been reported worldwide. Additionally, several chromosomal or gene abnormalities associated with TAPVR have been reported. In the case presented here, two brothers with a 6-year age gap were diagnosed with TAPVR. Surgery was performed without cardiac or neurological complications. This is the first report on TAPVR in siblings in Korea.

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BRAF(V600E) mutations are involved in the development of melanoma, colon cancer, and papillary thyroid carcinoma. These mutations are also found in primary brain tumors at low to moderate frequencies. In this study, we investigated a series of brain tumors to determine the prevalence and associated clinicopathologic features of BRAF(V600E) mutations. By direct sequencing, we analyzed 223 brain tumors, including 51 gangliogliomas (GGs), 45 pilocytic astrocytomas (PAs), 12 pleomorphic xanthoastrocytomas (PXAs), 35 glioblastomas (GBs), 28 anaplastic astrocytomas (AAs), 44 oligodendroglial tumors (ODGs), 3 anaplastic oligoastrocytomas, and 5 diffuse astrocytomas. Thirty-six cases (16.1%) exhibited the BRAF(V600E) mutation, including 66.7% of PXAs, 23.5% of GGs, 15.6% of PAs, and 9.7% of the malignant gliomas; the latter included 14.3% of AAs, 8.6% of GBs, and 4.5% of ODGs. Copy number aberration at the 7q34 (BRAF) locus was found in 73.1% of PAs and 50% of PXAs. 9p Homozygous deletion was found in 66.7% of PXAs, but it was not correlated with the BRAF(V600E) mutation. Patients' age, sex, histologic grade, and progression-free survival were also not correlated with the BRAF(V600E) mutation. The BRAF(V600E) mutation in brain tumors did not have prognostic value but is certainly a diagnostic marker and therapeutic target, not only for pediatric low-grade gliomas but also for malignant gliomas, even though the rate of mutation was not high. These results should be verified in a larger study with more cases and a longer follow-up period to overcome the limitation of small sample size.

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To evaluate the involvement of translation initiation factors eIF4E and eIFiso4E in Chilli veinai mottle virus (ChiVMV) infection in pepper, we conducted a genetic analysis using a segregating population derived from a cross between Capsicum annuum 'Dempsey' containing an eIF4E mutation (pvr1(2)) and C. annuum 'Perennial' containing an eIFiso4E mutation (pvr6). C. annuum 'Dempsey' was susceptible and C. annuum 'Perennial' was resistant to ChiVMV. All F(1) plants showed resistance, and F(2) individuals segregated in a resistant-susceptible ratio of 166:21, indicating that many resistance loci were involved. Seventy-five F(2) and 329 F(3) plants of 17 families were genotyped with pvr1(2) and pvr6 allele-specific markers, and the genotype data were compared with observed resistance to viral infection. All plants containing homozygous genotypes of both pvr1(2) and pvr6 were resistant to ChiVMV, demonstrating that simultaneous mutations in eIF4E and eIFiso4E confer resistance to ChiVMV in pepper. Genotype analysis of F2 plants revealed that all plants containing homozygous genotypes of both pvr1(2) and pvr6 showed resistance to ChiVMV. In protein-protein interaction experiments, ChiVMV viral genome-linked protein (VPg) interacted with both eIF4E and eIFiso4E. Silencing of eIF4E and eIFiso4E in the VIGS experiment showed reduction in ChiVMV accumulation. These results demonstrated that ChiVMV can use both eIF4E and eIFiso4E for replication, making simultaneous mutations in eIF4E and eIFiso4E necessary to prevent ChiVMV infection in pepper.

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