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To compare the outcomes of patients requiring extracorporeal membrane oxygenation (ECMO) support who had a restrictive transfusion strategy with those who had a liberal strategy.We retrospectively reviewed all adult patients from 2010 to 2019 who received a minimum of one packed red blood cell (pRBC) during ECMO. Hemoglobin values before each transfusion were retrieved. Restrictive transfusion strategy was defined as a transfusion threshold ≤8.5 g/dl in all transfusion episodes for a single patient, while liberal transfusion strategy was defined as a transfusion threshold8.5 g/dl in any transfusion episode.The analysis included 763 patients, with 138 (18.1%) patients in the restrictive and 625 (81.9%) in the liberal transfusion strategy group. The median hemoglobin level, taking into account all measured hemoglobin values, during ECMO support was 8.3 and 9.9 g/dl, and the average units of pRBC received per day were 0.7 (0.3-1.8) and 1.2 (0.6-2.3), respectively. There were no significant differences in intensive care unit (ICU) mortality (adjusted odds ratio (OR), 0.86; 95% CI 0.56-1.30; p = .47), hospital mortality (adjusted OR, 0.79; 95% CI 0.52-1.21; p = .28), and 90-day mortality (adjusted OR, 0.84; 95% CI 0.55-1.28; p = .42) between the two groups. Among subgroup analyses, a restrictive transfusion strategy was associated with decreased risk of ICU mortality in patients on veno-venous ECMO (adjusted OR, 0.36; 95% CI 0.17-0.73; p = .005). There was no heterogeneity on outcomes across patients stratified by age, APACHE IV score, or need for large volume transfusion.Our data suggested it may be safe to adopt a restrictive red cell transfusion threshold of 8.5 g/dl in patients on ECMO, and highlighted the need for prospective trials in this heavily-transfused population.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V-A ECMO during the acute and delayed stages of acute myocardial dysfunction.A total of 46 adult patients who were supported by peripheral V-A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1 ± 1 of V-A ECMO initiation (n = 45, 'acute phase') and mean day 4 ± 2 of V-A ECMO initiation (n = 36, 'delayed phase'). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from -6.1 (-8.9 to -4.0)% during 120% TBF to -8.8 (-11.5 to -6.0)% during 50% TBF (P 0.001). The sensitivity of LV GLS to changes in ECMO flow was significantly greater in the acute phase of myocardial injury compared with the delayed phase [median (IQR) percentage change: 72.7 (26.8-100.0)% vs. 22.5 (14.9-43.8)%, P 0.001]. Findings from other echocardiographic parameters including LV ejection fraction [43.0 (29.1-56.8)% vs. 22.8 (9.2-42.2)%, P = 0.012] and LV outflow tract velocity-time integral [45.8 (18.6-58.7)% vs. 24.2 (12.6-34.0)%, P = 0.001] were similar. A total of 24 (52.2%) patients were weaned off ECMO successfully.We demonstrated that LV systolic function was significantly more sensitive to the afterload effects of V-A ECMO during the acute stage of myocardial dysfunction compared with the delayed phase. Understanding the evolution of the heart-ECMO interaction over the course of acute myocardial dysfunction informs the clinical utility of echocardiographic assessment in patients on V-A ECMO.

It is important to quantify the amount of crossover innervation from the anterior interosseous nerve (AIN) through Martin-Gruber anastomosis (MGA) particularly in patients with high ulnar nerve injury who undergo nerve transfer surgery. The objective of this study is to describe a novel electrophysiological method for quantifying innervation from the AIN that can be done using conventional nerve conduction study setup and commonly available software for analysis.Seven subjects with MGA and nine patients who had undergone AIN to ulnar nerve transfer underwent conventional motor nerve conduction studies. Recording was done over the hypothenar and first dorsal interosseous muscles while stimulating the median and ulnar nerves at the wrist and elbow. Datapoint-by-datapoint subtraction of the compound muscle action potentials evoked at the elbow and wrist was performed after they had been onset-aligned. The results were compared to the collision technique and innervation ratio method.Results from the digital subtraction method were highly correlated with the collision technique (r = 0.96, p 0.05). In contrast, its correlation with the innervation ratio method is substantially lower.In comparison to previously described techniques, the digital subtraction method has a number of practical advantages. It uses conventional nerve conduction study setup, and the added step of digital alignment and subtraction can be done through commonly available software. With the increasing use of nerve transfer surgery in severe high ulnar nerve injury, this could be a useful method to identify the presence of MGA prior to surgery and for evaluating nerve recovery following surgery.

Telomerase reverse transcriptase (TERT) promoter (pTERT) mutation has often been described as a late event in gliomagenesis and it has been suggested as a prognostic biomarker in gliomas other than 1p19q codeleted tumors. However, the characteristics of isocitrate dehydrogenase (IDH) wild type (wt) (IDHwt), pTERTwt glioblastomas are not well known. We recruited 72 adult IDHwt, pTERTwt glioblastomas and performed methylation profiling, targeted sequencing, and fluorescence in situ hybridization (FISH) for TERT structural rearrangement and ALT (alternative lengthening of telomeres). There was no significant difference in overall survival (OS) between our cohort and a the Cancer Genome Atlas (TCGA) cohort of IDHwt, pTERT mutant (mut) glioblastomas, suggesting that pTERT mutation on its own is not a prognostic factor among IDHwt glioblastomas. Epigenetically, the tumors clustered into classic-like (11%), mesenchymal-like (32%), and LGm6-glioblastoma (GBM) (57%), the latter far exceeding the corresponding proportion seen in the TCGA cohort of IDHwt, pTERTmut glioblastomas. LGm6-GBM-clustered tumors were enriched for platelet derived growth factor receptor alpha (PDGFRA) amplification or mutation (p = 0.008), and contained far fewer epidermal growth factor receptor (EGFR) amplification (p 0.01), 10p loss (p = 0.001) and 10q loss (p 0.001) compared with cases not clustered to this group. LGm6-GBM cases predominantly showed ALT (p = 0.038). In the whole cohort, only 35% cases showed EGFR amplification and no case showed combined chromosome +7/-10. Since the cases were already pTERTwt, so the three molecular properties of EGFR amplification, +7/-10, and pTERT mutation may not cover all IDHwt glioblastomas. Instead, EGFR and PDGFRA amplifications covered 67% and together with their mutations covered 71% of cases of this cohort. Homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A)/B was associated with a worse OS (p = 0.031) and was an independent prognosticator in multivariate analysis (p = 0.032). In conclusion, adult IDHwt, pTERTwt glioblastomas show epigenetic clustering different from IDHwt, pTERTmut glioblastomas, and IDHwt glioblastomas which are pTERTwt may however not show EGFR amplification or +7/-10 in a significant proportion of cases. CDKN2A/B deletion is a poor prognostic biomarker in this group.

LRWD1, also known as ORCA, is a nuclear protein functioning in multiple biological processes. Using its WD40 domain LRWD1 interacts with repressive histone marks and maintains the silencing of heterochromatin regions in mammalian cells. ORCA also associates with the origin recognition complex (ORC) and facilitates prereplication complex formation at late-replicating origins. However, whether LRWD1 plays a role during development and the functional significance of LRWD1 in vivo remains largely unknown. Using gene-trap approach we generated Lrwd1 knockout mice and examined the expression of Lrwd1 during embryonic development. We found that Lrwd1 is ubiquitously expressed in the majority of the developing mouse embryo. Depletion of LRWD1 did not affect embryonic development but the postnatal growth of the homozygous mutants is retarded. In vitro cultured mouse embryonic fibroblasts (MEFs) depleted of LRWD1 displayed a reduced proliferation compared to wild type cells. We also showed that the knockout of Lrwd1 in MEFs increased the expression of the epigenetically silenced repetitive elements but with minimal effect on the expression of protein coding genes. Together, these results suggest that LRWD1 plays an important, but not essential, role in postnatal development by regulating cell proliferation likely through modulating DNA replication.

We aimed to characterise glioblastomas of adolescents and young adults (AYAs) that were isocitrate dehydrogenase (IDH) wild type (wt) and H3wt.Fifty such patients (aged 16-32) were studied by methylation profiling, targeted sequencing and targeted RNA-seq.Tumours predominantly clustered into three methylation classes according to the terminology of Capper et al. (2018): (anaplastic) pleomorphic xanthoastrocytoma (PXA) (21 cases), GBM_midline (15 cases) and glioblastoma RTK/mesenchymal (seven cases). Two cases clustered with ANA_PA, four cases with LGG classes and one with GBM_MYCN. Only fifteen cases reached a calibrated score0.84 when the cases were uploaded to DKFZ Classifier. GBM_midline-clustered tumours had a poorer overall survival (OS) compared with the PXA-clustered tumours (p = 0.030). LGG-clustered cases had a significantly better survival than GBM_midline-clustered tumours and glioblastoma RTK/mesenchymal-clustered tumours. Only 13/21 (62%) of PXA-clustered cases were BRAF V600E mutated. Most GBM_midline-clustered cases were not located in the midline. GBM_midline-clustered cases were characterised by PDGFRA amplification/mutation (73.3%), mutations of mismatch repair genes (40.0%), and all showed H3K27me3 and EZH1P loss, and an unmethylated MGMT promoter. Across the whole cohort, MGMT promoter methylation and wt TERT promoter were favourable prognosticators. Mismatch repair gene mutations were poor prognosticators and together with methylation class and MGMT methylation, maintained their significance in multivariate analyses. BRAF mutation was a good prognosticator in the PXA-clustered tumours.Methylation profiling is a useful tool in the diagnosis and prognostication of AYA glioblastomas, and the methylation classes have distinct molecular characteristics. The usual molecular diagnostic criteria for adult IDHwt glioblastoma should be applied with caution within the AYA age group.

BACKGROUND AND OBJECTIVES Precise prognostic prediction for an individual hepatocellular carcinoma (HCC) patient before and after liver resection is important. We aimed to establish simple prognostic models to predict disease-free survival (DFS) for these patients. METHODS Six hundred and ninety-eight HCC patients with liver resections were reviewed. Preoperative (model 1) and postoperative (model 2) nomogram-based scoring systems were constructed by multivariate analyses, and DFS was estimated. RESULTS Among 698 patients, 490 (70.2%) patients had tumor recurrence at a median follow-up of 84.4 months. Risk factors of tumor recurrence in model 1 included viral hepatitis, platelet count, albumin, indocyanine green retention rate, multiplicity of tumor, and radiologic total tumor volume (TTV). Prognostic variables identified in model 2 were viral hepatitis, platelet count, multiplicity of tumor, cirrhosis, microvascular invasion, and pathologic TTV. By nomogram in model 1, the patients were classified into three groups with 5-year DFS of 61.0%, 35.7%, and 21.1%, respectively (P

Alternating therapeutic plasma exchange with double plasma molecular adsorption system can rapidly remove bilirubin and ammonia and supplement the essential substance from the blood, which could be used as an effective treatment for fulminant hepatic failure., Alternating TPE with DPMAS could remove bilirubin and ammonia, which may partially replace liver function and provide transition time for FHF patients waiting for liver transplantation.

Background Hepatocellular carcinoma ranks fourth in cancer‐related mortality currently lacks effective therapeutics. Fucoidan is sulfated polysaccharide that is mainly found in brown seaweeds. In this study, we investigated the effects and mechanisms of low molecular weight fucoidan (i.e. oligo‐fucoidan [OF]) preventing hepatocarcinogenesis. Methods We used [HBx,src], [HBx,src,p53−/+], and [CD36] transgenic zebrafish liver cancer model treated with OF, and performed molecular and histopathological analysis. Transcriptomic and pathways analysis was performed. Results Decreased expression of lipogenic enzymes, fibrosis markers, and cell cycle/proliferation markers by OF in [HBx,src] and [HBx,src,p53−/+] transgenic fish. Liver fibrosis was decreased as revealed by Sirius Red staining, and the liver cancer formation was eventually reduced by feeding OF. OF was also found to be capable of reducing lipid accumulation and cancer formation in non‐B non‐C Hepatocellular carcinoma (HCC) model in CD36 transgenic zebrafish. Whole‐genome expression analysis showed that 661 genes were up‐regulated, and 451 genes were downregulated by feeding OF. Upregulated genes were mostly found in protein transporter activity, and downregulated genes were enriched with response to extracellular stimulus and metal binding in gene ontology analysis. The driver gene was HNF4A revealed by NetworkAnalyst from OF differential regulated genes at various insults. OF is able to bind the asialoglycoprotein receptor (ASGR) in hepatoma cells, and increased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in both hepatoma cells and [HBx,src,p53−/+] transgenic fish liver cancer model. Using chromatin‐immunoprecipitation, we found pSTAT3 could associate with the P1 promoter of HNF4A. Knockdown of either ASGR or HNF4A reversed OF mediated anti‐cancer cell proliferation. Conclusions Taken together, we provide evidence that OF exhibits the anti‐HCC, anti‐steatosis, and anti‐fibrosis effect for liver in zebrafish models, and the anti‐cancer potential of OF attributed to the binding to ASGR and activation of STAT3/HNF4A signaling. OF might be potentially valuable for the management of HCC., We used zebrafish preclinical model and whole‐genome transcriptome analysis to understand the mechanisms for oligo‐fucoidan anti‐HCC effect.Oligo‐fucoidan binds to ASGR receptor on hepatocyte.Oligo‐fucoidan activates the phosphorylation of STAT3, which binds to the P1 promoter of HNF4A, transcriptionally regulates P1‐isoform HNF4A expression.Oligo‐fucoidan prevents steatosis, fibrosis and HCC formation in HBx,src,p53−/+, diet induced obesity and CD36 transgenic fish.

Tendinopathy includes cases with chronic tendon pain and spontaneous tendon ruptures, which is putatively resulted from failed tendon healing. Overuse is a major risk factor of tendinopathy, which can impose mechanical and oxidative stress to tendons. Previous studies investigated the influences of mechanical stress, but the direct impact of oxidative stress on tendon healing remains unclear. We hypothesized that imposed oxidative stress can impair tendon healing and lead to tendinopathic changes. Thirty-nine rats were operated for patellar tendon window injury. From weeks 3-5 post-operation, the rats received three weekly subcutaneous injections of saline, 50 or 500 μM H2 O2 (n = 13) over patellar tendon. Gait analysis for pain assessment and 3D ultrasound imaging for detection of tendinopathic changes were performed at pre-injury and 6-week post-operation. At week 6, knee specimens were harvested for histology or tensile mechanical test. Elastic modulus of the healing patellar tendons was significantly lower in 50 μM but not 500 μM H2 O2 group, while ultimate mechanical stress was not significantly different across groups. Similarly, only the 50 μM H2 O2 group exhibited pain-associated gait asymmetry. Significant tendon swelling with increased tendon volume was observed in the 50 μM H2 O2 group. There were hypoechogenic changes in the tendon wound, but there was no significant difference in percentage vascularity. H2 O2 impaired tendon healing and elicited tendinopathic changes, with respect to pain and structural abnormalities. Oxidative stress plays a role in the failed tendon healing of tendinopathies, and H2 O2 -induced failed tendon healing may serve as a good animal model to study tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3268-3274, 2018.

By altering the intrinsic metabolism of the cell, including the upregulation of regeneration-associated genes (RAGs) and the production of structural proteins for axonal outgrowth, the conditioning lesion sets up an environment highly conducive to regeneration. In this review, we assess 40 years of research to provide a comprehensive overview of the conditioning lesion literature, directed at (1) discussing the mechanisms of and barriers to nerve regeneration that can be mitigated by the conditioning lesion, (2) describing the cellular and molecular pathways implicated in the conditioning lesion effect, and (3) deliberating on how these insights might be applied clinically. The consequential impact on regeneration is profound, with a conditioned nerve demonstrating longer neurite extensions in vitro, enhanced expression of RAGs within the dorsal root ganglia, early assembly and transportation of cytoskeletal elements, accelerated axonal growth, and improved functional recovery in vivo. Although this promising technique is not yet feasible to be performed in humans, there are potential strategies, such as conditioning electrical stimulation that may be explored to allow nerve conditioning in a clinically safe and well-tolerated manner. Ann Neurol 2018;83:691-702.

Indications of liver transplantation are extensive, but deceased donation does not meet the demand. Hepatitis B surface antigen (HBsAg)-positive grafts used to be discarded in the past. The aim of this study was to examine viral activity and outcome of HBsAg-positive deceased grafts transplanted to HBsAg-positive recipients. Eleven HBsAg-positive deceased grafts were transplanted to HBsAg-positive patients with acute liver failure (3 patients), hepatocellular carcinoma (6 patients) and repeatedly bleeding varices (2 patients). Postoperatively, hepatitis B virus (HBV) infection was treated by a combination of antiviral nucleoside and nucleotide analogues. HBV DNA and HBsAg were measured periodically. The median (interquartile) model of end-stage liver disease score for the recipients was 19 (16-32) with a range from 11 to 40. HBV DNA was detected in 6 patients with a range from 61 to 1083 IU/mL before transplantation. After transplantation, HBV DNA was detected in 4 patients in the first month and 2 patients in the 6th month and became undetectable for all patients at end of the first year. The quantitative HBsAg ranged from 0.86 to 241.1 IU/mL at 6 months and 0.34 to 238.5 IU/mL at 24 months (P = .135). Three of the patients died in the early phase, and the other patients were followed up for 40.0 ± 19.2 months with normal liver function. In conclusion, HBsAg-positive deceased liver grafts function well with minimal viral activity under treatment of combined antiviral nucleoside and nucleotide analogues. Use of HBsAg-positive deceased grafts is feasible and increases the donor pool to rescue dying patients.

Aim Depressed skull fracture is a neurosurgical emergency. Surgical treatment usually requires a sizeable scalp incision and burr hole with or without craniotomy for reduction. However, depressed skull fracture in neonates, or ‘ping pong’ fracture, is an uncommon clinical condition, occurring in approximately 4–10 in 100 000 live births. No standard treatment is established for depressed skull fracture in neonates. With a minimally-invasive technique, a good surgical outcome can be achieved with minimal blood loss and no bone loss. Patients and Methods A full-term, neonatal girl presented with spontaneous ‘ping pong’ fracture after a smooth, normal vaginal delivery. The anterior fontanelle was full. Computed tomography of the brain showed right parietal depressed skull fracture with sulci effacement, obliteration of the lateral ventricle and midline shift. Skull fracture reduction was performed with the bone elevation technique via access to the coronal suture without a burr hole or craniotomy. Results A small stab wound incision was made over the right coronal suture at the lateral edge of the anterior fontanelle. This site was in close proximity to the anterior margin of the depressed skull fracture. With access to the coronal suture and dissection in the epidural space, reduction was achieved intraoperatively by elevation of the inner table of the skull bone. Blood loss was minimal, and there was no bone loss. The clinical outcome was excellent at 1-week, 3-months’, 1-year and 18-months’ follow up. Conclusion For neonatal depressed skull fractures with clinical and radiographic evidence of a mass effect requiring surgical intervention, elevation with no burr hole is a good technique for bone reduction with minimal blood loss and no bone loss.

BACKGROUND: Ankle foot orthoses (AFOs) are commonly prescribed to individuals with Charcot-Marie-Tooth disease (CMT). The aim of this study was to evaluate patient reported satisfaction with orthotic devices and services in individuals with CMT to provide preliminary data for advancing AFO development and improving clinical care. METHODS: The Orthotics and Prosthetics Users Survey was distributed via e-mail through the Inherited Neuropathy Consortium (INC) Contact Registry and includes 11 device-specific questions and 10 service-related questions. Participants were also asked open-ended questions about their experiences with AFOs. RESULTS: Three hundred and fourteen individuals completed the survey. Over one-third of participants provided negative responses, including dislike of AFO appearance, discomfort, abrasions or irritations, and pain. Ratings of orthotic services were generally positive. CONCLUSIONS: Lower scores related to discomfort, abrasions and pain identified areas for AFO improvement. Continued research in these areas will be beneficial to informing and advancing AFO development and improving clinical care.

A rhodium(III)-catalyzed cycloaddition of N-tert-butoxycarbonylhydrazones with internal alkynes was developed. The reaction features a regioselective α-imino alkyl C(sp3)−H bond functionalization resulting in selective formation of highly functionalized NH-free pyrroles. Our studies showed that utilizing the N-tert-butoxycarbonyl (N-Boc) as the oxidizing directing group is critical for achieving the observed pyrrole formation versus the isoquinoline formation. To account for the pyrrole formation, we hypothesized that a prior tautomerization of the N-Boc-hydrazones to enamines should occur, followed by regioselective C(sp2)–H cleavage to form a putative five-membered rhodacycle. Subsequent coupling of the rhodacycle with the alkynes would afford the pyrrole products.

Tendon injures are common orthopedic conditions, but tendon development and the pathogenesis of tendon injures, such as tendinopathy, remain largely unknown and have limited the development of clinical therapy. Studies on tenogenic differentiation at the molecular level may help in developing novel therapeutic strategies. As novel regulators, long noncoding RNAs (lncRNAs) have been found to have widespread biological functions, and emerging evidence demonstrates that lncRNAs may play important regulatory roles in cell differentiation and tissue regeneration. In this study, we found that lncRNA H19 stimulated tenogenesis of human tendon-derived stem cells. Stable overexpression of H19 significantly accelerated TGF-β1-induced tenogenic differentiation in vitro and accelerated tendon healing in a mouse tendon defect model. H19 directly targeted miR-29b-3p, which is considered to be a negative regulator of tenogenesis. Furthermore, miR-29b-3p directly suppressed the expression of TGF-β1 and type I collagen, thereby forming a novel regulatory feedback loop between H19 and TGF-β1 to mediate tenogenic differentiation. Our study demonstrated that H19 promotes tenogenic differentiation both in vitro and in vivo by targeting miR-29b-3p and activating TGF-β1 signaling. Regulation of the TGF-β1/H19/miR-29b-3p regulatory loop may be a new strategy for treating tendon injury.-Lu, Y.-F., Liu, Y., Fu, W.-M., Xu, J., Wang, B., Sun, Y.-X., Wu, T.-Y., Xu, L.-L, Chan, K.-M., Zhang, J.-F., Li, G. Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon healing through targeting miR-29b-3p and activating TGF-β1 signaling.

A series of full-scale laboratory experiments was conducted to investigate the cyclic behaviour of an external diaphragm joint between a steel I-beam and a circular hollow section column. The joint incorporated two diaphragm plates (DPs) welded to the column external wall and bolted to the flanges of the beam using tapered cover plates (TCPs). The joint was designed to limit yielding and plastic hinging to the TCPs whilst the other joint components remained elastic. This is for the joint to qualify for the use in structures classified in the Damage Control Structural Performance range according to FEMA-356. Two parameters related to the TCPs were investigated in this paper; steel grade and bolt preloading force. The use of higher steel grades was found to impose undesirable higher strain demands in the beam and DPs and dissipate less energy than the joints with the lower grade. A controlled reduction in the bolts preloading force allowed connection slippage to occur beyond the serviceability limit, created an additional energy dissipation fuse and allowed rotation of the plastic hinge region to exceed 25mrad required for medium ductility class structures.

Polydimethylsiloxane (PDMS)-grafted nanoparticles and PDMS were added, respectively, to inhibit the dewetting of polymer films and the formation of surface patterns in spin coating. Uniform and flat films were successfully achieved with the addition of PDMS-grafted silica nanoparticles or PDMS. Time-of-flight secondary ion mass spectrometry depth profiling indicated that PDMS-grafted silica nanoparticles and PDMS preferentially segregated to the surface. A high concentration of bromine end groups was observed at the interface. The surface layer of PDMS or PDMS-grafted silica nanoparticles can decrease the surface tension of the polymer solutions and reduce the evaporation rates of the solvents, providing more time for the bromine end groups to anchor themselves at the silicon substrates. Copyright © 2016 John Wiley & Sons, Ltd.

Diabetic retinopathy (DR) and age‐related macular degeneration (AMD) are two important leading causes of acquired blindness in developed countries. As accumulation of advanced glycation end products (AGEs) in retinal pigment epithelial (RPE) cells plays an important role in both DR and AMD, and the methylglyoxal (MGO) within the AGEs exerts irreversible effects on protein structure and function, it is crucial to understand the underlying mechanism of MGO‐induced RPE cell death. Using ARPE‐19 as the cell model, this study revealed that MGO induces RPE cell death through a caspase‐independent manner, which relying on reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) loss, intracellular calcium elevation and endoplasmic reticulum (ER) stress response. Suppression of ROS generation can reverse the MGO‐induced ROS production, MMP loss, intracellular calcium increase and cell death. Moreover, store‐operated calcium channel inhibitors MRS1845 and YM‐58483, but not the inositol 1,4,5‐trisphosphate (IP3) receptor inhibitor xestospongin C, can block MGO‐induced ROS production, MMP loss and sustained intracellular calcium increase in ARPE‐19 cells. Lastly, inhibition of ER stress by salubrinal and 4‐PBA can reduce the MGO‐induced intracellular events and cell death. Therefore, our data indicate that MGO can decrease RPE cell viability, resulting from the ER stress‐dependent intracellular ROS production, MMP loss and increased intracellular calcium increase. As MGO is one of the components of drusen in AMD and is the AGEs adduct in DR, this study could provide a valuable insight into the molecular pathogenesis and therapeutic intervention of AMD and DR.

Cirrhosis is the endpoint of liver fibrosis that is accompanied by limited regeneration capacity and complications and is the ultimate cause of death in many patients. Despite this, few studies have thoroughly looked at the gene expression profiles in the cirrhotic liver. Hence, this study aims to identify the genes that were differentially expressed in the cirrhotic liver and to explore the putative related signaling pathway and interaction networks. The gene expression profiles of cirrhotic livers and noncirrhotic livers were examined and compared using microarray gene analysis. Proteins encoded by the differentially expressed genes were analyzed for functional clustering and signaling pathway involvement using MetaCore bioinformatics analyses. The Gene Ontology analysis as well as the Kyoto encyclopedia of Genes and Genomes pathway analysis were also performed. A total of 213 significant genes were differentially expressed at more than a two-fold change in cirrhotic livers as compared to noncirrhotic livers. Of these, 105 upregulated genes and 63 downregulated genes were validated through MetaCore bioinformatics analyses. The signaling pathways and major functions of proteins encoded by these differentially expressed genes were further analyzed; results showed that the cirrhotic liver has a unique gene expression pattern related to inflammatory reaction, immune response, and cell growth, and is potentially cancer related. Our findings suggest that the microarray analysis may provide clues to the molecular mechanisms of liver cirrhosis for future experimental studies. However, further exploration of areas regarding therapeutic strategy might be possible to support metabolic activity, decrease inflammation, or enhance regeneration for liver cirrhosis.

Aim The aim of the present study was to assess patients' understanding of their informed consent to surgery preoperatively. Appropriate completeness of essential items in the written consent form was also verified. Patients and Methods An audit was conducted from March to May 2013 at a university teaching hospital. All participants were adult surgical patients. Operations were confined to major category on elective basis performed under general anaesthesia. The first part of the audit consisted of a structured questionnaire with five questions concerning their understanding and perception of the surgery. In the second part of the audit, the completeness of all fundamental items entered into the standardized written consent form was verified. Results A total of 100 surgical patients were studied, with a median age of 61 years (range: 22–89). A total of 99 per cent of participants could state the correct name and site of the procedure, and 92 per cent could state the mode of anaesthesia. Only 39 per cent of patients received an information leaflet regarding the operation, of which 80 per cent claimed this could enhance their understanding of the procedure. Only 70 per cent of them could recall the potential surgical risks. Most essential items were completed in the consent forms. Witnesses were involved only in 24 per cent of cases. Illegible surgeons' handwriting was observed in 6 per cent of consent documents. Conclusions Most patients could understand the nature and site of the operation they were going to receive. The provision of relevant information to our patients preoperatively was insufficient. Patients had limited recall of the potential surgical risks. There is room for improvement in the present informed consent process.

The effect of air exposure on antioxidant activities in Pacific white shrimp Litopenaeus vannamei was studied. The behavioral changes in the shrimp and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant competence (T-AOC) in the muscles and hepatopancreas were determined after the shrimp were exposed to air and then resubmersed in water. Results showed that the duration of air exposure significantly influenced shrimp survival. The maximum air exposure period during which the shrimp could remain alive was 30 min. After 10 min of air exposure, the shrimp could survive when they were resubmersed in water. The T-AOC in the hepatopancreas and muscles was significantly decreased in shrimp that were exposed to air for 20 min. The MDA content in the hepatopancreas was significantly higher for the 20-, 30-, and 40-min air exposure groups than for the control group. During the resubmersion period, the MDA content in the shrimp hepatopancreas and muscles increased. For shr...

Introduction: Numerous methods for motor unit number estimation (MUNE) have been developed. The objective of this article is to summarize and compare the major methods and the available data regarding their reproducibility, validity, appli- cation, refinement, and utility. Methods: Using specified search criteria, a systematic review of the literature was performed. Reproducibility, normative data, application to specific diseases and conditions, technical refinements, and practicality were com- piled into a comprehensive database and analyzed. Results: The most commonly reported MUNE methods are the incremental, multiple-point stimulation, spike-triggered averaging, and statistical methods. All have established normative data sets and high reproducibility. MUNE provides quantitative assessments of motor neuron loss and has been applied successfully to the study of many clinical conditions, including amyotrophic lateral sclerosis and normal aging. Conclusions: MUNE is an important research technique in human subjects, providing important data regarding motor unit populations and motor unit loss over time. Muscle Nerve 50: 884-893, 2014

Heparin-induced thrombocytopenia (HIT) is a potentially fatal clinical condition which can develop after exposure to unfractionated or low-molecular-weight heparins. Even small doses of heparin such as heparin flushes in hemodialysis catheter can induce the development of HIT. However, the true incidence of heparin lock-related HIT is unknown. We report a 58-year-old woman with acute kidney injury because of obstructive uropathy who developed HIT after heparin-free hemodialysis. She was found to have severe thrombocytopenia with deep vein thrombosis of left lower limb and arterial thrombosis of the right anterior and middle cerebral arteries. The heparin-platelet factor 4 antibody was positive and she was put on plasmapharesis. However, her condition further deteriorated and succumbed shortly. Heparin lock solution in the hemodialysis catheter was believed to be the cause of HIT in our patient.

The objective of this article is to provide a systematic review of the efficacy of electrical stimulation in healing pressure ulcer and to review its mechanism of action. The Cochrane Library, PubMed, CINAHL, Medline, EMBASE, and NHS EED were searched for relevant interventional studies including randomized controlled trials (RCTs) and observational studies. A best-evidence synthesis was performed to summarize the results of the included studies. A total of seven RCTs and two observational studies met the inclusion criteria. Moderate level of evidence of efficacy with low risk of bias was shown in all seven RCTs. Although some studies have used continuous direct current, most other investigators opted to use high-voltage pulsed current to minimize the risk of skin burn and to achieve greater current penetration. Overall, the incidence of adverse effects was very low. Two studies that assessed the economic impacts of electrical stimulation revealed substantial health care cost savings. The mechanisms through which electrical stimulation exerts a positive effect on pressure ulcer healing are reasonably well established. Clinical trials have revealed a moderate level of evidence to support its use as an ancillary treatment modality for healing pressure ulcer. Recommendations regarding the optimal electrical stimulation parameters and dosage of use are provided. Further studies to investigate potential barriers that may impede widespread use in different clinical settings are needed.

Increasingly tighter regulations regarding organic waste, and the demand for renewable chemicals and fuels, are pushing the manufacturing industry toward higher sustainability to improve cost-effectiveness and meet customers’ demand. Food waste valorization is one of the current research areas that has attracted a great deal of attention over the past few years as a potential alternative to the disposal of a wide range of residues in landfill sites. In particular, the development of environmentally sound and innovative strategies to process such waste is an area of increasing importance in our current society. Landfill, incineration and composting are common, mature technologies for waste disposal. However, they are not satisfactory to treating organic waste due to the generation of toxic methane gas and bad odor, high energy consumption and slow reaction kinetics. In fact, research efforts have also been oriented on novel technologies to decompose organic waste. However, no valuable product is generated from the decomposition process. Instead of disposing and decomposing food waste, recent research has focused on its utilization as energy source (e.g., for bioethanol and biodiesel production). Organic waste is also useful to generate useful organic chemicals via biorefinery or white biotechnology (e.g., succinic acid and/or bio-plastics). This article is aimed to summarize recent development of waste valorization strategies for the sustainable production of chemicals, materials, and fuels through the development of green production strategies. It will also provide key insights into recent legislation on management of waste worldwide as well as two relevant case studies (the transformation of corncob residues into functionalized biomass-derived carbonaceous solid acids and their utilization in the production of biodiesel-like biofuels from waste oils in Philippines, as well as the development of a bakery waste based biorefinery for succinic acid and bioplastic production in Hong Kong) to illustrate the enormous potential of biowaste valorization for a more sustainable society. Future research directions and possible sustainable approaches will also be discussed with their respective proofs of concept.

Stable and unstable spin-coated polymer films were prepared using various solvents and substrates. The relationship between polymer end-group concentrations and stability of spin-coated polymer films was revealed by time-of-flight secondary ion mass spectrometry depth profiling. A high concentration of bromine end groups at the interface between the polymer and the substrate helped to prevent the dewetting of films. In contrast, the bromine end groups were found to be more evenly distributed in unstable thin films. The extent to which the bromine end groups segregate to the interface depended on the competitive interactions between the polymer, the solvent and the substrate. Stronger polymer–solvent and solvent–substrate interactions prevented the segregation of the bromine end groups to the interface, resulting in unstable polymer films. Copyright © 2013 John Wiley & Sons, Ltd.