Suicide death, suicidal ideation and suicide attempt in patients with diabetes: A systematic review and meta-analysis.

AIMS: Diabetes has been indicated to be a risk factor for suicide. We aim to estimate the prevalence of suicide in patients with diabetes. DESIGN: A meta-analysis using PRISMA methodology was adopted to examine the incidence of suicide in diabetic patients. DATA SOURCES: From inception to October 2022, three online databases (PubMed, China National Knowledge Infrastructure and Web of Science) were used to search studies. REVIEW METHODS: We used random-effects model to analysis. And our primary outcome was the incidence of suicide death per 100 person-years, and other outcomes were prevalence of suicidal ideation and suicide attempt. To explore the sources of heterogeneity in our study, we performed subgroup and meta-regression analyses. RESULTS: The suicide death rate in diabetic patients was 0.027 per 100 person-years, with a higher rate for Type 1 Diabetes Mellitus compared to Type 2 Diabetes Mellitus. The prevalence of suicidal ideation in diabetes patients was 0.175, with a higher prevalence in Type 1 Diabetes Mellitus compared to Type 2 Diabetes Mellitus. The prevalence of suicide attempts in diabetes patients was 0.033, indicating a higher rate for Type 2 Diabetes Mellitus compared to Type 1 Diabetes Mellitus. CONCLUSIONS: The results indicate a high rate of suicide among people with diabetes, and this study identifies populations and regions at high risk for suicide. Our review emphasizes interventions in mental health and the improvement of suicide prevention programmes. IMPACT: The study investigated suicide death, suicidal ideation and suicide attempt in diabetic individuals. Suicide rates are elevated among diabetic patients, and various patient groups face distinct suicide risks. It is important to prioritize the mental well-being of diabetic individuals and enhance interventions, including personalized approaches, to inform public health efforts aimed at preventing and addressing suicide among diabetic patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Prognostic Value of Left Ventricular Longitudinal Function and Myocardial Fibrosis in Patients With Ischemic and Non-Ischemic Dilated Cardiomyopathy Concomitant With Type 2 Diabetes Mellitus: A 3.0 T Cardiac MR Study.

BACKGROUND: Poorly controlled type 2 diabetes mellitus (T2DM) is known to result in left ventricular (LV) dysfunction, myocardial fibrosis, and ischemic/nonischemic dilated cardiomyopathy (ICM/NIDCM). However, less is known about the prognostic value of T2DM on LV longitudinal function and late gadolinium enhancement (LGE) assessed with cardiac MRI in ICM/NIDCM patients. PURPOSE: To measure LV longitudinal function and myocardial scar in ICM/NIDCM patients with T2DM and to determine their prognostic values. STUDY TYPE: Retrospective cohort. POPULATION: Two hundred thirty-five ICM/NIDCM patients (158 with T2DM and 77 without T2DM). FIELD STRENGTH/SEQUENCE: 3T; steady-state free precession cine; phase-sensitive inversion recovery segmented gradient echo LGE sequences. ASSESSMENT: Global peak longitudinal systolic strain rate (GLPSSR) was evaluated to LV longitudinal function with feature tracking. The predictive value of GLPSSR was determined with ROC curve. Glycated hemoglobin (HbA1c) was measured. The primary adverse cardiovascular endpoint was follow up every 3 months. STATISTICAL TESTS: Mann-Whitney U test or student's t-test; Intra and inter-observer variabilities; Kaplan-Meier method; Cox proportional hazards analysis (threshold = 5%). RESULTS: ICM/NIDCM patients with T2DM exhibited significantly lower absolute value of GLPSSR (0.39 ± 0.14 vs. 0.49 ± 0.18) and higher proportion of LGE positive (+) despite similar LV ejection fraction, compared to without T2DM. LV GLPSSR was able to predict primary endpoint (AUC 0.73) and optimal cutoff point was 0.4. ICM/NIDCM patients with T2DM (GLPSSR < 0.4) had more markedly impaired survival. Importantly, this group (GLPSSR < 0.4, HbA1c ≥ 7.8%, or LGE (+)) exhibited the worst survival. In multivariate analysis, GLPSSR, HbA1c, and LGE (+) significantly predicted primary adverse cardiovascular endpoint in overall ICM/NIDCM and ICM/NIDCM patients with T2DM. CONCLUSIONS: T2DM has an additive deleterious effect on LV longitudinal function and myocardial fibrosis in ICM/NIDCM patients. Combining GLPSSR, HbA1c, and LGE could be promising markers in predicting outcomes in ICM/NIDCM patients with T2DM. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: 5.

Dynamic changes in cardiac morphology, function, and diffuse myocardial fibrosis duration of diabetes in type 1 and type 2 diabetic mice models using 7.0 T CMR and echocardiography.

Background: Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Hence, early detection of cardiac changes by imaging is crucial to reducing cardiovascular complications. Purpose: Early detection of cardiac changes is crucial to reducing cardiovascular complications. The study aimed to detect the dynamic change in cardiac morphology, function, and diffuse myocardial fibrosis(DMF) associated with T1DM and T2DM mice models. Materials and methods: 4-week-old C57Bl/6J male mice were randomly divided into control (n=30), T1DM (n=30), and T2DM (n=30) groups. A longitudinal study was conducted every 4 weeks using serial 7.0T CMR and echocardiography imaging. Left ventricular ejection fraction (LV EF), tissue tracking parameters, and DMF were measured by cine CMR and extracellular volume fraction (ECV). Global peak circumferential strain (GCPS), peak systolic strain rate (GCPSSR) values were acquired by CMR feature tracking. LV diastolic function parameter (E/E') was acquired by echocardiography. The correlations between the ECV and cardiac function parameters were assessed by Pearson's test. Results: A total of 6 mice were included every 4 weeks in control, T1DM, and T2DM groups for analysis. Compared to control group, an increase was detected in the LV mass and E/E' ratio, while the values of GCPS, GCPSSR decreased mildly in DM. Compared to T2DM group, GCPS and GCPSSR decreased earlier in T1DM(GCPS 12W,P=0.004; GCPSSR 12W,P=0.04). ECV values showed a significant correlation with GCPS and GCPSSR in DM groups. Moreover, ECV values showed a strong positive correlation with E/E'(T1DM,r=0.757,P<0.001;T2DM, r=0.811,P<0.001). Conclusion: The combination of ECV and cardiac mechanical parameters provide imaging biomakers for pathophysiology, early diagnosis of cardiac morphology, function and early intervention in diabetic cardiomyopathy in the future.

Melittin-Carrying Nanoparticle Suppress T Cell-Driven Immunity in a Murine Allergic Dermatitis Model.

Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are the most common human skin disorders. Although corticosteroids have been widely used to treat ACD and AD, the side effects of corticosteroids encourage researchers to explore new immunoregulatory treatments. Here, an immunomodulatory approach based on lipid nanoparticles carrying α-helical configurational melittin (α-melittin-NP) is developed to overcome T cell-mediated inflammatory reactions in an oxazolone (OXA)-induced contact hypersensitivity mouse model and OXA-induced AD-like mouse model. Intradermal injection of low-dose α-melittin-NPs prevents the skin damage caused by melittin administration alone and efficiently targeted lymph nodes. Importantly, melittin and α-melittin-NPs restrain RelB activity in dendritic cells (DCs) and further suppresses dendritic cell activation and maturation in lymph nodes. Furthermore, low-dose α-melittin-NPs leads to relief of antigen recognition-induced effector T cell arrest in the dermis and inhibited allergen-specific T cell proliferation and activation. Significantly, this approach successfully controls Th1-type cytokine release in the ACD model and restricts Th2-type cytokine and IgE release in the AD-like model. Overall, intradermal delivery of low-dose α-melittin-NPs efficiently elicits immunosuppression against T cell-mediated immune reactions, providing a promising therapeutic strategy for treating skin disorders not restricted to the lesion region.

Regulation of colony-stimulating factor 1 receptor inhibitor pexidartinib on the senescence of mouse bone marrow-derived macrophages stimulated by lipopolysaccharide / 中华口腔医学杂志

Objective: To investigate the effects of colony-stimulating factor 1 receptor (CSF-1R) inhibitor pexidartinib (PLX3397) on the senescence of bone marrow-derived macrophages (BMDM) stimulated by lipopolysaccharide (LPS). Methods: BMDM were isolated and cultured from femurs and tibiae of 10 male C57BL/6 mice aged 6-8 weeks (obtained from Laboratory Animal Center of Guizhou Medical University). They were divided into blank control group, LPS group (treated with 1 μg/ml LPS for 24 h) as well as low, medium and high concentration PLX3397 pretreatment groups (treated with 100, 500 and 1 000 nmol/L PLX3397 for 4 h respectively followed by 1 μg/ml LPS for 24 h). The corresponding markers of macrophages were detected by flow cytometry. Cell viability was detected by cell counting kit-8 and cellular senescence was detected by senescence-associated-β-galactosidase (SA-β-gal) staining. Meanwhile, protein expressions of cycle-dependent kinase inhibitor p16, p21 and CSF-1R were detected by Western blotting, and the expressions of p16 and p21 were detected by intracellular immunofluorescence. Real-time fluorescence quantitative PCR (RT-qPCR) was used to investigate the mRNA levels of senescence-associated secretory phenotype (SASP) genes including interleukin (IL), IL-1β, chemokine-1/10 (CXCL-1/10), matrix metalloproteinase-8 (MMP-8), and transforming growth factor-β (TGF-β). Results: The rate of SA-β-gal positive staining in medium and high concentration PLX3397 pretreatment groups [(39.33±4.93)% and (36.33±3.06)% respectively] were significantly downregulated compared with LPS group [(52.00±3.00)%] (P=0.020, P=0.005). The expression of CSF-1R protein in low, medium and high concentration PLX3397 pretreatment groups were (0.74±0.18, 0.61±0.07, 0.54±0.06), all of which were significantly lower than that in LPS group (1.16±0.08) (P=0.013, P=0.002, P<0.001). The expression levels of CSF-1R mRNA in low, medium and high concentration PLX3397 pretreatment groups (1.04±0.06, 0.90±0.05, 1.18±0.08) showed similar trend (2.90±0.25) (P<0.001). The average fluorescence intensity of p16 in all PLX3397 pretreatment groups were 49.76±3.65, 48.21±1.72, 47.99±1.26 respectively, which were significantly lower than that in LPS group (66.88±5.85) (P=0.001, P<0.001, P<0.001). The average fluorescence intensity of p21 in medium and high concentration PLX3397 pretreatment groups were (34.43±3.62, 30.13±0.86), significantly lower than that in LPS group (46.82±5.33) (P=0.043, P=0.007). The expression of p16 protein in low, medium and high concentration PLX3397 pretreatment groups (0.56±0.04, 0.55±0.04, 0.35±0.19) were significantly lower than that in LPS group (0.98±0.10) (P=0.003, P=0.002, P<0.001), as well the expression of p21 protein (0.69±0.20, 0.42±0.08, 0.26±0.14) (P=0.032, P=0.002, P<0.001). According to the results of RT-qPCR, the expressions of IL-6, IL-1β, CXCL-1, CXCL-10 and MMP-8 in PLX3397 pretreatment groups were significantly lower than those in LPS group (P<0.001), while the expression of TGF-β increased (P<0.001). Conclusions: LPS could induce the cell senescence, increase the secretion of SASP and aggravate local inflammation by activating the CSF-1R on the cell surface of bone marrow-derived macrophages. CSF-1R inhibitor PLX3397 might attenuate CSF-1R activation associated with LPS and inhibit the senescence of bone marrow-derived macrophages induced by LPS.

Mesoscale visualization of three-dimensional microvascular architecture and immunocyte distribution in intact mouse liver lobes.

Rational: The complex vascular architecture and diverse immune cells of the liver are critical for maintaining liver homeostasis. However, quantification of the network of liver vasculature and immunocytes at different scales from a single hepatic lobule to an intact liver lobe remains challenging. Methods: Here, we developed a fast and fluorescence-preserving transparency method, denoted liver-CUBIC, for systematic and integrated analysis of the microcirculation and the three-dimensional distribution of dendritic cells (DCs)/macrophages in intact liver lobes. Results: Whole-mount imaging at mesoscale revealed that the hepatic classical lobule preferred the oblate ellipsoid morphology in the mouse liver and exhibited hepatic sinusoids with heterogeneous arrangement and intricate loop structure. Liver fibrosis not only induces sinusoidal density increase but also promotes sinusoidal arrangement with increased sinusoidal branch and loop structure. Meanwhile, we found that CD11c+ DCs followed a lognormal distribution in the hepatic lobules, skewing toward lobular boundary in steady state. CCl4-induced chronic liver injury promoted CD11c+ DC rearrangement at the lobular border before the formation of liver fibrosis. Furthermore, through whole-mount imaging of tumor-immune cell-vascular crosstalk in intact lobes based on liver-CUBIC, we characterized an accumulation of CX3CR1+CCR2+F4/80+ macrophages at metastatic foci in early colorectal liver metastases. Importantly, colorectal cells secrete CCL2 to mobilize CX3CR1+CCR2+F4/80+ macrophages to accumulate at liver micrometastases, and the interruption of CCL2-induced macrophage accumulation inhibits early colonization of metastasis in the liver. Conclusions: Our investigation of the sinusoidal network and DC/macrophage arrangements through the liver-CUBIC approach and whole-mount imaging provide a powerful platform for understanding hepatic circulatory properties and immune surveillance in the liver.

Diagnostic value of autofluorescence laryngoscope in early laryngeal carcinoma and precancerous lesions: A systematic review and meta-analysis.

OBJECTIVE: We aim to evaluate the diagnostic value of autofluorescence laryngoscope (AFL) in early laryngeal carcinoma and precancerous lesions. aWe also assess the value of AFL in diagnosis of early laryngeal carcinoma and precancerous lesions in comparison with that of white light laryngoscope (WL). METHODS: The databases consisting of PubMed, Cochrane Library, Web of science and CNKI were systematically searched to find pertinent literatures of AFL in diagnosing early laryngeal carcinoma and precancerous lesions. We made a quality evaluation of every study we included using the modified Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The pooled sensitivities, specificities were calculated using Meta-Disc 1.4. And we estimated the summary receiver operating characteristic curves (SROC) and area under the curves (AUC). RESULTS: We finally included 23 studies. The results of AFL in diagnosing early laryngeal carcinoma and precancerous lesions showed higher sensitivity of 0.91 (95%CI: 0.89-0.93; χ²=43.78, p = 0.0025) and specificity of 0.80 (95%CI: 0.77-0.82; χ²=130.64, p = 0.000), and the weighted AUC of AFL was 0.948 ± 0.013 (95%CI: 0.921-0.974) and the diagnostic accuracy (Q*) was 0.887 ± 0.018. The sensitivity and specificity of WL were 0.74 (95%CI: 0.70-0.77; χ²=52.40, p = 0.000) and 0.89 (95%CI: 0.87-0.90; χ²=299.22, p = 0.000), and the weighted AUC of WL was 0.835 ± 0.029 (95%CI: 0.777-0.892) and the diagnostic accuracy (Q*) was 0.767 ± 0.027. CONCLUSION: The meta-analysis and systematic review suggested that AFL had high diagnostic value in early laryngeal carcinoma and precancerous lesions, and its diagnostic value was higher than that of WL. These results indicated that AFL can provide good guidance for the early detection of laryngeal carcinoma and precancerous lesions.

Simple transabdominal minimally invasive direct coronary artery bypass surgery with right gastroepiploic artery.

For three patients with isolated right coronary artery disease who had drug resistance and were intolerant to interventional therapy, simple transabdominal small incision bypass grafting of the right gastroepiploic artery and the posterior descending branch of the right coronary artery was conducted without cardiopulmonary. All three patients were discharged smoothly without complications, and were followed up for three months, during which time the myocardial bridges were unobstructed and the cardiac functions were good. The surgery needs no thoracotomy and the injury is small, and avoids influences of sternum and pericardium adhesion on other cardiac surgery in the future. The risk of median sternotomy can be avoided for patients undergoing reoperation for coronary artery bypass surgery.

Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors.

Based on the structural scaffolds of natural products, two series of flavonoid derivatives, for a total of twelve compounds, were designed and synthesized as potential human telomerase inhibitors. Using a modified TRAP-PCR assay, compound 5c exhibited the most potent inhibitory activity against human telomerase with an IC50 value of less than 50 µM. In vitro, the results demonstrated that compound 5c had potent anticancer activity against five classes of tumor cell lines. The molecular docking and molecular dynamics analyses binding to the human telomerase holoenzyme were performed to elucidate the binding mode of active compound 5c. This finding helps the rational design of more potent telomerase inhibitors based on the structural scaffolds of natural products.

Visualizing DC morphology and T cell motility to characterize DC-T cell encounters in mouse lymph nodes under mTOR inhibition.

Mammalian target of rapamycin (mTOR), a serine/threonine kinase orchestrating cellular metabolism, is a crucial immune system regulator. However, it remains unclear how mTOR regulates dendritic cell (DC) function in vivo, especially DC-T cell encounters, a critical step for initiating adaptive immune responses. We dynamically visualized DC-T contacts in mouse lymph node using confocal microscopy and established an encounter model to characterize the effect of mTOR inhibition on DC-T cell encounters using DC morphology. Quantitative data showed mTOR inhibition via rapamycin altered DC shape, with an increased form factor (30.17%) and decreased cellular surface area (20.36%) and perimeter (22.43%), which were associated with Cdc42 protein downregulation (52.71%). Additionally, DCs adopted a similar morphological change with Cdc42 inhibition via ZCL278 as that observed with mTOR inhibition. These morphologically altered DCs displayed low encounter rates with T cells. Time-lapse imaging data of T cell motility supported the simulated result of the encounter model, where antigen-specific T cells appeared to reduce arrest in the lymph nodes of rapamycin-pretreated mice relative to the untreated group. Therefore, mTOR inhibition altered DC morphology in vivo and decreased the DC-T cell encounter rate, as well as Cdc42 inhibition. By establishing an encounter model, our study provides an intuitive approach for the early prediction of DC function through morphological quantification of form factor and area.

Visualization of T Cell-Regulated Monocyte Clusters Mediating Keratinocyte Death in Acquired Cutaneous Immunity.

It remains unclear how monocytes are mobilized to amplify inflammatory reactions in T cell-mediated adaptive immunity. Here, we investigate dynamic cellular events in the cascade of inflammatory responses through intravital imaging of a multicolor-labeled murine contact hypersensitivity model. We found that monocytes formed clusters around hair follicles in the contact hypersensitivity model. In this process, effector T cells encountered dendritic cells under regions of monocyte clusters and secreted IFN-γ, which mobilizes CCR2-dependent monocyte interstitial migration and CXCR2-dependent monocyte cluster formation. We showed that hair follicles shaped the inflammatory microenvironment for communication among the monocytes, keratinocytes, and effector T cells. After disrupting the T cell-mobilized monocyte clusters through CXCR2 antagonization, monocyte activation and keratinocyte apoptosis were significantly inhibited. Our study provides a new perspective on effector T cell-regulated monocyte behavior, which amplifies the inflammatory reaction in acquired cutaneous immunity.

Synthesis, biological evaluation and structure-activity relationship studies of hederacolchiside E and its derivatives as potential anti-Alzheimer agents.

Inspired by the previously reported neuroprotective activity of hederacolchiside E (1), we synthesized hederacolchiside E for the first time along with eleven of its derivatives. The neuroprotective effects of these compounds were further evaluated against H2O2- and Aß1-42-induced injury using cell-based assays. The derivatives showed obvious differences in activity due to structural variations, and two of them exhibited better neuroprotective effects than 1 in the Aß1-42-induced injury model. Compound 7 was the most active derivative and had a relatively simple chemical structure. Moreover, 1 and 7 can significantly reduce the release of lactate dehydrogenase (LDH), level of intracellular reactive oxygen species (ROS) and extent of malondialdehyde (MDA) increase resulting from Aß1-42 treatment, which demonstrated that these kinds of compounds show neuroprotective effects in Alzheimer's disease (AD) models via modulating oxidative stress. Compound 7 could be used as promising lead for the development of a new type of neuroprotective agent against AD.

In vivo imaging the motility of monocyte/macrophage during inflammation in diabetic mice.

Diabetes, as a chronic metabolic disease, can impair the immune function of monocytes/macrophages (MMs). However, it is unclear how MM immune response to inflammation with the development of diabetes, and whether immune response around the inflammatory foci depends on the depth in tissue. Footpad provides a classical physiological site for monitoring cellular behavior during inflammation, but limited to the superficial dermis due to the strong scattering of footpad. Herein, we used confocal microscopy to monitor the motility of MMs in deeper tissue around inflammatory foci with the development of type 1 diabetic (T1D) mice through a switchable footpad skin optical clearing window. Delayed-type hypersensitivity (DTH) model was elicited on the footpad of T1D. Results demonstrated that progressive T1D led to the gradually potentiated MM recruitment and increased expression of monocyte chemoattractant protein-1 during DTH, but MM migration displacement, motion velocity and motility coefficient were significantly attenuated. Besides, MMs from the deeper dermis had a much larger migration displacement than those from superficial dermis at early stages of DTH but an opposite tendency at late stages for non-T1D, while progressive T1D obscured this difference gradually. This study will be helpful for investigating the influences of progressive metabolic diseases on immune response. MM motion trajectory at depth of superficial dermis and the deeper dermis at AOVA (heat-aggregated ovalbumin)-4 hours and AOVA-72 hours on non-T1D (A) and T1D-4 weeks (B). Mean motility coefficient (C) at the 2 depths. Data were pooled from 6 mice per group. *P < .05 and **P < .01 compared among different T1D disease durations. #P < .05 compared between different depths.

Design, Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase IX Inhibitory Evaluations of Novel N-Substituted-ß-d-Glucosamine Derivatives that Incorporate Benzenesulfonamides.

A series of novel N-substituted-ß-d-glucosamine derivatives that incorporate benzenesulfonamides were designed using a fragment-based drug design strategy. Each derivative was synthesized and evaluated in vitro for its inhibitory activity against human carbonic anhydrase (hCA) IX; several derivatives displayed desirable potency profiles against this enzyme. The molecular docking studies provided the design rationale and predicted potential binding modes for carbonic anhydrase (CA) IX and three target compounds, including the most potent inhibitor, compound 7f (IC50 = 10.01 nM). Moreover, the calculated Log P (cLog P) values showed that all the compounds tended to be hydrophilic. In addition, topological polar surface area (TPSA) value-based predictions highlighted the selectivity of these carbohydrate-based inhibitors for membrane-associated CA IX.

Stented elephant trunk procedure with left subclavian artery transposition for acute type B dissection with distal arch involvement.

OBJECTIVE: Complete or partial supra-aortic debranching, after thoracic endovascular aortic repair, is appealing treatment for complicated acute type B dissection (ABAD) with aortic arch involvement (AAI) because of reduced surgical trauma. However, unsatisfactory outcomes have been reported. We retrospectively reviewed our experience of left subclavian artery (LSCA) transposition with stented elephant trunk (SET) implantation for complicated ABAD with distal AAI. METHODS: From April 2011 to December 2014, 19 patients (all men; mean age: 44 years) who had complicated ABAD and distal AAI underwent LSCA transposition with SET implantation via a median sternotomy under hypothermic cardiopulmonary bypass with selective cerebral perfusion. Preoperative renal dysfunction was observed in 3 patients, visceral ischemia in 2 patients, and lower-limb ischemia in 1 patient. RESULTS: No in-hospital deaths occurred. Seventeen patients required mechanical ventilation for <24 hours, and 2 cases for <48 hours. The mean time of mechanical ventilation and duration of stay in the intensive care unit was 18 ± 6 hours and 44 ± 16 hours, respectively. Ischemia of the viscera and lower limbs after surgery was ameliorated. Continuous renal replacement therapy was not required in 3 patients who had preoperative renal dysfunction. Complete thrombosis of the false lumen at the distal end of the SET was observed in 17 of 18 (94.4%) patients during follow-up. CONCLUSIONS: This method preserves autologous brachiocephalic vessels, excludes the false lumen, promotes thrombosis and remodeling of the distal aorta, and repairs proximal aortic lesions simultaneously. Satisfactory surgical outcomes and follow-up results were achieved using LSCA transposition with SET implantation.

Surgery for acute type A dissection using total arch replacement combined with stented elephant trunk implantation: Preservation of autologous brachiocephalic vessels.

OBJECTIVE: Various techniques have been introduced to treat acute type A dissection during aortic arch reconstruction. We retrospectively reviewed our experience of total arch replacement, with implantation of a stented elephant trunk, using preservation of autologous brachiocephalic vessels in patients with acute type A dissection. METHODS: Between August 2011 and April 2013, 20 patients (16 men, 4 women; mean age, 45 ± 10 years, range, 24-62 years) with acute type A dissection underwent total arch replacement combined with stented elephant trunk implantation, using preservation of autologous brachiocephalic vessels under hypothermic cardiopulmonary bypass with selective antegrade cerebral perfusion. RESULTS: No in-hospital deaths occurred. A transient neurologic deficit occurred in 1 patient, who ultimately required tracheotomy. Reoperation was indicated in 1 patient for bleeding. All patients survived and were discharged. During the mean follow-up period of 26 ± 7 months, 1 patient underwent thoracoabdominal aortic replacement, and 1 patient was lost to follow up. The patency of the anastomotic site between the left subclavian artery and the left common carotid artery was confirmed on computed tomography scanning. CONCLUSIONS: This technique simplified hemostasis and anastomosis, reduced the size of the residual aortic wall, and preserved the autologous brachiocephalic vessels, yielding satisfactory surgical results. This technique is an alternative approach for suitable patients with acute type A dissection. However, outcomes are preliminary, and long-term follow up is required.

Continuous dry fermentation of swine manure for biogas production.

A down plug-flow anaerobic reactor (DPAR) was designed for the feasibility study on continuous dry fermentation of swine manure without any additional stirring. Using fresh swine manure as the feedstock with TS concentration (w/w) of 20%, 25%, 30%, and 35%, stable volumetric biogas production rates of 2.40, 1.92, 0.911, and 0.644L · (Ld)(-1) and biogas yields of 0.665, 0.532, 0.252, and 0.178 L g(-)(1)VS were obtained respectively, and the TS degradation rates were 46.5%, 45.4%, 53.2%, and 55.6%, respectively. With the increase of feedstock TS concentration, the concentration of ammonia nitrogen grew up to the maximum value of 3500 mg L(-1). Biogas production was obviously inhibited when the concentration of ammonia nitrogen was above 3000 mg L(-1). The maximal volumetric biogas production rate of 2.34 L ·(Ld)(-1) and biogas yield of 0.649 L g(-1)VS were obtained with TS concentration of 25% at 25°C without inhibition. Liquidity experiments showed that TS concentration of digestate could be less than 15.8%, and the flow rate of digestate more than 0.98 m s(-1) when the feedstock TS concentration was less than 35%, which indicated the digestate could be easily discharged from a DPAR. Therefore, it is feasible to conduct a continuous dry fermentation in a DPAR using fresh swine manure as the feedstock with TS concentration less than 35%, whereas the feedstock TS concentration should not exceed 30% to achieve the maximal biogas production rate and biogas yield.

Distinct dendritic spine and nuclear phases of calcineurin activation after exposure to amyloid-ß revealed by a novel fluorescence resonance energy transfer assay.

Calcineurin (CaN) activation is critically involved in the regulation of spine morphology in response to oligomeric amyloid-ß (Aß) as well as in synaptic plasticity in normal memory, but no existing techniques can monitor the spatiotemporal pattern of CaN activity. Here, we use a spectral fluorescence resonance energy transfer approach to monitor CaN activation dynamics in real time with subcellular resolution. When oligomeric Aß derived from Tg2576 murine transgenic neurons or human AD brains were applied to wild-type murine primary cortical neurons, we observe a dynamic progression of CaN activation within minutes, first in dendritic spines, and then in the cytoplasm and, in hours, in the nucleus. CaN activation in spines leads to rapid but reversible morphological changes in spines and in postsynaptic proteins; longer exposure leads to NFAT (nuclear factor of activated T-cells) translocation to the nucleus and frank spine loss. These results provide a framework for understanding the role of calcineurin in synaptic alterations associated with AD pathogenesis.