Disfunction of dorsal raphe nucleus-hippocampus serotonergic-HTR3 transmission results in anxiety phenotype of Neuroplastin 65-deficient mice.

Anxiety disorders are the most common psychiatric condition, but the etiology of anxiety disorders remains largely unclear. Our previous studies have shown that neuroplastin 65 deficiency (NP65-/-) mice exhibit abnormal social and mental behaviors and decreased expression of tryptophan hydroxylase 2 (TPH2) protein. However, whether a causal relationship between TPH2 reduction and anxiety disorders exists needs to be determined. In present study, we found that replenishment of TPH2 in dorsal raphe nucleus (DRN) enhanced 5-HT level in the hippocampus and alleviated anxiety-like behaviors. In addition, injection of AAV-NP65 in DRN significantly increased TPH2 expression in DRN and hippocampus, and reduced anxiety-like behaviors. Acute administration of exogenous 5-HT or HTR3 agonist SR57227A in hippocampus mitigated anxiety-like behaviors in NP65-/- mice. Moreover, replenishment of TPH2 in DRN partly repaired the impairment of long-term potentiation (LTP) maintenance in hippocampus of NP65-/- mice. Finally, we found that loss of NP65 lowered transcription factors Lmx1b expression in postnatal stage and replenishment of NP65 in DRN reversed the decrease in Lmx1b expression of NP65-/- mice. Together, our findings reveal that NP65 deficiency induces anxiety phenotype by downregulating DRN-hippocampus serotonergic-HTR3 transmission. These studies provide a novel and insightful view about NP65 function, suggesting an attractive potential target for treatment of anxiety disorders.

NiH-Catalyzed Regio- and Enantioselective Hydroalkylation for the Synthesis of ß- or γ-Branched Chiral Aromatic N-Heterocycles.

A nickel hydride-catalyzed regio- and enantioselective hydroalkylation reaction was developed to give access to a library of chiral ß- or γ-branched aromatic N-heterocycles. This intriguing asymmetric transformation features excellent selectivities, step- and atom-economies, and generating two kinds of chiral products through one synthetic strategy. Furthermore, the possible reaction mechanism was extensively investigated using numerous control experiments and density functional theory calculations.

Catalytic Asymmetric Polycyclization of Tertiary Enamides with Silyl Enol Ethers: Total Synthesis of (-)-Cephalocyclidin A.

A catalytic enantioselective polycyclization of tertiary enamides with terminal silyl enol ethers has been developed by virtue of Cu(OTf)2 catalysis with a novel spiropyrroline-derived oxazole (SPDO) ligand. This tandem reaction offers an effective approach to assemble bicyclic and tricyclic N-heterocycles bearing both aza- and oxa-quaternary stereogenic centers, which are primal subunits in a range of natural alkaloids. Strategic application of this methodology and a late-stage radical cyclization as key steps have been showcased in the concise total synthesis of (-)-cephalocyclidin A.

1.9†µJ external-cavity dumped ultra-broad-area semiconductor nanosecond laser.

An external-cavity dumped nanosecond (ns) ultra-broad-area laser diode (UBALD) at around 966 nm with high pulse energy is demonstrated. A 1 mm UBALD is used to produce high output power and high pulse energy. A Pockels cell (PC) combines with two polarization beam splitters (PBSs) and is employed to cavity-dump a UBALD operating at 10 kHz repetition rate. At a pump current of 23 A, 11.4 ns pulses with a maximum pulse energy of ≈1.9 µJ and a maximum peak power of ≈166 W are achieved. The beam quality factor is measured to be M x 2=19.5 in the slow axis direction and M y 2=2.17 in the fast axis direction. Moreover, maximum average output power stability is confirmed, with a power fluctuation of less than 0.8% rms over 60 min. To the best of our knowledge, this is the first high-energy external-cavity dumped demonstration from an UBALD.

A novel model based on liver/spleen volumes and portal vein diameter on MRI to predict variceal bleeding in HBV cirrhosis.

OBJECTIVE: To develop a novel logistic regression model based on liver/spleen volumes and portal vein diameter measured on magnetic resonance imaging (MRI) for predicting oesophagogastric variceal bleeding (OVB) secondary to HBV cirrhosis. METHODS: One hundred eighty-five consecutive cirrhotic patients with hepatitis B undergoing abdominal contrast-enhanced MRI were randomly divided into training cohort (n = 130) and validation cohort (n = 55). Spleen volume, total liver volume, four liver lobe volumes, and diameters of portal venous system were measured on MRI. Ratios of spleen volume to total liver and to individual liver lobe volumes were calculated. In training cohort, univariate analyses and binary logistic regression analyses were to determine independent predictors. Performance of the model for predicting OVB constructed based on independent predictors from training cohort was evaluated by receiver operating characteristic (ROC) analysis, and was validated by Kappa test in validation cohort. RESULTS: OVB occurred in 42 and 18 individuals in training and validation cohorts during the 2 years' follow-up, respectively. An OVB prediction model was constructed based on the independent predictors including right liver lobe volume (RV), left gastric vein diameter (LGVD) and portal vein diameter (PVD) (odds ratio = 0.993, 2.202 and 1.613, respectively; p-values < 0.001 for all). The logistic regression model equation (-0.007 × RV + 0.79 × LGVD + 0.478 × PVD-6.73) for predicting OVB obtained excellent performance with an area under ROC curve of 0.907. The excellent performance was confirmed by Kappa test with K-value of 0.802 in validation cohort. CONCLUSION: The novel logistic regression model can be reliable for predicting OVB. KEY POINTS: • Patients with oesophagogastric variceal bleeding are mainly characterized by decreased right lobe volume, and increased spleen volume and diameters of portal vein system. • The right liver lobe volume, left gastric vein diameter and portal vein diameter are the independent predictors of oesophagogastric variceal bleeding. • The novel model developed based on the independent predictors performed well in predicting oesophagogastric variceal bleeding with an area under the receiver operating characteristic curve of 0.907.

Cascade N2 Reduction Process with DBD Plasma Oxidation and Electrocatalytic Reduction for Continuous Ammonia Synthesis.

Due to the extremely high bond energy of N≡N (∼941 kJ/mol), the traditional Haber-Bosch process of ammonia synthesis is known as an energy-intensive and high CO2-emission industry. In this paper, a cascade N2 reduction process with dielectric barrier discharge (DBD) plasma oxidation and electrocatalytic reduction as an alternative route is first proposed. N2 is oxidized to be reactive nitrogen species (RNS) by nonthermal plasma, which would then be absorbed by KOH solution and electroreduced to NH4+. It is found that the production of NOx is a function of discharge length, discharge power, and gas flow rate. Afterward, the cobalt catalyst is used in the process of electrocatalytic reduction of ammonia, which shows high selectivity (Faradic efficiency (FE) above 90%) and high yield of ammonia (45.45 mg/h). Finally, the cascade plasma oxidation and electrocatalytic reduction for ammonia synthesis is performed. Also, the performance of the reaction system is evaluated. It is worth mentioning that a stable and sustainable ammonia production efficiency of 16.21 mg/h is achieved, and 22.16% of NOx obtained by air activation is converted into NH4+. This work provides a demonstration for further industrial application of ammonia production with DBD plasma oxidation and electrocatalytic reduction techniques.

CT Features of Recurrent Acute Pancreatitis: Early Phase Versus Late Phase.

OBJECTIVES: The aim of this study was to investigate the computed tomography (CT) features of recurrent acute pancreatitis (RAP) in the early phase and late phase. METHODS: Recurrent acute pancreatitis data were obtained over the past 5 years. Recurrent acute pancreatitis patients were divided into 2 groups according to the time from RAP onset to performing CT examination: the early phase (first week) and late phase (after the first week) based on the 2012 revised Atlanta classification (RAC). Evaluation and comparison of patients' demographic data, RAC, CT findings, CT severity index (CTSI) score, and extrapancreatic inflammation on CT (EPIC) score were conducted in the 2 groups. RESULTS: Hypertriglyceridemia was the most common cause of RAP in 679 of 686 patients (positive CT rate: 98.98%). Among 679 CT-positive patients, interstitial edematous pancreatitis and necrotizing pancreatitis accounted for 61.71% (419/679) and 38.29% (260/679), respectively. The CTSI and EPIC scores were higher in the late phase than in the early phase (both P 's < 0.05). The proportion of moderately severe and severe RAP patients based on RAC was higher in the late phase than in the early phase ( P < 0.05). Early-stage EPIC score was more accurate than CTSI and Acute Physiology and Chronic Health Evaluation (APACHE) II scores in predicting clinically severe RAP (EPIC vs CTSI; EPIC vs APACHE II, both P 's < 0.05). CONCLUSIONS: Recurrent acute pancreatitis is more severe in the late phase than in the early phase. The EPIC score is more indicative of clinically severe RAP than CTSI and APACHE II scores in the early phase of RAP.

Comparison of the imaging and clinical characteristics between Initial and Recurrent Alcoholic Acute Pancreatitis: a retrospective cross-sectional study.

MATERIALS: Patients with alcoholic acute pancreatitis in our hospital were recruited from Jan 2019 to July 2022 and divided into IAAP and RAAP groups. All patients underwent Contrast-Enhanced Computerized Tomography (CECT) or Magnetic Resonance Imaging (MRI) after administration. Imaging manifestations, local complications, severity scores on the Modified CT/MR Severity Index (MCTSI/MMRSI), Extrapancreatic Inflammation on CT/MR (EPIC/M), clinical severity [Bedside Index for Severity in Acute Pancreatitis (BISAP) Acute Physiology and Chronic Health Evaluation (APACHE-II)], and clinical prognosis were compared between the two groups.Results: 166 patients were recruited for this study, including 134 IAAP (male sex 94%) and 32 RAAP patients (male sex 100%). On CECT or MRI, IAAP patients were more likely to develop ascites and Acute Necrosis collection (ANC) than RAAP patients (ascites:87.3%vs56.2%; P = .01; ANC:38%vs18.7%; P < .05). MCTSI/MMRSI and EPIC/M scores were higher in IAAP than in RAAP patients(MCTSI/MMRSI:6.2vs5.2; P < .05; EPIC/M:5.4vs3.8; P < .05).Clinical severity scores (APACHE-II and BISAP), length of stay, and systemic complications [Systemic Inflammatory Response Syndrome (SIRS), respiratory failure] were higher in the IAAP group than in the RAAP group (P < .05). No mortality outcomes were reported in either group while hospitalized.Conclusions: Patients with IAAP had more severe disease than those with RAAP. These results may be helpful for differentiating care paths for IAAP and RAAP, which are essential for management and timely treatment in clinical practice.

Distribution and density of tertiary lymphoid structures predict clinical outcome in intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: The prognostic value and clinical relevance of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA) remain unclear. Thus, we aimed to investigate the prognostic value and functional involvement of TLSs in iCCA. METHODS: We retrospectively included 962 patients from 3 cancer centers across China. The TLSs at different anatomic subregions were quantified and correlated with overall survival (OS) by Cox regression and Kaplan-Meier analyses. Multiplex immunohistochemistry (mIHC) was applied to characterize the composition of TLSs in 39 iCCA samples. RESULTS: A quaternary TLS scoring system was established for the intra-tumor region (T score) and peri-tumor region (P score) respectively. T scores positively correlated with favorable prognosis (p <0.001), whereas a high P score signified worse survival (p <0.001). mIHC demonstrated that both T follicular helper and regulatory T cells were significantly increased in intra-tumoral TLSs compared to peri-tumoral counterparts (p <0.05), and regulatory T cell frequencies within intra-tumoral TLSs were positively associated with P score (p <0.05) rather than T score. Collectively, the combination of T and P scores stratified iCCAs into 4 immune classes with distinct prognoses (p <0.001) that differed in the abundance and distribution pattern of TLSs. Patients displaying an immune-active pattern had the lowest risk, with 5-year OS rates of 68.8%, whereas only 3.4% of patients with an immune-excluded pattern survived at 5 years (p <0.001). The C-index of the immune class was statistically higher than the TNM staging system (0.73 vs. 0.63, p <0.001). These results were validated in an internal and 2 external cohorts. CONCLUSIONS: The spatial distribution and abundance of TLSs significantly correlated with prognosis and provided a useful immune classification for iCCA. T follicular helper and regulatory T cells may play a critical role in determining the functional orientation of spatially different TLSs. LAY SUMMARY: Tertiary lymphoid structures (TLSs) are associated with favorable prognosis in a number of cancers. However, their role in intrahepatic cholangiocarcinoma (iCCA) remains unclear. Herein, we comprehensively evaluated the spatial distribution, abundance, and cellular composition of TLSs in iCCA, and revealed the opposite prognostic impacts of TLSs located within or outside the tumor. This difference could be mediated by the different immune cell subsets present within the spatially distinct TLSs. Based on our analysis, we were able to stratify iCCAs into 4 immune subclasses associated with varying prognoses.

Quantum State Preparation with Optimal Circuit Depth: Implementations and Applications.

Quantum state preparation is an important subroutine for quantum computing. We show that any n-qubit quantum state can be prepared with a Θ(n)-depth circuit using only single- and two-qubit gates, although with a cost of an exponential amount of ancillary qubits. On the other hand, for sparse quantum states with d⩾2 nonzero entries, we can reduce the circuit depth to Θ(log(nd)) with O(ndlogd) ancillary qubits. The algorithm for sparse states is exponentially faster than best-known results and the number of ancillary qubits is nearly optimal and only increases polynomially with the system size. We discuss applications of the results in different quantum computing tasks, such as Hamiltonian simulation, solving linear systems of equations, and realizing quantum random access memories, and find cases with exponential reductions of the circuit depth for all these three tasks. In particular, using our algorithm, we find a family of linear system solving problems enjoying exponential speedups, even compared to the best-known quantum and classical dequantization algorithms.

Catalytic Enantioselective Steglich-Type Rearrangement of Enol Lactones: Asymmetric Synthesis of Spirocyclic 1,3-Diketones.

An example of asymmetric Steglich-type rearrangement of enol lactones is reported. This highly enantioselective acyl transfer reaction is catalyzed by chiral isothiourea at ambient temperature and provides a useful synthetic approach to access enantioenriched spirotricyclic ß,ß'-diketones from a broad range of indanone or tetralone-derived lactones. Preliminary mechanistic studies suggest the initial formation of an N-acylated iminium cation intermediate that induces a following facial selective condensation.

The association between handgrip strength and depression in cancer survivors: a cross-sectional study.

BACKGROUND: The association between handgrip strength and depression in cancer survivors has been unexplored until now. We aim to examine the association between handgrip strength and depression in cancer survivors by using publicly available data (National Health and Nutrition Examination Survey). METHODS: Two waves of data from the National Health and Nutrition Examination Survey, from 2011-2012 and 2013-2014, were extracted and combined to explore this important issue. We extracted maximum patient handgrip strength value (from both hands). The Patient Health Questionnaire (PHQ-9) was used to evaluate depression with a cut-off > = 10 points indicating that patients had depressive symptoms. Other basic characteristics and health-related variables were also collected. We used Least Absolute Shrinkage and Selection Operator (LASSO) regression to select potential confounding factors. Multivariable linear or logistic regression models were adopted to explore whether handgrip strength as a continuous variable, or low handgrip strength, was associated with depressive symptoms. RESULTS: There were 876 cancer survivors in our present total sample, with 403 (46.0%) males and 473 females (54.0%). The mean (SD) age of the entire group was 64.67 (13.81) years. The prevalence of depression and low handgrip strength was 12.90% and 16.7%, respectively. The results showed that handgrip strength was negatively associated with depressive symptoms in cancer survivors (OR = 0.95, 95%CI:0.92-0.99; P = 0.024). In addition, after adjusting for age, gender, race; marital status, polypharmacy, sleep disorder, arthritis, congestive heart failure, history of stroke, type of cancer, chronic coronary bronchitis and being overweight, cancer survivors with low handgrip strength had a 2.02-fold risk of depression, compared to those with normal handgrip strength (OR = 2.02,95%CI:1.07-3.81; P = 0.028). CONCLUSIONS: Our present study suggests that low handgrip strength, as a simple and modifiable parameter, is associated with a higher risk of depression in cancer survivors. Therefore, future larger-scale prospective cohort studies are warranted to determine this association.

The association between frailty and mortality among lower limb arthroplasty patients: a systematic review and meta-analysis.

BACKGROUND: Some studies associate frailty and postoperative mortality in hip or knee replacement patients, and others have explored the relationship between the frailty index and changes in postoperative mortality in hip or knee replacement patients, but their findings are not consistent. This meta-analysis and systematic review aimed to pool the results of existing studies to explore whether frailty is an independent risk factor for postoperative mortality in patients with lower limb arthroplasty (including hip or knee arthroplasty). METHODS: On December 15, 2021, we searched the relevant articles from the PubMed, Embase, Medline (via Ovid), China National Knowledge Infrastructure (CNKI) and Wan Fang Med Online databases. We used the Newcastle-Ottawa Scale (NOS) to assess the quality of the articles that met the exclusion and inclusion criteria. R Studio was used to analyze the effect sizes (based on the random model integration) on the extracted data. Meanwhile, potential publication bias and sensibility analysis were performed. RESULTS: We included seven studies, which included a total of 460,594 patients, for quantitative analysis. Overall, frailty increased the risk of mortality in lower limb arthroplasty patients compared to those without frailty, as measured by a pooled risk ratio (RR) of 2.46 (95% confidence interval [CI]: 1.81-3.33). Additionally, subgroup analysis based on population revealed that the pooled RRs for total knee arthroplasty (TKA) patients in three studies and total hip arthroplasty (THA) patients in four studies were 2.61 (95% CI: 2.26-3.02) and 3.18 (95% CI: 1.92-5.28), respectively, for TKA patients in three studies and THA patients in four studies. Additionally, these statistically significant positive associations persisted in subgroup analyses by study design, geographic region, and follow-up period. CONCLUSION: Frailty is an independent risk factor for postoperative mortality in patients undergoing lower limb arthroplasty, according to our findings. This suggests that frailty may be a predictor of preoperative risk stratification for patients with such elective surgery and could alert doctors and nurses of early screening and medical care interventions in patients with such a need for surgery to reduce postoperative mortality in lower limb arthroplasty patients.

The association between the number of teeth and frailty among older nursing home residents: a cross-sectional study of the CLHLS survey.

BACKGROUND: Given that few studies have explored the association between oral health and frailty among older nursing home residents, the purpose of this study was to assess the association between oral health (i.e., the number of teeth and oral behaviors) and frailty in this population using the Chinese Longitudinal Healthy Longevity Survey (CLHLS). METHODS: This was a national cross-sectional study derived from the seventh wave of CLHLS in 2018, consisting of 365 older nursing home residents aged 65 years or older. The frailty index was constructed based on 32 variables consisting of self-rated health status, anxiety, depression, ADL and IADL. Oral health was measured through the number of natural teeth and tooth brushing behavior. Multiple logistic regression was used to identify this association between the number of teeth, oral health behaviors, and frailty. RESULTS: The mean age of this sample was 87.6 (SD = 9.5), with 154 (42.2%) males. The prevalence of frailty and edentulism was 71.2% and 33.4%, respectively. Multiple logistic regression analysis found that the likelihood of frailty decreased with an increased number of teeth, with an OR of 0.94 (95% CI: 0.91-0.98). Compared with participants with edentulism, older adults with 1 to 20 teeth had a lower likelihood of frailty (OR = 0.39, 95% CI: 0.17-0.88); these results were also found in older adults with more than 20 teeth (OR = 0.20, 0.07-0.57). Additionally, older adults who brush their teeth regularly have a lower likelihood of frailty than those who never brush their teeth (OR = 0.37, 95% CI: 0.13-0.99). CONCLUSION: Older nursing home residents who maintain their natural teeth can help lower the risk of frailty, and regular toothbrushing also contributes to decreasing the risk of frailty. Our study emphasizes the importance of oral health, and cohort studies with large-scale samples to address this important issue are warranted in the future.

B cell subsets were associated with prognosis in elderly patients with community acquired pneumonia.

BACKGROUND: The role of B cell subsets remained to be elucidated in a variety of immune diseases, though which was used as an effective biomarker for anti-inflammatory or antiviral response. This study aimed to evaluate the early changes of B cell subtypes distribution in elderly patients with community acquired pneumonia (CAP), as well as the association between B cell subtypes and prognosis. METHODS: This prospective study included elderly patients with CAP, severe CAP (sCAP) and healthy elderly subjects between April 2016 and March 2018. Flow cytometry was used to detect CD3, CD20, HLA-DR, CD24, CD27, CD38, IgM, and IgD. CD20+ B cells were further divided into naïve B cells (Bn), IgM/D+ memory B cells (IgM+ Bm), switched B cells (SwB), and transitional B cells (Btr). RESULTS: A total of 22 healthy controls, 87 patients with CAP and 58 patients with sCAP were included in the study. Compared to CAP, sCAP was characterized by significantly lower absolute number of B cells, Bn and Btr, significantly lower Btr and Bn subset percentage, while percentage of IgM+ Bm was significantly higher. Heat map showed Bn and Btr on day 3 and day 7 was negatively correlated with activated partial prothrombin time (APTT), international normalized ratio (INR), sequential organ failure assessment score (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II). After 28-day follow-up, Btr percentage in survival group was significantly higher. Receiver operator characteristic (ROC) curve analysis found that Btr count showed sensitivity of 48.6% and specificity of 87.0% for predicting the 28-day survival, with an area under the ROC curves of 0.689 (p = 0.019). CONCLUSIONS: Severity and prognosis of CAP in elderly people is accompanied by changes in the B cell subsets. Btr subsets could play prognostic role for a short-term mortality of elderly CAP patients.

Chiral 1,2,3-Triazolium Salt Catalyzed Asymmetric Mono- and Dialkylation of 2,5-Diketopiperazines with the Construction of Tetrasubstituted Carbon Centers.

Novel asymmetric mono- and dialkylation reactions of α-substituted 2,5-diketopiperazines catalyzed by new chiral spirocyclic-amide-derived triazolium organocatalysts have been developed, resulting in a range of enantioenriched 2,5-diketopiperazine derivatives containing one or two tetrasubstituted carbon stereocenters. The reactions feature high yields (up to 98%), and excellent cis-diastereo- and enantioselectivities (up to >20:1 dr, >99 % ee), and they provide a new asymmetric synthetic approach to important functionalized 2,5-diketopiperazine skeletons. Furthermore, a possible reaction mechanism was proposed based on both control experiments and extensive DFT calculations.

Experimental Quantum Target Detection Approaching the Fundamental Helstrom Limit.

Quantum target detection is an emerging application that utilizes entanglement to enhance the sensing of the presence of an object. Although several experimental demonstrations for certain situations have been reported recently, the single-shot detection limit imposed by the Helstrom limit has not been reached because of the unknown optimum measurements. Here we report an experimental demonstration of quantum target detection, also known as quantum illumination, in the single-photon limit. In our experiment, one photon of the maximally entangled photon pair is employed as the probe signal and the corresponding optimum measurement is implemented at the receiver. We explore the detection problem in different regions of the parameter space and verify that the quantum advantage exists even in a forbidden region of the conventional illumination, where all classical schemes become useless. Our results indicate that quantum illumination breaks the classical limit for up to 40%, while approaching the quantum limit imposed by the Helstrom limit. These results not only demonstrate the advantage of quantum illumination, but also manifest its valuable potential of target detection.

Experimental Quantum State Measurement with Classical Shadows.

A crucial subroutine for various quantum computing and communication algorithms is to efficiently extract different classical properties of quantum states. In a notable recent theoretical work by Huang, Kueng, and Preskill [Nat. Phys. 16, 1050 (2020)NPAHAX1745-247310.1038/s41567-020-0932-7], a thrifty scheme showed how to project the quantum state into classical shadows and simultaneously predict M different functions of a state with only O(log_{2}M) measurements, independent of the system size and saturating the information-theoretical limit. Here, we experimentally explore the feasibility of the scheme in the realistic scenario with a finite number of measurements and noisy operations. We prepare a four-qubit GHZ state and show how to estimate expectation values of multiple observables and Hamiltonians. We compare the measurement strategies with uniform, biased, and derandomized classical shadows to conventional ones that sequentially measure each state function exploiting either importance sampling or observable grouping. We next demonstrate the estimation of nonlinear functions using classical shadows and analyze the entanglement of the prepared quantum state. Our experiment verifies the efficacy of exploiting (derandomized) classical shadows and sheds light on efficient quantum computing with noisy intermediate-scale quantum hardware.

Noninvasive evaluation of early diabetic nephropathy using diffusion kurtosis imaging: an experimental study.

OBJECTIVES: To evaluate the value of renal diffusion kurtosis imaging (DKI) in the diagnosis of early diabetic nephropathy (DN) in a rat model. MATERIALS AND METHODS: Forty male Zucker diabetic fatty rats that spontaneously developed type 2 diabetes mellitus (DM) and 20 age-matched nondiabetic lean Zucker rats were included. Renal DKI scans and histological examinations were performed on the rats in batches at the end of the 4th, 8th, 12th, 16th, and 20th week after DM model was built. Based on renal histopathological appearance, included animals were divided into three groups: a nondiabetic control group, a DM group without DN, and an early DN group. Mean kurtosis (MK) and mean diffusivity (MD) values of renal cortex and medulla were analyzed statistically. RESULTS: MK values of renal cortex and medulla tended to increase from the control group to the early DN group, respectively, while MD values tended to decrease. The cutoff MD and MK values of renal cortex and medulla showed different values in discriminating early DN from controls. Among them, cutoff MK value of medulla of 0.62 was the best parameter (sensitivity, 93.9%; specificity, 96.4%; and area under the curve, 0.95). For discriminate early DN from DM without DN and DM without DN from controls, cutoff MK value of renal cortex or medulla achieved an area under the curve of 0.76-0.85. CONCLUSIONS: MR DKI may be valuable for the noninvasive detection of early DN, and MK value might serve as a more sensitive biomarker of early DN than MD value. KEY POINTS: • In this article, diffusion kurtosis imaging (DKI) was used to detect the changes in the kidneys due to early diabetic nephropathy (DN). • MR DKI may be valuable for the noninvasive detection of early DN. • The mean kurtosis values of renal cortex and medulla might serve as a more sensitive biomarker of early DN than the mean diffusivity values.

Effect of cardiopulmonary bypass reoxygenation on myocardial dysfunction following pediatric tetralogy of Fallot repair.

BACKGROUND: Little is known regarding the effect of cardiopulmonary bypass (CPB) reoxygenation on cardiac function following tetralogy of Fallot repair. We hypothesized that hyperoxic reoxygenation would be more strongly associated with myocardial dysfunction in children with tetralogy of Fallot. METHODS: We investigated the association of perfusate oxygenation (PpO2) associated with myocardial dysfunction among children aged 6-72 months who underwent complete repair of tetralogy of Fallot in 2012-2018. Patients were divided into two groups: lower PpO2 group (≤ 250 mmHg) and higher PpO2 (> 250 mmHg) group based on the highest value of PpO2 during aortic occlusion. The odd ratio (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. RESULTS: This study included 163 patients perfused with lower PpO2 and 213 with higher PpO2, with median age at surgery 23.3 (interquartile range [IQR] 12.5-39.4) months, 164 female (43.6%), and median body mass index 15.59 (IQR 14.3-16.9) kg/m2. After adjustment for baseline, clinical and procedural variables, patients with higher PpO2 were associated with higher risk of myocardial dysfunction than those with lower PpO2 (OR 1.770; 95% CI 1.040-3.012, P = 0.035). Higher PpO2, lower SpO2, lower pulmonary annular Z-score, and longer CPB time were independent risk factors for myocardial dysfunction. CONCLUSIONS: Association exists between higher PpO2 and myocardial dysfunction risk in patients with tetralogy of Fallot, highlighting the modulation of reoxygenation during aortic occlusion to reduce cardiovascular damage following tetralogy of Fallot repair. TRIAL REGISTRATION: Clinical Trials. gov number NCT03568357. June 26, 2018.