Monolithic silicon for high spatiotemporal translational photostimulation.

Electrode-based electrical stimulation underpins several clinical bioelectronic devices, including deep-brain stimulators1,2 and cardiac pacemakers3. However, leadless multisite stimulation is constrained by the technical difficulties and spatial-access limitations of electrode arrays. Optogenetics offers optically controlled random access with high spatiotemporal capabilities, but clinical translation poses challenges4-6. Here we show tunable spatiotemporal photostimulation of cardiac systems using a non-genetic platform based on semiconductor-enabled biomodulation interfaces. Through spatiotemporal profiling of photoelectrochemical currents, we assess the magnitude, precision, accuracy and resolution of photostimulation in four leadless silicon-based monolithic photoelectrochemical devices. We demonstrate the optoelectronic capabilities of the devices through optical overdrive pacing of cultured cardiomyocytes (CMs) targeting several regions and spatial extents, isolated rat hearts in a Langendorff apparatus, in vivo rat hearts in an ischaemia model and an in vivo mouse heart model with transthoracic optical pacing. We also perform the first, to our knowledge, optical override pacing and multisite pacing of a pig heart in vivo. Our systems are readily adaptable for minimally invasive clinical procedures using our custom endoscopic delivery device, with which we demonstrate closed-thoracic operations and endoscopic optical stimulation. Our results indicate the clinical potential of the leadless, lightweight and multisite photostimulation platform as a pacemaker in cardiac resynchronization therapy (CRT), in which lead-placement complications are common.

Lethal and mutagenic effects of different LET radiations on Bacillus subtilis spores.

New, useful microorganism resources have been generated by ionizing radiation breeding technology. However, the mutagenic effects of ionizing radiation on microorganisms have not been systematically clarified. For a deeper understanding and characterization of ionizing radiation-induced mutations in microorganisms, we investigated the lethal effects of seven different linear energy transfer (LET) radiations based on the survival fraction (SF) and whole-genome sequencing analysis of the mutagenic effects of a dose resulting in an SF of around 1% in Bacillus subtilis spores. Consequently, the lower LET radiations (gamma [surface LET: 0.2 keV/µm] and 4He2+ [24 keV/µm]) showed low lethality and high mutation frequency (MF), resulting in the major induction of single-base substitutions. Whereas higher LET radiations (12C5+ [156 keV/µm] and 12C6+ [179 keV/µm]) showed high lethality and low MF, resulting in the preferential induction of deletion mutations. In addition, 12C6+ (111) ion beams likely possess characteristics of both low- and high-LET radiations simultaneously. A decrease in the relative biological effectiveness and an evaluation of the inactivation cross section indicated that 20Ne8+ (468 keV/µm) and 40Ar13+ (2214 keV/µm) ion beams had overkill effects. In conclusion, in the mutation breeding of microorganisms, it should be possible to regulate the proportions, types, and frequencies of induced mutations by selecting an ionizing radiation of an appropriate LET in accordance with the intended purpose.

COVID-19-Induced Eosinophilic Lower Airway Inflammation in Those With Multiple COVID-19 Vaccinations.

A 29-year-old woman was admitted with a diagnosis of ischemic enteritis. She had a coronavirus disease 2019 (COVID-19) infection four weeks before this visit and continued to experience a cough. Four months before, she received the third COVID-19 vaccine. Chest computer tomography revealed scattered ground-glass opacities in both upper lobes. Based on abnormalities in chest imaging, eosinophilia, and a high level of fractional exhaled nitric oxide, she was diagnosed with eosinophilic lower airway inflammation due to COVID-19. Since the visit, the patient had an intermittent fever and no radiological improvement, so systemic corticosteroid treatment was initiated, and the symptoms and clinical findings improved. Clinicians should know the potential association between COVID-19 and eosinophilic lower airway inflammation, which may still occur despite multiple vaccinations.

Novel reinforcement of corrugated nanofiber tissue-engineered vascular graft to prevent aneurysm formation for arteriovenous shunts in an ovine model.

Objective: Many patients who require hemodialysis treatment will often require a prosthetic graft after multiple surgeries. However, the patency rate of grafts currently available commercially has not been satisfactory. Tissue engineering vascular grafts (TEVGs) are biodegradable scaffolds created to promote autologous cell proliferation and functional neotissue regeneration and, accordingly, have antithrombogenicity. Therefore, TEVGs can be an alternative prosthesis for small diameter grafts. However, owing to the limitations of the graft materials, most TEVGs are rigid and can easily kink when implanted in limited spaces, precluding future clinical application. Previously, we developed a novel corrugated nanofiber graft to prevent graft kinking. Reinforcement of these grafts to ensure their safety is required in a preclinical study. In the present study, three types of reinforcement were applied, and their effectiveness was examined using large animals. Methods: In the present study, three different reinforcements for the graft composed of corrugated poly-ε-caprolactone (PCL) blended with poly(L-lactide-co-ε-caprolactone) (PLCL) created with electrospinning were evaluated: 1) a polydioxanone suture, 2) a 2-0 polypropylene suture, 3) a polyethylene terephthalate/polyurethane (PET/PU) outer layer, and PCL/PLCL as the control. These different grafts were then implanted in a U-shape between the carotid artery and jugular vein in seven ovine models for a total of 14 grafts during a 3-month period. In evaluating the different reinforcements, the main factors considered were cell proliferation and a lack of graft dilation, which were evaluated using ultrasound examinations and histologic and mechanical analysis. Results: No kinking of the grafts occurred. Overall, re-endothelialization was observed in all the grafts at 3 months after surgery without graft rupture or calcification. The PCL/PLCL grafts and PCL/PLCL grafts with a polydioxanone suture showed high cell infiltration; however, they had become dilated 10 weeks after surgery. In contrast, the PCL/PLCL graft with the 2-0 suture and the PCL/PLCL graft covered with a PET/PU layer did not show any graft expansion. The PCL/PLCL graft covered with a PET/PU layer showed less cell infiltration than that of the PCL/PLCL graft. Conclusions: Reinforcement is required to create grafts that can withstand arterial pressure. Reinforcement with suture materials has the potential to maintain cell infiltration into the graft, which could improve the neotissue formation of the graft.

Location matters: Offset in tissue-engineered vascular graft implantation location affects wall shear stress in porcine models.

Objective: Although surgical simulation using computational fluid dynamics has advanced, little is known about the accuracy of cardiac surgical procedures after patient-specific design. We evaluated the effects of discrepancies in location for patient-specific simulation and actual implantation on hemodynamic performance of patient-specific tissue-engineered vascular grafts (TEVGs) in porcine models. Methods: Magnetic resonance angiography and 4-dimensional (4D) flow data were acquired in porcine models (n = 11) to create individualized TEVGs. Graft shapes were optimized and manufactured by electrospinning bioresorbable material onto a metal mandrel. TEVGs were implanted 1 or 3 months postimaging, and postoperative magnetic resonance angiography and 4D flow data were obtained and segmented. Displacement between intended and observed TEVG position was determined through center of mass analysis. Hemodynamic data were obtained from 4D flow analysis. Displacement and hemodynamic data were compared using linear regression. Results: Patient-specific TEVGs were displaced between 1 and 8 mm during implantation compared with their surgically simulated, intended locations. Greater offset between intended and observed position correlated with greater wall shear stress (WSS) in postoperative vasculature (P < .01). Grafts that were implanted closer to their intended locations showed decreased WSS. Conclusions: Patient-specific TEVGs are designed for precise locations to help optimize hemodynamic performance. However, if TEVGs were implanted far from their intended location, worse WSS was observed. This underscores the importance of not only patient-specific design but also precision-guided implantation to optimize hemodynamics in cardiac surgery and increase reproducibility of surgical simulation.

Coarctation of the aorta with total anomalous pulmonary venous connection: a case report.

Total anomalous pulmonary venous connection (TAPVC) and coarctation of the aorta (CoA) rarely occur together. In affected patients, blood is supplied to the lower body by saturated ductal flow. Preoperative echocardiography may not show an acceleration of flow at the isthmus (coarctation), and the oxygen saturation (SpO2) at the feet may be satisfactory. Consequently, the severity of CoA is often underestimated before performing surgery. A 6-day-old boy weighing 2.6 kg with a diagnosis of supracardiac TAPVC was referred for surgical correction of his anomaly. The atrial septal defect (ASD) was 6.7 mm in diameter. There was a large patent ductus arteriosus (PDA) without flow acceleration at the preductal entry into the descending aorta. Only the TAPVC repair was planned, but immediately following ligation of the large PDA, the blood pressure in the lower extremity dropped to around 30 mmHg. The ligation was removed. The reason for the blood pressure discrepancy between the upper and the lower body was not clear as there was no arterial line in the upper extremity and a 6.7-mm-diameter ASD can support sufficient blood flow to the lower body without the PDA. A suspected CoA was found and repaired, followed by the TAPVC repair. Caution is necessary when repairing a TAPVC and coexisting large PDA as the severity of the CoA can easily be underestimated due to nonsignificant flow acceleration.

Complete Genome Sequence of the Cesium-Accumulating Bacterium Rhodococcus qingshengii CS98, Isolated from Soil in Japan.

Rhodococcus qingshengii CS98 is a bacterium isolated from soil in Japan that shows strong cesium-accumulating ability. Here, we report the complete genome sequence of R. qingshengii (6.7 Mb), which may provide useful genetic information supporting its bioremediation features.

Risk Factors for Mid-Term Liver Disease After the Fontan Procedure.

The Fontan procedure is a palliative surgery performed for patients with complex congenital heart disease who exhibit functional single ventricular physiology. Although clinical outcomes of the Fontan procedure have improved in recent years and most patients who undergo the procedure reach adulthood, Fontan-associated liver disease (FALD) is a noncardiovascular complication that has become increasingly common; its risk factors remain unknown.A total of 95 patients who underwent the Fontan procedure and who were followed up for at least three years at Gunma Children's Medical Center and Kitasato University Hospital between 1996 and 2015 were retrospectively enrolled in this study.The mean age of the patients at the time of Fontan procedure was 2.3 ± 1.4 years. Overall, 21 patients (23.1%) experienced FALD. All Fontan procedures were performed with extracardiac total cavopulmonary connection using 16-mm expanded polytetrafluoroethylene grafts. The presence of systemic right ventricle, requirement of pulmonary vasodilator, application of a non-fenestrated Fontan procedure, and absence of fenestration flow at the time of follow-up catheter examination were identified as predictors of FALD using univariate analysis. All these factors, except the requirement of pulmonary vasodilator, remained significant predictors of FALD in multivariate logistic regression analysis.Patients with a systemic right ventricle who undergo the Fontan procedure are at a high risk of FALD in the mid-term. Creating fenestration at the time of Fontan and maintaining the fenestration flow may reduce the mid-term risk of FALD.

Suppression of IFN-γ Production in Murine Splenocytes by Histamine Receptor Antagonists.

Accumulating evidence suggests that histamine synthesis induced in several types of tumor tissues modulates tumor immunity. We found that a transient histamine synthesis was induced in CD11b⁺Gr-1⁺ splenocytes derived from BALB/c mice transplanted with a syngeneic colon carcinoma, CT-26, when they were co-cultured with CT-26 cells. Significant levels of IFN-γ were produced under this co-culture condition. We explored the modulatory roles of histamine on IFN-γ production and found that several histamine receptor antagonists, such as pyrilamine, diphenhydramine, JNJ7777120, and thioperamide, could significantly suppress IFN-γ production. However, suppression of IFN-γ production by these antagonists was also found when splenocytes were derived from the Hdc-/- BALB/c mice. Suppressive effects of these antagonists were found on IFN-γ production induced by concanavalin A or the combination of an anti-CD3 antibody and an anti-CD28 antibody in a histamine-independent manner. Murine splenocytes were found to express H1 and H2 receptors, but not H3 and H4 receptors. IFN-γ production in the Hh1r-/- splenocytes induced by the combination of an anti-CD3 antibody and an anti-CD28 antibody was significantly suppressed by these antagonists. These findings suggest that pyrilamine, diphenhydramine, JNJ7777120, and thioperamide can suppress IFN-γ production in activated splenocytes in a histamine-independent manner.

Markers of peripheral perfusion during high-flow regional cerebral perfusion for aortic arch repair.

OBJECTIVES: High-flow regional cerebral perfusion (HFRCP) provides cerebral and somatic oxygen delivery through collateral vessels during aortic arch repair in small children; however, optimal flow conditions during HFRCP have not been established. We sought to identify markers of peripheral perfusion during HFRCP. METHODS: Between 2009 and 2016, in total 20 consecutive pediatric patients undergoing aortic arch repair with HFRCP were enrolled in this prospective, observational study. Median age was 20 days (range, 6-116 days); median body weight was 2.77 kg (range, 1.8-4.98 kg). Oxygen delivery ratio (Do2R) was calculated as the oxygen delivery during HFRCP divided by the oxygen delivery before HFRCP. Regional oxygen saturations on the forehead and on the thigh (rSo2T) were monitored during HFRCP, and postoperative creatinine kinase and lactate concentrations were measured as postoperative outcomes. Multivariate analyses were performed to clarify the effectiveness of Do2R and rSo2T as markers of peripheral perfusion during HFRCP. RESULTS: No deaths or neurologic impairments occurred. Multivariate analysis showed that the lowest rSo2T (P = .005) and cardiopulmonary bypass time (P = .012) predicted postoperative creatinine kinase concentration. Do2R was the only factor to predict postoperative lactate concentration (P < .001). Receiver operating characteristic analysis showed that Do2R less than 0.66 predicted risk of high postoperative lactate concentration (>5.0 mmol/L), with area under the curve of 0.95. CONCLUSIONS: For aortic arch repair in small children, rSo2T and Do2R during HFRCP are useful markers for predicting peripheral perfusion. Maintaining higher Do2R during HFRCP minimizes postoperative increases in lactate and creatinine kinase concentrations.

Draft Genome Sequence of the Radioresistant Bacterium Deinococcus aerius TR0125, Isolated from the High Atmosphere above Japan.

Deinococcus aerius strain TR0125 is a bacterium isolated from the high atmosphere above Japan that shows strong resistance to desiccation, UV-C, and gamma radiation. Here, we report the draft genome sequence of D. aerius (4.5 Mb), which may provide useful genetic information supporting its biochemical features.

Transareolar Video-Assisted Approach to the Atrial Septal Defect and Tricuspid Valve.

Minimally invasive atrial septal defect closure and tricuspid annuloplasty in female patients are normally performed through a right submammary anterior minithoracotomy approach. However, when the aortic root is located higher, the direction of aortic cannulation becomes not ideal through the submammary incision. In such cases, transareolar approach is useful. Through this approach, aortic cannulation and tricuspid operation can be performed with endoscopic assistance, and ASD closure can be performed under direct vision.

Outcomes of patients who declined surgery for acute Stanford type A aortic dissection with patent false lumen of the ascending aorta.

OBJECTIVES: This study aimed to evaluate the outcomes of patients who did not undergo initial aortic surgery for acute Stanford type A aortic dissection with a patent false lumen of the ascending aorta. METHODS: Inpatient and outpatient records were retrospectively reviewed. RESULTS: We identified 195 patients with acute type A aortic dissection with a patent ascending false lumen between January 1998 and March 2016. Of these, 137 underwent aortic surgery, 16 died before surgery and 42 declined aortic surgery. The ages of the patients who underwent and those who declined aortic surgery were 60.0 ± 10.6 years and 72.3 ± 12.4 years, respectively. The mortality rate of those who underwent and those who declined aortic surgery was 15 and 62% at 30 days and 19% and 67 at 90 days, respectively ( P < 0.0001). In the 58 patients who did not undergo initial aortic surgery, the maximum aortic diameter was correlated with survival ( P = 0.0037). At follow-up (3.7 ± 4.5 years; range 0-16.4 years), survival at 1, 5 and 10 years in those who underwent and those who declined initial aortic surgery was 78, 68 and 49%, and 29, 24 and 12%, respectively ( P < 0.0001). CONCLUSIONS: In this study of patients with acute Stanford type A aortic dissection with a patent false lumen of the ascending aorta, the mortality of those who declined initial aortic surgery was 62% at 30 days and 67% at 90 days, respectively, and a smaller aortic diameter was significantly associated with better survival.

A novel mechanism of "metal gel-shift" by histidine-rich Ni2+-binding Hpn protein from Helicobacter pylori strain SS1.

Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) is a universally used method for determining approximate molecular weight (MW) in protein research. Migration of protein that does not correlate with formula MW, termed "gel shifting" appears to be common for histidine-rich proteins but not yet studied in detail. We investigated "gel shifting" in Ni2+-binding histidine-rich Hpn protein cloned from Helicobacter pylori strain SS1. Our data demonstrate two important factors determining "gel shifting" of Hpn, polyacrylamide-gel concentration and metal binding. Higher polyacrylamide-gel concentrations resulted in faster Hpn migration. Irrespective of polyacrylamide-gel concentration, preserved Hpn-Ni2+ complex migrated faster (3-4 kDa) than apo-Hpn, phenomenon termed "metal gel-shift" demonstrating an intimate link between Ni2+ binding and "gel shifting". To examine this discrepancy, eluted samples from corresponding spots on SDS-gel were analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). The MW of all samples was the same (6945.66±0.34 Da) and identical to formula MW with or without added mass of Ni2+. MALDI-TOF-MS of Ni2+-treated Hpn revealed that monomer bound up to six Ni2+ ions non-cooperatively, and equilibrium between protein-metal species was reliant on Ni2+ availability. This corroborates with gradually increased heterogeneity of apo-Hpn band followed by compact "metal-gel shift" band on SDS-PAGE. In view of presented data metal-binding and "metal-gel shift" models are discussed.

Epicardial Implantable Cardioverter-Defibrillator in a 2-Month-Old Infant.

We describe the implantation of an implantable cardioverter defibrillator (ICD) in a 2-month-old infant with frequent sustained ventricular tachycardia (VT) refractory to antiarrhythmic agents. An epicardial ICD shock coil lead and pacing leads were placed, as was a cumbersome device console that was stored in a pocket between the left external and internal oblique muscles. These methods were safe and feasible even for such a small infant, and possible adverse events were avoided.

Factors associated with a low initial cerebral oxygen saturation value in patients undergoing cardiac surgery.

Regional cerebral oximetry using near-infrared spectroscopy device, an INVOS 5100 C (Medtronic, Minneapolis, MN, USA), during cardiac surgery aims to avoid perioperative neurological impairment, especially during cardiopulmonary bypass. However, it is not uncommon to encounter critically low initial cerebral regional oxygen saturation or a low value unresponsive to intervention. Therefore, it is important to identify factors associated with low saturation value other than true cerebral hypoxia. We investigated the relationship between preoperative regional cerebral oxygen saturation and clinical variables during cardiac surgery. From January 2013 to May 2016, 462 patients underwent elective cardiac surgery. Patient's ≤12 years of age, with acute cerebral infarction, with previous intracranial hemorrhage or neurosurgery, with concomitant aortic surgery, and having off-pump coronary artery bypass surgery were excluded. The remaining 223 patients were monitored by intraoperative regional cerebral oximetry. Univariate analysis found that scalp-cortex distance, cerebrospinal fluid thickness, left ventricular ejection fraction, hemoglobin concentration, estimated glomerular filtration rate, and hemodialysis were significantly correlated with the initial regional oxygen saturation value. Multiple regression analysis revealed that scalp-cortex distance, left ventricular ejection fraction, hemoglobin, and hemodialysis remained as significant variables. A receiver operating characteristic analysis found that for a low initial regional oxygen saturation value of 40%, the thresholds of scalp-cortex distance, left ventricular ejection fraction, and hemoglobin concentration were 17.6 mm, 45.2%, and 7.5 g/dl, respectively. In conclusion, brain atrophy, poor left ventricular function, anemia, and hemodialysis were associated with low initial cerebral regional oxygen saturation values in adult cardiac surgery patients.

Occurrence of trans monounsaturated and polyunsaturated fatty acids in Colwellia psychrerythraea strain 34H.

Colwellia psychrerythraea strain 34H is an obligately psychrophilic bacterium that has been used as a model cold-adapted microorganism because of its psychrophilic growth profile, significant production of cold-active enzymes, and cryoprotectant extracellular polysaccharide substances. However, its fatty acid components, particularly trans unsaturated fatty acids and long-chain polyunsaturated fatty acids (LC-PUFAs), have not been fully investigated. In this study, we biochemically identified Δ9-trans hexadecenoic acid [16:1(9t)] and LC-PUFAs such as docosahexaenoic acid. These results are comparable with the fact that the strain 34H genome sequence includes pfa and cti genes that are responsible for the biosynthesis of LC-PUFAs and trans unsaturated fatty acids, respectively. Strain 34H cells grown under static conditions at 5 °C had higher levels of 16:1(9t) than those grown under shaken conditions, and this change was accompanied by an antiparallel decrease in the levels of Δ9-cis hexadecenoic acid [16:1(9c)], suggesting that the cis-to-trans isomerization reaction of 16:1(9c) is activated under static (microanaerobic) culture conditions, that is, the enzyme could be activated by the decreased dissolved oxygen concentration of cultures. On the other hand, the levels of LC-PUFAs were too low (less than 3% of the total), even for cells grown at 5 °C, to evaluate their cold-adaptive function in this bacterium.

Aortic regurgitation due to fibrous strand rupture in the fenestrated left coronary cusp of the tricuspid aortic valve.

Fenestration-related massive aortic regurgitation is rare. The underlying mechanism is reported to be rupture of the fenestrated fibrous strand, and most ruptured cords have been reported in the bicuspid valve or in the right coronary cusp of the tricuspid aortic valve. We encountered a rare case of acute aortic regurgitation due to fibrous strand rupture in the fenestrated left coronary cusp. Preoperative echocardiography detected left coronary cusp prolapse, and operative findings revealed rupture of a fibrous strand in the left coronary cusp. For cases such as this, preoperative echocardiography would be useful for appropriate diagnosis.