Acute Dapagliflozin Administration Ameliorates Cardiac Surgery-Associated Acute Kidney Injury in a Rabbit Model.

BACKGROUND: Several studies have shown that sodium-glucose cotransporter-2 inhibitors have a renoprotective effect on acute kidney injury (AKI), but their effect on cardiac surgery-associated AKI is unknown.Methods and Results: AKI was induced in 25 rabbits without diabetes mellitus by cardiopulmonary bypass (CPB) for 2 h and they were divided into 5 groups: sham; dapagliflozin-treated sham; CPB; dapagliflozin-treated CPB; and furosemide-treated CPB (n=5 in each group). Dapagliflozin was administered via the femoral vein before initiating CPB. Kidney tissue and urine and blood samples were collected after the surgical procedure. There were no differences in the hemodynamic variables of each group. Dapagliflozin reduced serum creatinine and blood urea nitrogen concentrations, and increased overall urine output (all P<0.05). Hematoxylin and eosin staining showed that the tubular injury score was improved after dapagliflozin administration (P<0.01). Dapagliflozin administration mitigated reactive oxygen species and kidney injury molecule-1 as assessed by immunohistochemistry (both P<0.0001). Protein expression analysis showed improvement of inflammatory cytokines and apoptosis, and antioxidant enzyme expression was elevated (all P<0.05) through activation of the nuclear factor erythroid 2-related factor 2 pathway (P<0.01) by dapagliflozin. CONCLUSIONS: Acute intravenous administration of dapagliflozin protects against CPB-induced AKI. Dapagliflozin may have direct renoprotective effects in renal tubular cells.

Efficacy of Sac Coil Embolization in Endovascular Aortic Repair for Sac Shrinkage in Patients at a High Risk of Type II Endoleak from Lumbar Arteries.

BACKGROUND: In endovascular aortic repair (EVAR), preemptive embolization of sac branch vessels is effective in preventing postoperative type II endoleak (T2EL). However, this technique has not been widely adopted especially for lumbar arteries (LAs) because of technical difficulties and time constraints. This study aimed to investigate the efficacy of nonselective sac coil embolization, which is a simpler surgical method, in postoperative sac shrinkage for patients at a high risk of T2EL from LAs. METHODS: We retrospectively assessed 76 patients who underwent elective EVAR for abdominal aortic aneurysm with 4 or more patent LAs or at least 1 patent LA of ≥2 mm at our hospital between January 2014 and December 2022. The patients who underwent sac coil embolization were included in Group Ⅰ (n = 20), and the others were divided into 2 groups: those with an inferior mesenteric artery that was originally occluded or embolized by coils or stent graft bodies (Group Ⅱ, n = 21), and those without that (Group Ⅲ, n = 35). In Group Ⅰ, 0.035-inch coils were inserted into the sac after complete stent graft deployment. The cumulative incidence of sac shrinkage (≥5 mm) was compared between the groups. Further, univariable and multivariable Cox regression analyses were used to determine the predictors of sac shrinkage. RESULTS: Sac shrinkage (≥5 mm) was observed more frequently in Group Ⅰ (50%) than in Group Ⅱ (19%) and Group Ⅲ (17%) (P = 0.052 and 0.043, respectively). The cumulative incidence of sac shrinkage was significantly higher in Group Ⅰ than in Group Ⅱ (log-rank P = 0.039) and Group Ⅲ (log-rank P = 0.024). Multivariable Cox regression analyses revealed that sac embolization was a significant predictor of sac shrinkage (hazard ratio, 4.23; 95% confidence interval, 1.66-10.8; P = 0.003). CONCLUSIONS: Nonselective sac coil embolization in EVAR is potentially effective for sac shrinkage in the early postoperative phase in patients at high risk of T2EL from LAs. This simple procedure may improve prognosis after EVAR.

Modified del Nido cardioplegia is associated with low incidence of low main strong ion difference and hyperchloremia in pediatric patients after cardiac surgery.

PURPOSE: The aims of this study were (1) to determine the associations of cardioplegic solutions with postoperative main strong ion difference (mSID), which is the difference between sodium ion concentration and chloride ion concentration ([Cl-]) and (2) to determine the associations of cardioplegic solutions with markers of organ dysfunction. METHODS: In this retrospective cohort study, patients aged <5 years who underwent cardiac surgery in a tertiary teaching hospital were included. Patients were classified on the basis of the type of cardioplegic solution: modified del Nido cardioplegia (mDNC) and conventional cardioplegia (CC). The effects of mDNC on postoperative mSID and markers of organ functions were examined using propensity-matched analysis. RESULTS: A total of 500 cases were included. mDNC solution was used in 163 patients (32.6%). After propensity score matching, patients in the mDNC group (n = 152) had significantly higher minimum mSID [28 (26, 30) mEq/L vs. 27 (25, 29) mEq/L, p = 0.02] and lower maximum [Cl-] [112 (109, 114) mEq/L vs. 113 (111, 117) mEq/L, p < 0.001] than patients in the CC group (n = 304). The incidences of low mSID and hyperchloremia in the mDNC group were significantly lower than those in the CC group (63.8 vs. 75.7%, p = 0.01 and 63.2 vs. 79.3%, p < 0.001, respectively). There was no significant difference in the incidence of postoperative acute kidney injury and B-type natriuretic peptide level between the two groups. CONCLUSION: The use of modified del Nido cardioplegia may reduce the incidence of abnormal mSID and hyperchloremia compared with the use of a chloride-rich cardioplegic solution.

An Autopsy Case of Dextromethorphan Poisoning.

A woman in her 30s who was being treated for a mental illness with several psychotropic drugs was admitted to the hospital after being found in a state of unconsciousness and respiratory arrest at home. She was pronounced dead 12 hours after she was discovered. Her autopsy revealed symmetrical hemorrhagic necrosis in the putamen on both sides of her cerebrum. Although many drugs were detected in her blood, all of those other than dextromethorphan (DXM) were within or below the therapeutic range. Her blood DXM was 1.73 µg/ml at admission and 1.61 µg/ml at autopsy, which were within the toxic range or coma-to-death range. The cause of death was diagnosed as DXM poisoning. DXM can cause hallucinations and euphoria if taken in excess, but since it is available as an over-the-counter drug at general pharmacies, an increasing number of young people are overdosing on it, mistakenly believing it to be a safe drug with few side effects. We believe that further social measures against DXM are necessary in Japan, such as disseminating correct knowledge in society and regulating over-the-counter sales.

Thermal Embedding of Humicola insolens Cutinase: A Strategy for Improving Polyester Biodegradation in Seawater.

By thermal embedding of the commercially available enzyme Humicola insolens cutinase (HiC), this study successfully enhanced the biodegradability of various polyesters (PBS, PBSA, PCL, PBAT) in seawater, which otherwise show limited environmental degradability. Melt extrusion above the melting temperature was used for embedding HiC in the polyesters. The overall physical properties of the HiC-embedded films remained almost unchanged compared to those of the neat films. In the buffer, embedding HiC allowed rapid polymer degradation into water-soluble hydrolysis products. Biochemical oxygen demand tests showed that the HiC-embedded polyester films exhibited similar or much higher biodegradability than the biodegradable cellulose standard in natural seawater. Thermal embedding of HiC aims to accelerate the biodegradation of plastics that are already biodegradable but have limited environmental biodegradability, potentially reducing their contribution to environmental problems such as marine microplastics.

Outcomes associated with unrecognized acute kidney injury in postoperative pediatric cardiac patients.

BACKGROUND: The present retrospective study was carried out to determine the incidence of unrecognized cardiac surgery-associated acute kidney injury (CSA-AKI) due to infrequency of serum creatinine (SCr) measurements in pediatric cardiac patients and to assess the association between unrecognized CSA-AKI and clinical outcomes. METHODS: This study was a single-center, retrospective study of pediatric patients who underwent cardiac surgery. Patients were diagnosed with CSA-AKI based on SCr measurements, and unrecognized CSA-AKI was defined under the assumptions that there had been only one or two SCr measurements within 48 h after surgery: CSA-AKI unrecognized by one SCr measurement (AKI-URone), CSA-AKI unrecognized by two SCr measurements (AKI-URtwo), and CSA-AKI recognized by one and two SCr measurements (AKI-R). The change of SCr from baseline to postoperative day 30 (delta SCr30d) was assessed as a surrogate of kidney recovery. RESULTS: In a total of 557 cases, 313 patients (56.2%) were diagnosed with CSA-AKI, 188 (33.8%) of whom had unrecognized CSA-AKI. Delta SCr30d in the AKI-URtwo group and delta SCr30d in the AKI-URone group was not significantly different from delta SCr30d in the non-AKI group (p = 0.67 and p = 0.79, respectively). There were significant differences in the durations of mechanical ventilation, serum B-type natriuretic peptide levels, and lengths of stay in hospital between the non-AKI group and the AKI-URtwo group and between the non-AKI group and the AKI-URtwo group. CONCLUSIONS: Unrecognized CSA-AKI due to infrequent SCr measurements is not rare and is associated with prolonged mechanical ventilation, high postoperative BNP level, and prolonged length of stay in hospital. A higher resolution version of the Graphical abstract is available as Supplementary information.

Vigorous lateral export of the meltwater outflow from beneath an Antarctic ice shelf.

The instability and accelerated melting of the Antarctic Ice Sheet are among the foremost elements of contemporary global climate change. The increased freshwater output from Antarctica is important in determining sea level rise, the fate of Antarctic sea ice and its effect on the Earth's albedo, ongoing changes in global deep-ocean ventilation, and the evolution of Southern Ocean ecosystems and carbon cycling. A key uncertainty in assessing and predicting the impacts of Antarctic Ice Sheet melting concerns the vertical distribution of the exported meltwater. This is usually represented by climate-scale models as a near-surface freshwater input to the ocean, yet measurements around Antarctica reveal the meltwater to be concentrated at deeper levels. Here we use observations of the turbulent properties of the meltwater outflows from beneath a rapidly melting Antarctic ice shelf to identify the mechanism responsible for the depth of the meltwater. We show that the initial ascent of the meltwater outflow from the ice shelf cavity triggers a centrifugal overturning instability that grows by extracting kinetic energy from the lateral shear of the background oceanic flow. The instability promotes vigorous lateral export, rapid dilution by turbulent mixing, and finally settling of meltwater at depth. We use an idealized ocean circulation model to show that this mechanism is relevant to a broad spectrum of Antarctic ice shelves. Our findings demonstrate that the mechanism producing meltwater at depth is a dynamically robust feature of Antarctic melting that should be incorporated into climate-scale models.

Necrostatin-1 Attenuates Delayed Paraplegia after Transient Spinal Cord Ischemia in Rabbits by Inhibiting the Upregulation of Receptor-Interacting Protein Kinase 1 and 3.

BACKGROUND: Delayed-onset paraplegia is a disastrous complication after thoracoabdominal aortic open surgery and thoracic endovascular aortic repair. Studies have revealed that transient spinal cord ischemia caused by temporary occlusion of the aorta induces delayed motor neuron death owing to apoptosis and necroptosis. Recently, necrostatin-1 (Nec-1), a necroptosis inhibitor, has been reported to reduce cerebral and myocardial infarction in rats or pigs. In this study, we investigated the efficacy of Nec-1 in delayed paraplegia after transient spinal cord ischemia in rabbits and assessed the expression of necroptosis- and apoptosis-related proteins in motor neurons. METHODS: This study used rabbit transient spinal cord ischemia models using a balloon catheter. They were divided into a vehicle-treated group (n = 24), Nec-1-treated group (n = 24), and sham-controls (n = 6). In the Nec-1-treated group, 1 mg/kg of Nec-1 was intravascularly administered immediately before ischemia induction. Neurological function was assessed using the modified Tarlov score, and the spinal cord was removed 8 hr and 1, 2, and 7 days after reperfusion. Morphological changes were examined using hematoxylin and eosin staining. The expression levels of necroptosis-related proteins (receptor-interacting protein kinase [RIP] 1 and 3) and apoptosis-related proteins (Bax and caspase-8) were assessed using western blotting and histochemical analysis. We also performed double-fluorescence immunohistochemical studies of RIP1, RIP3, Bax, and caspase-8. RESULTS: Neurological function significantly improved in the Nec-1-treated group compared with that in the vehicle-treated group 7 days after reperfusion (median 3 and 0, P = 0.025). Motor neurons observed 7 days after reperfusion were significantly decreased in both groups compared with the sham group (vehicle-treated, P < 0.001; Nec-1-treated, P < 0.001). However, significantly more motor neurons survived in the Nec-1-treated group than in the vehicle-treated group (P < 0.001). Western blot analysis revealed RIP1, RIP3, Bax, and caspase-8 upregulation 8 hr after reperfusion in the vehicle-treated group (RIP1, P = 0.001; RIP3, P = 0.045; Bax, P = 0.042; caspase-8, P = 0.047). In the Nec-1-treated group, the upregulation of RIP1 and RIP3 was not observed at any time point, whereas that of Bax and caspase-8 was observed 8 hr after reperfusion (Bax, P = 0.029; caspase-8, P = 0.021). Immunohistochemical study revealed the immunoreactivity of these proteins in motor neurons. Double-fluorescence immunohistochemistry revealed the induction of RIP1 and RIP3, and that of Bax and caspase-8, in the same motor neurons. CONCLUSIONS: These data suggest that Nec-1 reduces delayed motor neuron death and attenuates delayed paraplegia after transient spinal cord ischemia in rabbits by selectively inhibiting necroptosis of motor neurons with minimal effect on their apoptosis.

A case of mediastinal abscess and infected aortic aneurysm caused by dissemination of Mycobacterium abscessus subsp. massiliense pulmonary disease.

An 81-year-old man was admitted to our hospital because of fever and malaise that had persisted for 3 months. The patient had undergone two aortic valve replacements, 10 and 5 years previously, because of aortic valve regurgitation and infectious endocarditis. He also had had asymptomatic Mycobacterium abscessus complex (MABC) pulmonary disease for the two previous years. Contrast-enhanced computed tomography showed a mediastinal abscess and an ascending aortic aneurysm. Mycobacterium abscessus subsp. massiliense was cultured from his blood, suggesting the aortic aneurysm was secondary to infection of an implanted device. After enlargement over only a few days, a leakage of contrast medium to the mediastinal abscess was found on computed tomography. The patient was diagnosed with rupture of an infectious aortic aneurysm, and emergency aortic replacement and drainage of the mediastinal abscess were successful. The patient was treated with several antibiotics, including meropenem, amikacin, and clarithromycin, and his general condition improved. Cultures from both the mediastinal abscess and a pericardial patch that was placed at the time of surgery 5 years previously revealed MABC. In our case, the infected aortic aneurysm most likely resulted from MABC pulmonary disease rather than from previous intraoperative contamination. This route of infection is rare. Physicians should be aware of the possibility of dissemination and subsequent infection of implants related to MABC pulmonary disease.

Associations of systemic oxygen consumption with age and body temperature under general anesthesia: retrospective cohort study.

BACKGROUND: Body temperature (BT) is thought to have associations with oxygen consumption (VO2). However, there have been few studies in which the association between systemic VO2 and BT in humans was investigated in a wide range of BTs. The aims of this study were 1) to determine the association between VO2 and age and 2) to determine the association between VO2 and BT. METHODS: This study was a retrospective study of patients who underwent surgery under general anesthesia at a tertiary teaching hospital. VO2 was measured by the Dräger Perseus A500 anesthesia workstation (Dräger Medical, Lubeck, Germany). The associations of VO2 with age and BT were examined using spline regression and multivariable regression analysis with a random effect. RESULTS: A total of 7,567 cases were included in this study. A linear spline with one knot shows that VO2 was reduced by 2.1 ml/kg/min with one year of age (p < 0.001) among patients less than 18 years of age and that there was no significant change in VO2 among patients 18 years of age or older (estimate: 0.014 ml/kg/min, p = 0.08). VO2 in all bands of BT < 36.0 °C was not significantly different from VO2 in BT > = 36 °C and < 36.5 °C. Multivariable linear regression analysis showed that compared with VO2 in BT > = 36 °C and < 36.5 °C as a reference, VO2 levels were significantly higher by 0.57 ml/kg/min in BT > = 36.5 °C and < 37 °C (p < 0.001), by 1.8 ml/kg/min in BT > = 37 °C and < 37.5 °C (p < 0.001), by 3.6 ml/kg/min in BT > = 37.5 °C and < 38 °C (p < 0.001), by 4.9 ml/kg/min in BT > = 38 °C and < 38.5 °C (p < 0.001), and by 5.7 ml/kg/min in BT > = 38.5 °C (p < 0.001). The associations between VO2 and BT were significantly different among categorized age groups (p = 0.03). CONCLUSIONS: VO2 increases in parallel with increase in body temperature in a hyperthermic state but remains constant in a hypothermic state. Neonates and infants, who have high VO2, may have a large systemic organ response in VO2 to change in BT.

An Assessment of the Practice of Neuromuscular Blockade and the Association Between Its Prophylactic Use and Outcomes Among Postoperative Pediatric Cardiac Patients.

OBJECTIVES: The authors investigated the management of neuromuscular blocking agents (NMBAs) for pediatric patients after cardiac surgery, and compared the outcomes of patients who received prophylactic NMBA (pNMBA) infusions and patients without pNMBA infusions. DESIGN: A retrospective cohort study. SETTING: At a tertiary teaching hospital. PARTICIPANTS: Patients younger than 18, with congenital heart disease, who underwent cardiac surgery. INTERVENTIONS: Commencement of NMBA infusion in the first 2 hours after surgery MEASUREMENTS AND MAIN RESULTS: The primary endpoint was a composite of one or more of the following major adverse events (MAEs) that occurred within 7 days after surgery: death from any cause, a circulatory collapse that needed cardiopulmonary resuscitation, and requirement for extracorporeal membrane oxygenation. The secondary endpoints included the total duration of mechanical ventilation for the first 30 days after surgery. A total of 566 patients were included in this study. The MAEs occurred in 13 patients (2.3%). An NMBA was commenced within 2 hours after surgery in 207 patients (36.6%). There were significant differences in the incidence of postoperative MAEs between the pNMBA group and the non-pNMBA group (5.3% v 0.6%; p < 0.001). In multivariate regression models, pNMBA infusion was not significantly associated with the incidence of MAEs (odds ratio: 1.79, 95% CI: 0.23-13.93, p = 0.58), but was significantly associated with prolonged mechanical ventilation by 3.85 days (p < 0.001). CONCLUSIONS: Postoperative prophylactic neuromuscular blockade after cardiac surgery can be associated with prolonged mechanical ventilation, but has no association with MAEs among pediatric patients with congenital heart disease.

Regional Cerebral Oxygen Saturation and Estimated Oxygen Extraction Ratio as Predictive Markers of Major Adverse Events in Infants with Congenital Heart Disease.

Regional cerebral oxygen saturation (ScO2) determined by near-infrared spectroscopy, monitoring both arterial and venous blood oxygenation of the brain, could reflect the balance between oxygen delivery and consumption. The aim of this study was to determine the predictabilities of ScO2 and estimated oxygen extraction ratio (eO2ER) with outcomes in infants with congenital heart disease (CHD). This study was a two-center, retrospective study of patients at 12 months of age or younger with CHD who underwent cardiac surgery. The primary outcome was a composite of one or more major adverse events (MAEs) after surgery: death from any cause, circulatory collapse that needed cardiopulmonary resuscitation, and requirement for extracorporeal membrane oxygenation. Based on the assumptions of arterial to venous blood ratio, eO2ER was calculated. A total of 647 cases were included in this study. MAEs occurred in 16 patients (2.5%). There were significant differences in post-bypass ScO2 [46.61 (40.90, 52.05) vs. 58.52 (51.52, 66.08), p < 0.001] and post-bypass eO2ER [0.66 (0.60, 0.78) vs. 0.52 (0.43, 0.61), p < 0.001] between patients with MAEs and patients without MAEs. Area under the receiver operating curve (AUROC) of post-bypass ScO2 was 0.818 (95% confidence interval: 0.747-0.889), AUROC of post-bypass eO2ER was 0.783 (0.697-0.870) and AUROC of post-bypass maximum serum lactate level was 0.635 (0.525-0.746). Both ScO2 and eO2ER, especially after weaning off bypass, are acceptable predictive markers for predicting MAEs after cardiac surgery in infants.(227 words).

In Situ Raman Analysis of Biofilm Exopolysaccharides Formed in Streptococcus mutans and Streptococcus sanguinis Commensal Cultures.

This study probed in vitro the mechanisms of competition/coexistence between Streptococcus sanguinis (known for being correlated with health in the oral cavity) and Streptococcus mutans (responsible for aciduric oral environment and formation of caries) by means of quantitative Raman spectroscopy and imaging. In situ Raman assessments of live bacterial culture/coculture focusing on biofilm exopolysaccharides supported the hypothesis that both species engaged in antagonistic interactions. Experiments of simultaneous colonization always resulted in coexistence, but they also revealed fundamental alterations of the biofilm with respect to their water-insoluble glucan structure. Raman spectra (collected at fixed time but different bacterial ratios) showed clear changes in chemical bonds in glucans, which pointed to an action by Streptococcus sanguinis to discontinue the impermeability of the biofilm constructed by Streptococcus mutans. The concurrent effects of glycosidic bond cleavage in water-insoluble α - 1,3-glucan and oxidation at various sites in glucans' molecular chains supported the hypothesis that secretion of oxygen radicals was the main "chemical weapon" used by Streptococcus sanguinis in coculture.

PMEL p.Leu18del dilutes coat color of Kumamoto sub-breed of Japanese Brown cattle.

BACKGROUND: Coat color is important for registration and maintenance of livestock. Standard coat color of Kumamoto sub-breed of Japanese Brown cattle is solid brown, but individuals with diluted coat color have been observed recently. In this study, we attempted to identify polymorphism(s) responsible for coat color dilution by whole genome analysis. RESULTS: One of the diluted cattle possessed 7302 exonic polymorphisms which could affect genes' function. Among them, 14 polymorphisms in 10 coat color-related genes were assumed to be specific for the diluted cattle. Subsequent genotyping with three diluted cattle and 74 standard cattle elucidated that PMEL p.Leu18del was the causative polymorphism for coat color dilution in this sub-breed. Individuals with del/del type of this polymorphism showed diluted coat color, but coat color of heterozygotes were intermediate with various dilution rates. CONCLUSIONS: Coat color dilution of Kumamoto sub-breed was caused by PMEL p.Leu18del. The causative del allele has been detected in several genetically distant cattle breeds, suggesting that PMEL p.Leu18del can be used as a DNA marker to control cattle coat color.

The two-component response regulator OrrA confers dehydration tolerance by regulating avaKa expression in the cyanobacterium Anabaena sp. strain PCC 7120.

The cyanobacterium Anabaena sp. strain PCC 7120 exhibits dehydration tolerance. The regulation of gene expression in response to dehydration is crucial for the acquisition of dehydration tolerance, but the molecular mechanisms underlying dehydration responses remain unknown. In this study, the functions of the response regulator OrrA in the regulation of salt and dehydration responses were investigated. Disruption of orrA abolished or diminished the induction of hundreds of genes in response to salt stress and dehydration. Thus, OrrA is a principal regulator of both stress responses. In particular, OrrA plays a crucial role in dehydration tolerance because an orrA disruptant completely lost the ability to regrow after dehydration. Moreover, in the OrrA regulon, avaKa encoding a protein of unknown function was revealed to be indispensable for dehydration tolerance. OrrA and AvaK are conserved among the terrestrial cyanobacteria, suggesting their conserved functions in dehydration tolerance in cyanobacteria.

Clinical significance of 123I-BMIPP washout rate in patients with uncertain chronic heart failure.

BACKGROUND: Recently, triglyceride deposit cardiomyovasculopathy (TGCV) with defective intracellular lipolysis was found to be a disease that causes heart failure. As a diagnostic criterion for TGCV, an Iodaine-123-ß-methyl iodophenyl-pentadecanoic acid washout rate (BMIPP WOR) of < 10% is used, but its clinical significance in patients with heart failure remains to be clarified. METHODS: In 62 hospitalized patients with chronic heart failure, 123I-BMIPP myocardial single-photon emission computed tomography (SPECT) was performed predischarge state. The prevalence of TGCV was investigated. Subsequently, follow-up was conducted for ≥ 90 days (mean: 724.6 ± 392.7 days), and the association between the BMIPP WOR and cardiac events was examined, establishing all-cause mortality and admission due to heart failure as endpoints. RESULTS: Of the 62 patients, the WOR was < 10% in 41 (66.1%). Of these, 26 (41.9%) were diagnosed with definite TGCV. Furthermore, cardiac events were noted in 12 patients (19.4%). Analysis with Cox proportional hazards models showed that the BMIPP WOR < 4.5% was a significant event-predicting factor [HR 4.29, 95% CI: 1.20-16.87; p = 0.0245]. On a Kaplan-Meier curve, the WOR was 4.5%; there was a significant difference in the incidence of events (p = 0.0298). CONCLUSION: In the predischarge state of heart failure, 123I-BMIPP myocardial SPECT was performed. In approximately 40% of the patients, a diagnosis of TGCV was made. The results suggested that the BMIPP WOR is useful for predicting the prognosis of chronic heart failure patients regardless of TGCV.

Comparative tRNA sequencing and RNA mass spectrometry for surveying tRNA modifications.

Chemical modifications of the nucleosides that comprise transfer RNAs are diverse. However, the structure, location and extent of modifications have been systematically charted in very few organisms. Here, we describe an approach in which rapid prediction of modified sites through reverse transcription-derived signatures in high-throughput transfer RNA-sequencing (tRNA-seq) data is coupled with identification of tRNA modifications through RNA mass spectrometry. Comparative tRNA-seq enabled prediction of several Vibrio cholerae modifications that are absent from Escherichia coli and also revealed the effects of various environmental conditions on V. cholerae tRNA modification. Through RNA mass spectrometric analyses, we showed that two of the V. cholerae-specific reverse transcription signatures reflected the presence of a new modification (acetylated acp3U (acacp3U)), while the other results from C-to-Ψ RNA editing, a process not described before. These findings demonstrate the utility of this approach for rapid surveillance of tRNA modification profiles and environmental control of tRNA modification.

Core-Peripheral Temperature Gradient and Skin Temperature as Predictors of Major Adverse Events Among Postoperative Pediatric Cardiac Patients.

OBJECTIVE: During episodes of low cardiac output, sympathetic neurohumoral responses with peripheral vasoconstriction result in an increase in the core-peripheral temperature gradient (CPTG). However, assessment of CPTG as a surrogate of low cardiac output and a predictor of outcomes in pediatric cardiac patients rarely has been performed. In this retrospective study, the authors assessed the prognostic abilities of CPTG, skin temperature, and serum lactate level for predicting clinical outcomes. DESIGN: A retrospective single-center study. SETTING: Referral high-volume pediatric center. PATIENTS: Patients younger than four months of age with congenital heart disease who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of one or more of the following major adverse events (MAEs) that occurred within seven days after surgery: death from any cause, cardiac arrest, emergency chest reopening, and requirement for extracorporeal membrane oxygenation. A total of 661 patients were included in the study. Univariate logistic regression analyses showed no significant difference in the odds for MAEs with CPTG at admission and at six hours after surgery and in the odds for MAEs with skin temperature at admission. On the other hand, the odds for MAEs increased significantly with increase in serum lactate level at admission (odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.26-1.87, p < 0.001) and at six hours after surgery (OR: 1.94, 95% CI: 1.50-2.51, p < 0.001). Areas under the receiver operating curve at admission for predicting MAEs were 0.531 for CPTG, 0.557 for skin temperature, and 0.713 for serum lactate. Multivariate logistic regression analysis showed neither CPTG nor skin temperature at any time point was significantly associated with MAEs. CONCLUSIONS: Both CPTG and skin temperature had low performance for prediction of MAEs in children after cardiac surgery. Either of those markers, especially at admission, should not be used as a single marker for assessing the condition of a patient.

The RNA degradosome promotes tRNA quality control through clearance of hypomodified tRNA.

The factors and mechanisms that govern tRNA stability in bacteria are not well understood. Here, we investigated the influence of posttranscriptional modification of bacterial tRNAs (tRNA modification) on tRNA stability. We focused on ThiI-generated 4-thiouridine (s4U), a modification found in bacterial and archaeal tRNAs. Comprehensive quantification of Vibrio cholerae tRNAs revealed that the abundance of some tRNAs is decreased in a ΔthiI strain in a stationary phase-specific manner. Multiple mechanisms, including rapid degradation of a subset of hypomodified tRNAs, account for the reduced abundance of tRNAs in the absence of thiI Through transposon insertion sequencing, we identified additional tRNA modifications that promote tRNA stability and bacterial viability. Genetic analysis of suppressor mutants as well as biochemical analyses revealed that rapid degradation of hypomodified tRNA is mediated by the RNA degradosome. Elongation factor Tu seems to compete with the RNA degradosome, protecting aminoacyl tRNAs from decay. Together, our observations describe a previously unrecognized bacterial tRNA quality control system in which hypomodification sensitizes tRNAs to decay mediated by the RNA degradosome.

Carboxyhemoglobin levels in children during extracorporeal membrane oxygenation support: a retrospective study.

INTRODUCTION: Hemolysis is a common complication of extracorporeal membrane oxygenation (ECMO). There are few data on whether carboxyhemoglobin (COHb), a potential marker of hemolysis, are elevated during ECMO support. METHODS: We conducted a single-center, retrospective study comparing peak COHb levels of children pre-, during, and post-ECMO from January 2017 to August 2020. RESULTS: There were 154 ECMO runs in 147 children (154 PICU admissions) included in the study. The median age was 3.5 (IQR 0.2, 39.2) months. Veno-arterial ECMO was the predominant mode: 146/154 (94.8%). Eighty-seven children (56.5%) underwent cardiac surgery. Peak COHb levels during ECMO were statistically significantly higher compared to pre ECMO (COHb 1.8% (IQR 1.4, 2.6) vs COHb 1.2% (IQR 0.7, 1.7), p < 0.001) and post ECMO (COHb 1.6% (IQR 1.3, 2.2), p = 0.009). Children with COHb ⩾2% were younger and had longer duration of ECMO support. Plasma hemoglobin weakly correlated with COHb level (r = 0.14; p = 0.04). CONCLUSIONS: Carboxyhemoglobin levels increased during ECMO support compared to the pre and post ECMO period. Younger age and longer ECMO duration were associated with COHb levels ⩾2%. Plasma hemoglobin weakly correlated with COHb level.