Search

Objectives: To identify the mechanism of in vivo development of carbapenem resistance in Klebsiella pneumoniae.Methods: Seven sequential isolates of K. pneumoniae were obtained from twin infants with pneumonia. Antimicrobial susceptibility testing was performed by agar dilution. Carbapenemases including KPC and ML were initially screened using phenotypic methods, and carbapenemase-encoding genes were identified by PCR and amplicon sequencing. Plasmids of all clinical isolates and the conjugants of resistant isolates were estimated by S1 pulsed-field gel electrophoresis (PFGE). Molecular typing were conducted by PFGE of XbaI-digested genomic DNA and multilocus sequence typing (MLST). Results: For old brother, the first and third isolates were susceptible to meropenem, whereas the second and fourth isolates were resistant (MICs 16 mg/L). The first and second isolates from the young brother were susceptible to meropenem whereas the third isolate was resistant. All the resistant isolates produced NDM-1 metallo--lactamase. PFGE of XbaI-digested DNA revealed identical patterns for all the 7 isolates. All the isolates had the same sequence type named sequence type 37 (ST37). Conclusions: To our knowledge, this is the first documented case of development of carbapenem resistance in vivo mediated by NDM-1 metallo-b-lactamase in K. pneumoniae during treatment of pneumonia with meropenem.

The cost of next-generation sequencing is now approaching that of early GWAS panels, but is still out of reach for large epidemiologic studies and the millions of rare variants expected poses challenges for distinguishing causal from non-causal variants. We review two types of designs for sequencing studies: two-phase designs for targeted follow-up of genomewide association studies using unrelated individuals; and family-based designs exploiting co-segregation for prioritizing variants and genes.Two-phase designs subsample subjects for sequencing from a larger case-control study jointly on the basis of their disease and carrier status; the discovered variants are then tested for association in the parent study. The analysis combines the full sequence data from the substudy with the more limited SNP data from the main study. We discuss various methods for selecting this subset of variants and describe the expected yield of true positive associations in the context of an on-going study of second breast cancers following radiotherapy.While the sharing of variants within families means that family-based designs are less efficient for discovery than sequencing unrelated individuals, the ability to exploit co-segregation of variants with disease within families helps distinguish causal from non-causal ones. Furthermore, by enriching for family history, the yield of causal variants can be improved and use of identity-by-descent information improves imputation of genotypes for other family members. We compare the relative efficiency of these designs with those using unrelated individuals for discovering and prioritizing variants or genes for testing association in larger studies. While associations can be tested with single variants, power is low for rare ones. Recent generalizations of burden or kernel tests for gene-level associations to family-based data are appealing. These approaches are illustrated in the context of a family-based study of colorectal cancer.

Genetic variation in the expression of human XMETs leads to inter-individual variability in metabolism of therapeutic agents as well as differed susceptibility to various diseases. Recent eQTL (expression quantitative traits loci) mapping in a few human cells/tissues have identified a number of SNPs significantly associated with mRNA expression of many XMET genes. These eQTLs are therefore important candidate markers for pharmacogenetic studies. However, questions remain about whether these SNPs are causative and in what mechanism these SNPs may function. Given the important role of microRNAs in gene transcription regulation, we hypothesize that those eQTLs or their proxies in strong linkage disequilibrium (LD) altering microRNA targeting are likely causative SNPs affecting gene expression. The aim of this study is to identify eQTLs potentially regulating major XMETs via interference with microRNA targeting. To this end, we performed a genome-wide screening for eQTLs for 409 genes encoding major drug metabolism enzymes transporters and transcription factors, in publically available eQTL datasets generated from the HapMap lymphoblastoid cell lines (LCLs) and human liver and brain tissue. As a result, 308 eQTLs significantly (p

Objective: Antiplatelet and/or anticoagulant therapy are commonly prescribed after fenestrated/branched endovascular aortic repair (F/BEVAR). However, the optimal regimen remains unknown. We sought to characterize practice patterns and outcomes of antiplatelet and anticoagulant use in patients who underwent F/BEVAR., Methods: Consecutive patients enrolled (2012-2023) as part of the United States Aortic Research Consortium (US-ARC) from 10 independent physician-sponsored investigational device exemption studies were evaluated. The cohort was characterized by medication regimen on discharge from index F/BEVAR: (1) Aspirin alone OR P2Y12 alone (single-antiplatelet therapy [SAPT]); (2) Anticoagulant alone; (3) Aspirin + P2Y12 (dual-antiplatelet therapy [DAPT]); (4) Aspirin + anticoagulant OR P2Y12 + anticoagulant (SAPT + anticoagulant); (5) Aspirin + P2Y12 + anticoagulant (triple therapy [TT]); and (6) No therapy. Kaplan-Meier analysis and Cox proportional hazards modeling were used to compare 1-year outcomes including survival, target artery patency, freedom from bleeding complication, freedom from all reinterventions, and freedom from stent-specific reintervention., Results: Of the 1525 patients with complete exposure and outcome data, 49.6% were discharged on DAPT, 28.8% on SAPT, 13.6% on SAPT + anticoagulant, 3.2% on TT, 2.6% on anticoagulant alone, and 2.2% on no therapy. Discharge medication regimen was not associated with differences in 1-year survival, bleeding complications, composite reintervention rate, or stent-specific reintervention rate. However, there was a significant difference in 1-year target artery patency. On multivariable analysis comparing with SAPT, DAPT conferred a lower hazard of loss of target artery patency (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27-0.84; P = .01). On sub-analyses of renal stents alone or visceral stents alone, DAPT no longer had a significantly lower hazard of loss of target artery patency (renal: HR, 0.66; 95% CI, 0.35-1.27; P = .22; visceral: HR, 0.31; 95% CI, 0.05-1.9; P = .21). Lastly, duration of DAPT therapy (1 month, 6 months, or 1 year) did not significantly affect target artery patency., Conclusions: Practice patterns for antiplatelet and anticoagulant regimens after F/BEVAR vary widely across the US-ARC. There were no differences in bleeding complications, survival or reintervention rates among different regimens, but higher branch vessel patency was noted in the DAPT cohort. These data suggest there is a benefit in DAPT therapy. However, the generalizability of this finding is limited by the retrospective nature of this data, and the clinical significance of this finding is unclear, as there is no difference in survival, bleeding, or reintervention rates amongst the different regimens. Hence, an "optimal" regimen, including the duration of such regimen, could not be clearly discerned. This suggests equipoise for a randomized trial, nested within this cohort, to identify the most effective antiplatelet/anticoagulant regimen for the growing number of patients being treated globally with F/BEVAR., Competing Interests: Disclosures A.S. reports consultant for Artivion, Cook Medical, and Philips; and receives research support from Cook Medical and Philips. All proceeds go to the UMass Memorial Hospital Foundation. A.W.B. reports onsultant for Artivion, Cook Medical, Medtronic, Philips, and Terumo Aortic; and receives research support from Cook Medical, Endospan, Medtronic, Philips, Terumo Aortic, and W.L. Gore & Associates. All proceeds go to the University of Alabama at Birmingham. M.A.F. reports consultant for WL Gore, Cook Medical, ViTAA, Centerline Biomedical, and Getinge; and receives research support from Cook Medical, WL Gore ViTAA, and Centerline Biomedical. W.A.L. reports consultant for Terumo Aortic. G.S.O. reports consultant for Cook, Centerline Biomedical, GE Healthcare, and Gore; and receives research support from GE Healthcare. F.E.P. reports stock options from Centerline Biomedical; and receives research support from Cook Medical. D.B.S. reports consultant for WL Gore, Cook Medical, Medtronic, and Philips; and receives research support from Cook Medical, Philips, and W.L. Gore. C.H.T. reports consultant for Cook Medical, WL Gore, and Philips; and receives research support from Cook Medical, Philips, and WL Gore., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Peripheral artery disease (PAD) is associated with worse survival following abdominal aortic aneurysm (AAA) repair. However, little is known about the impact of PAD and sex on outcomes following open infrarenal AAA repair (OAR)., Methods: All elective open infrarenal AAA cases were queried from the Society for Vascular Surgery Vascular Quality Initiative from 2003 to 2022. PAD was defined as history of non-cardiac arterial bypass, non-coronary percutaneous vascular intervention (PVI), or non-traumatic major amputation. Cohorts were stratified by sex and history of PAD. Multivariable logistic regression and Cox proportional hazards models were constructed to assess the primary endpoints: 30-day and 5-year mortality, respectively., Results: Of 4910 patients who underwent elective OAR, 3421 (69.7%) were men without PAD, 298 (6.1%) were men with PAD, 1098 (22.4%) were women without PAD, and 93 (1.9%) were women with PAD. Men with PAD had prior bypass (45%), PVI (62%), and amputation (6.7%). Women with PAD had prior bypass (32%), PVI (76%), and amputation (5.4%). Thirty-day mortality was significantly higher in men with PAD compared with men without PAD (4.4% vs 1.7%; P = .001) and in women with PAD compared with women without PAD (7.5% vs 2.4%; P = .01). After risk adjustment, when compared with men without PAD, women with PAD had nearly four times the odds of 30-day mortality (odds ratio, 3.86; 95% confidence interval [CI], 1.55-9.64; P = .004) and men with PAD had almost three times the odds of 30-day mortality (odds ratio, 2.77; 95% CI, 1.42-5.40; P = .003). Five-year survival was 87.8% in men without PAD, 77.8% in men with PAD, 85% in women without PAD, and 76.2% in women with PAD (P < .001). After risk adjustment, only men with PAD had an increased hazard of death at 5 years (hazard ratio, 1.52; 95% CI, 1.07-2.17; P = .019) compared with men without PAD., Conclusions: PAD is a potent risk factor for increased perioperative mortality in both men and women following OAR. In women, this equates to nearly four times the odds of perioperative mortality compared with men without PAD. Future study evaluating risk/benefit is needed to determine if women with PAD reflect a high-risk cohort that may benefit from a more conservative OAR threshold for treatment., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Although the Society for Vascular Surgery recommends repair of abdominal aortic aneurysms (AAA) at 5.5 cm or greater in men and 5.0 cm or greater in women, AAA repair below these thresholds has been well-documented. There are clear indications for repair other than these strict size criteria, but the expected proportion of such repairs in one's practice has not been studied. We sought to characterize the indications for repairs of aneurysms below diameter recommendations at a single academic center. Using the assumption that this real-world experience would approximate that of other practices, we then used national data to extrapolate these findings., Methods: A single-center retrospective review was conducted of all elective open AAA (oAAA) and endovascular aneurysm repair (EVAR) from 2010 to 2020 to assess the incidence of and indications for repair of aneurysms below diameter recommendations (defined as <5.5 cm in men and <5.0 cm in women). Reasons for these repairs were defined as (1) iliac aneurysm, (2) saccular morphology, (3) rapid expansion, (4) patient anxiety, (5) distal embolization, (6) other, and (7) no documented reason. The Vascular Quality Initiative (VQI) was queried for all asymptomatic oAAA and EVAR (2010-2020) and repairs below diameter recommendations were identified. Findings from the single-center analysis were applied to the VQI cohort to extrapolate estimates of reasons for repairs done nationally. In-hospital mortality and major adverse cardiac events (MACE) were compared between those below size recommendations and those meeting size recommendations., Results: Of 456 elective AAA repairs at our center, 147 (32%) were below size recommendations. This finding was more common for EVAR (35% vs 28%). Reasons were: not documented (41%), iliac aneurysm (23%), saccular (10%), rapid expansion (10%), patient anxiety (7%), other (6%), and distal embolism (3%). Of 44,820 elective AAA repairs in the VQI, 17,057 (38%) were below size recommendations (40% EVAR, 26% oAAA). Patients who were repaired below size recommendations had lower in-hospital death (oAAA, 2.4% vs 4.6% [P < .0001]; EVAR, 0.3% vs 0.8% [P < .0001]). When single-center findings were applied to the VQI dataset, an estimated 10,064 repairs were performed nationally for acceptable indications other than size criteria. Conversely, there may have been 6993 repairs (with an associated 35 deaths) performed without documented indication., Conclusions: Repairs for AAA below the recommended diameter guidelines account for approximately one-third of all elective AAA procedures in both the VQI and our single-center experience. Assuming our practice is typical, nearly 60% of repairs below size recommendations meet the criteria for other clear reasons. The remaining 40% lack a documented reason, meaning that 13% of all elective AAA repairs were done for aneurysms below size recommendations without an acceptable indication. As awareness of overuse and underuse is heightened, these data help to estimate the expected proportion of repairs for less common pathologies. They also provide a potential baseline data point for efforts at decreasing overuse., (Published by Elsevier Inc.)

The ongoing COVID19 pandemic is having detrimental effects on the mental and emotional well-being of many adults and children. It is relevant therefore to explore the combination of personal strengths and attributes that can help an individual develop resilience to such stress. Little is known about how psychological strength assets such as social connectedness, grit, hope, life meaning, and life satisfaction are inter-related, and if certain factors play a central role. This study involved a sample of 1,405 school-aged children in Hong Kong (50% female) from seven schools that participated in an online survey of psychological strengths. Data were analyzed by constructing a psychological network that found strength factors are inter-connected, and that 'school connectedness' and 'agency thinking' are central to the network. The information gained can be of value in any schools that are planning to provide strength-based interventions to help students maintain their psychological well-being during and after the COVID-19 pandemic., Competing Interests: Conflict of interest All authors have approved the final article and declare that there is no conflict of interest to disclose., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Machine learning methods are a novel way to predict and rank donors' willingness to donate blood and to achieve precision recruitment, which can improve the recruitment efficiency and meet the challenge of blood shortage. We collected information about experienced blood donors via short message service (SMS) recruitment and developed 7 machine learning-based recruitment models using PyCharm-Python Environment and 13 features which were described as a method for ranking and predicting donors' intentions to donate blood with a floating number between 0 and 1. Performance of the prediction models was assessed by the Area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score in the full dataset, and by the accuracy in the four sub-datasets. The developed models were applied to prospective validations of recruiting experienced blood donors during two COVID-19 pandemics, while the routine method was used as a control. Overall, a total of 95,476 recruitments via SMS and their donation results were enrolled in our modelling study. The strongest predictor features for the donation of experienced donors were blood donation interval, age, and donation frequency. Among the seven baseline models, the eXtreme Gradient Boosting (XGBoost) and Support vector machine models (SVM) achieved the best performance: mean (95%CI) with the highest AUC: 0.809 (0.806-0.811), accuracy: 0.815 (0.812-0.818), precision: 0.840 (0.835-0.845), and F1 score of XGBoost: 0.843 (0.840-0.845) and recall of SVM: 0.991 (0.988-0.994). The hit rate of the XGBoost model alone and the combined XGBoost and SVM models were 1.25 and 1.80 times higher than that of the conventional method as a control in 2 recruitments respectively, and the hit rate of the high willingness to donate group was 1.96 times higher than that of the low willingness to donate group. Our results suggested that the machine learning models could predict and determine the experienced donors with a strong willingness to donate blood by a ranking score based on personalized donation data and demographical details, significantly improve the recruitment rate of blood donors and help blood agencies to maintain the blood supply in emergencies., (© 2022. The Author(s).)

Objective: Hemoglobin A1c (HbA1c) is used as a marker of glycemic control, but the role of HbA1c before lower extremity bypass (LEB) in patients with diabetes remains unclear. We sought to characterize patients with diabetes undergoing LEB with and without HbA1c monitoring and to determine if HbA1c monitoring practices correlate with better outcomes., Methods: The Vascular Quality Initiative was queried for all LEB in patients with diabetes (2010-2020). Patients with diabetes were characterized based on therapy: diet-controlled, noninsulin medication use, or insulin use. Glycemic control was characterized by preoperative HbA1c within 6 months of surgery: unknown control (no HbA1c), well-controlled (HbA1c <7%), poorly-controlled (HbA1c 7%-10%), and uncontrolled (HbA1c >10%). Centers with >5 LEB/y were stratified into terciles according to rate of HbA1c monitoring. The unadjusted associations between glycemic control and in-hospital major adverse limb events, major adverse cardiac events, and mortality were assessed with univariate methods. The independent association of center-level HbA1c monitoring with 5-year survival and 3-year amputation-free survival (AFS) was determined with Kaplan-Meier analyses and Cox regression modeling, adjusted for differences in patient characteristics and center volume., Results: Of 16,092 patients with diabetes undergoing LEB, 4055 (25%) did not have a documented HbA1c. Insulin use was less common in no A1c (48%) and well-controlled diabetes (39%) compared with poorly controlled (67%) and uncontrolled diabetes (78%) (P < .01). In univariate analyses, glycemic control was not associated with differences for in-hospital major adverse limb events, major adverse cardiac events, or mortality. Of 162 centers, HbA1c monitoring practices varied widely (range: 12.5%-100% of LEB). The 3-year AFS and 5-year survival were worse in the highest monitoring tercile vs the lowest (73.6% vs 77.3%, P < .01, 72.1% vs 77.5%, P < .01, respectively). On multivariable analyses, centers in the highest tercile of monitoring had the greatest hazard of AFS (hazard ratio: 1.21, 95% confidence interval: 1.1-1.3, P < .001) and overall mortality (hazard ratio: 1.19, 95% confidence interval: 1.1-1.3, P < 0.001), compared with the centers in the lowest tercile of monitoring., Conclusions: Patients with diabetes and no preoperative HbA1c monitoring do not have worse LEB outcomes compared with those with HbA1c monitoring. Preoperative HbA1c monitoring varies widely, suggesting broad differences in practice and documentation. Centers with the highest rates of monitoring demonstrated inferior outcomes, likely due to other confounding unmeasured variables. These findings indicate that HbA1c monitoring before LEB, unto itself, should not be used as a measure of surgical quality., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: When the integrated vascular surgery training pathway was introduced, training was comprised of nearly equal amounts of core general surgery and vascular surgery experience. However, specific requirements for case numbers or types were not defined. Over time, the time spent on core general surgery requirements has been reduced, most recently in 2018, from 24 to 18 months. We sought to determine trends in general surgery case volume and type over the past 10 years for vascular surgery residents., Methods: We conducted a retrospective review of the Accreditation Council for Graduate Medical Education case log data for integrated vascular surgery graduates from 2012-2018. We evaluated trends in mean numbers of cases, categorized as general surgery open (GS-open), general surgery laparoscopic (GS-laparoscopic), vascular surgery open (VS-open), and vascular surgery endovascular (VS-endo). Cases were also categorized by anatomic region as head/neck, thoracic, or abdominal., Results: The mean number of total head/neck, thoracic, or abdominal cases logged by graduating integrated vascular surgery trainees was 263.5. This total, as well as the proportion of general surgery cases (35%-38%, p = 0.99) has remained constant over time. The type of general surgery cases has changed significantly, with an upward trend in the mean number of GS-open cases and downward trend in mean GS-laparoscopic cases (GS-open p = 0.006, GS-laparoscopic p = 0.048). Among head/neck and thoracic subgroups, no significant changes were observed, while in the abdominal subgroup, there has been a significant increase in GS-open over time (p = 0.005). Additionally, the number of open vascular abdominal aortic cases has remained stable, with an average of 36.82 per graduating trainee per year., Conclusions: In the 10 years since the introduction of integrated vascular surgery programs, total case volume and proportion of general surgery cases have remained remarkably stable. The type of general surgery cases has shifted though, with a decrease in GS-laparoscopic cases, replaced primarily by open abdominal cases. These changes likely reflect integrated vascular residents actively seeking out these opportunities during their core rotations and a willingness by general surgery partners to provide these opportunities. At the program level, these data may help guide program directors' choices about the specific core rotations they incorporate into their curriculum. At the national level, this information may contribute to future discussions regarding the optimal number of core general surgery rotation requirements., (Published by Elsevier Inc.)

Objective To observe the possible mechanism of Biejiajian Pill (BP) in fighting a- gainst hepatic fibrosis of hepatic stellate cell T6 ( HSC-T6) by studying effect of BP containing serum on inhibiting proliferation and inducing apoptosis of HSC-T6. Methods Forty Wistar rats were randomly di- vided into the negative control group (NC) , the positive drug control group (P) , high, middle, and low dose groups (H, M, L) , 8 in each group. BP suspension was administered by gastrogavage to rats in Group H, M, L at 21. 87, 43. 75, and 87. 50 mg/mL, respectively. Rats in Group NC were administered with equal volume of normal saline. Rats in Group P were administered with 0. 01 mg/mL colchicine solu- tion by gastrogavage. Each rat received 2 mL corresponding solution, twice per day, with an interval of 12 h gastrogavage, a total of 7 successive times to prepare drug containing serum. HSC-T6 cells were then randomly divided into drug containing serum groups (group H/M/L/NC) , colchicine positive control group (group P) , and the blank control group (BC). Cells in Group H/M/L/NC/P were fed with correspond- ing drug containing serums, while those in-Group BC were cultured with free drug serum. The proliferation inhibition rate of HSC-T6 was detected using CCK8 method at 24, 48, and 72 h, respectively. The apop- totic rate and cell cycle were detected using flow cytometry. Protein expressions of B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected using Western blot. Results Compared with Group NC, 24-h proliferation inhibition rate of HSC-T6 was obviously elevated in Group M, H, P (P < 0. 05). Compared with Group NC, 48- and 72-h proliferation inhibition rate of HSC-T6 was obviously ele- vated in Group L, M, H, P (P <0. 05). But there was no statistical difference in 24-, 48-, and 72-h prolif- eration inhibition rate of HSC-T6 among Group L, M, H, P (P >0. 05). Compared with Group NC and BC, early-and late-stage apoptosis rates of HSC-T6 obviously increased in Group M, H, P (P<0. 05) ; G,/G1 phase cell number obviously increased in Group M, H, P (P <0. 05) ; S phase and G2/M phase cell num- bers obviously decreased in Group L, M, H, P (P <0. 05). There was no statistical difference in Bcl-2 protein expression among each group (P>0. 05). Compared with Group NC, Bax protein expression ob- viously increased Group L, M, H, P (P <0. 01). Conclusion The mechanism of BP for fighting against hepatic fibrosis might be associated with inhibiting proliferation of HSC-T6 and inducing apoptosis.

Brachymystax tsinlingensis Li, 1966 is revalidated and redescribed. It can be distinguished from all congeners by the following combination of characteristics: no spots on operculum; gill rakers 15-20; lateral-line scales 98-116; pyloric caeca 60-71. Unique morphological characters and genetic divergence of this species are discussed. This species has a limited distribution in several streams of the middle part of the Qinling Mountains in China. Methods for management and protection of B. tsinlingensis need to be re-evaluated.

Background: Although periodic blood shortages are widespread in major Chinese cities, approximately 1 x 10(5) U of whole blood are discarded yearly because of under-collection. To reduce the wastage of acid citrate dextrose solution B (ACD-B) anticoagulated under-collected whole blood (UC-WB), this study was performed to elucidate the effect of extracellular pH and holding time on erythrocyte quality. Mannitol-adenine-phosphate (MAP) erythrocyte concentrates (UC-RBCs) were prepared with UC-WB to assess the safety and efficacy of this component., Methods: The effect of the different extracellular pH levels and storage times on erythrocytes was assessed by fluorescent probes, SDS-PAGE electrophoresis, electron microscopy and spectroscopy. In vitro properties of 34 UC-RBCs that were prepared with UC-WB at different times after collection were analyzed and compared to normal RBCs during 35 days of storage. The results of transfusion with UC-RBCs and the incidence of adverse reactions in 49 patients were determined., Results: 1) Low extracellular pH levels and long storage time induced increases in RBC fluorescence polarization and mean microviscosity, changes in membrane fluidity, band 1, 2 and 3 protein expression, and erythrocyte morphology. 2) During storage for 35 days, difference in between-subjects effects of K+, hemolysis and supernatant erythrocyte membrane protein (EMP) were statistically significant (P = 0.041, 0.007 and 0.002, respectively), while the differences between these parameters in the 4 h group and comparable controls were less significant. 3) Clinical data from 49 patients confirmed that transfusions with UC-RBCs were satisfactory with no adverse reactions., Conclusion: These results suggest that it is feasible to prepare RBCs with ACD-B anticoagulated UC-WB at a minimum of 66% volume of the labeled collection. It was effective and safe to transfuse the UC-RBCs prepared within 4 h after collection and stored within 7 days. The use of UC-WB would be a welcome addition to limited blood resources in China., Trial Registration: Chinese Clinical Trial Registry ChiCTR-TRC-13003967.

The hallmarks of Alzheimer's disease (AD) are the aggregates of amyloid-β (Aβ) peptides and tau protein. Autophagy is a major cellular pathway leading to the removal of aggregated proteins. We have reported recently that autophagy was responsible for amyloid precursor protein cleaved C-terminal fragment (APP-CTF) degradation and amyloid β clearance in an Atg5-dependent manner. Here we aimed to elucidate the molecular mechanism by which autophagy mediates the degradation of APP-CTF and the clearance of amyloid β. Through affinity purification followed by mass spectrum analysis, we identified adaptor protein (AP) 2 together with phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) as binding proteins of microtubule-associated protein 1 light chain 3 (LC3). Further analysis showed that AP2 regulated the cellular levels of APP-CTF. Knockdown of AP2 reduced autophagy-mediated APP-CTF degradation. Immunoprecipitation and live imaging analysis demonstrated that AP2 and PICALM cross-link LC3 with APP-CTF. These data suggest that the AP-2/PICALM complex functions as an autophagic cargo receptor for the recognition and shipment of APP-CTF from the endocytic pathway to the LC3-marked autophagic degradation pathway. This molecular mechanism linking AP2/PICALM and AD is consistent with genetic evidence indicating a role for PICALM as a risk factor for AD.

Disruption of fast axonal transport (FAT) is an early pathological event in Alzheimer's disease (AD). Soluble amyloid-β oligomers (AβOs), increasingly recognized as proximal neurotoxins in AD, impair organelle transport in cultured neurons and transgenic mouse models. AβOs also stimulate hyperphosphorylation of the axonal microtubule-associated protein, tau. However, the role of tau in FAT disruption is controversial. Here we show that AβOs reduce vesicular transport of brain-derived neurotrophic factor (BDNF) in hippocampal neurons from both wild-type and tau-knockout mice, indicating that tau is not required for transport disruption. FAT inhibition is not accompanied by microtubule destabilization or neuronal death. Significantly, inhibition of calcineurin (CaN), a calcium-dependent phosphatase implicated in AD pathogenesis, rescues BDNF transport. Moreover, inhibition of protein phosphatase 1 and glycogen synthase kinase 3β, downstream targets of CaN, prevents BDNF transport defects induced by AβOs. We further show that AβOs induce CaN activation through nonexcitotoxic calcium signaling. Results implicate CaN in FAT regulation and demonstrate that tau is not required for AβO-induced BDNF transport disruption.

We reviewed the taxonomy and systematics research history of freshwater fish in China based on 1 236 taxonomic literature records on Chinese freshwater fish. The research was divided into five research periods according to specific historical events: (1) period by foreign scholars, (2) period with Chinese scholars, (3) period during World War II and Civil War, (4) recovery period and (5) period of rapid development. There were representative studies and innovations in all periods. We also discuss here the characteristics of each period on the basis of literature analysis.

Background: The β-amyloid peptide (Aβ) contains a Gly-XXX-Gly-XXX-Gly motif in its C-terminal region that has been proposed to form a "glycine zipper" that drives the formation of toxic Aβ oligomers. We have tested this hypothesis by examining the toxicity of Aβ variants containing substitutions in this motif using a neuronal cell line, primary neurons, and a transgenic C. elegans model., Results: We found that a Gly37Leu substitution dramatically reduced Aβ toxicity in all models tested, as measured by cell dysfunction, cell death, synaptic alteration, or tau phosphorylation. We also demonstrated in multiple models that Aβ Gly37Leu is actually anti-toxic, thereby supporting the hypothesis that interference with glycine zipper formation blocks assembly of toxic Aβ oligomers. To test this model rigorously, we engineered second site substitutions in Aβ predicted by the glycine zipper model to compensate for the Gly37Leu substitution and expressed these in C. elegans. We show that these second site substitutions restore in vivo Aβtoxicity, further supporting the glycine zipper model., Conclusions: Our structure/function studies support the view that the glycine zipper motif present in the C-terminal portion of Aβ plays an important role in the formation of toxic Aβ oligomers. Compounds designed to interfere specifically with formation of the glycine zipper could have therapeutic potential.