Relationships over time of subjective and objective elements of recovery in persons with schizophreni.
Recovery from schizophrenia involves both subjective elements such as self-appraised wellness and objective elements such as symptom remission. Less is known about how they interact. To explore this issue, this study examined the relationship over the course of 1 year of four assessments of symptoms with four assessments of self-reports of subjective aspects of recovery. Participants were 101 outpatients with schizophrenia. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) while subjective recovery was assessed with the Recovery Assessment Scale (RAS). Separate Pearson's or Spearman's rank's correlation coefficients, calculated at all four measurement points, revealed the total symptom score was linked with lower levels of overall self-recovery at all four measurement points. The PANSS emotional discomfort subscale was linked with self-reported recovery at all four measurement points. RAS subscales linked to PANSS total symptoms at every time point were Personal confidence and hope, Goal and success orientation, and No domination by symptoms. Results are consistent with conceptualizations of recovery as a complex process and suggest that while there may be identifiably different domains, changes in subjective and objective domains may influence one another.


Metformin and glucose starvation decrease the migratory ability of hepatocellular carcinoma cells: targeting AMPK activation to control migration.
Hepatocellular carcinoma (HCC) is a highly metastatic cancer with very poor prognosis. AMP activated kinase (AMPK) constitutes a candidate to inhibit HCC progression. First, AMPK is downregulated in HCC. Second, glucose starvation induces apoptosis in HCC cells via AMPK. Correspondingly, metformin activates AMPK and inhibits HCC cell proliferation. Nevertheless, the effect of AMPK activation on HCC cell invasiveness remains elusive. Here, migration/invasion was studied in HCC cells exposed to metformin and glucose starvation. Cell viability, proliferation and differentiation, as well as AMPK and PKA activation were analyzed. In addition, invasiveness in mutants of the AMPKα activation loop was assessed. Metformin decreased cell migration, invasion and epithelial-mesenchymal transition, and interference with AMPKα expression avoided metformin actions. Those antitumor effects were potentiated by glucose deprivation. Metformin activated AMPK at the same time that inhibited PKA, and both effects were enhanced by glucose starvation. Given that AMPKα(S173) phosphorylation by PKA decreases AMPK activation, we hypothesized that the reduction of PKA inhibitory effect by metformin could explain the increased antitumor effects observed. Supporting this, in AMPK activating conditions, cell migration/invasion was further impaired in AMPKα(S173C) mutant cells. Metformin emerges as a strong inhibitor of migration/invasion in HCC cells, and glucose restriction potentiates this effect.


A pilot study evaluating cutting and high-pressure balloon valvuloplasty for dysplastic pulmonary valve stenosis in 7 dogs.
This case series describes early experience and technical aspects of cutting balloon dilation followed by high-pressure balloon pulmonary valvuloplasty in dogs with dysplastic pulmonary valve stenosis. Seven client-owned dogs were enrolled in this study. Dogs were prospectively enrolled based on echocardiographic diagnosis of severe pulmonary valve dysplasia, defined as marked valve thickening with variable degrees of annular hypoplasia or subvalvar fibrous obstruction and a peak echocardiography-derived transpulmonary pressure gradient higher than 100 mmHg. Preinterventional and postinterventional hemodynamic data and transthoracic pressure gradients were obtained for all dogs. Recheck echocardiography varied in timing by client convenience, with maximum follow-up 35 months after intervention. No intraprocedural or periprocedural mortality was observed. The only major complication was partial avulsion of a cutting blade related to exceeding recommended burst pressure of the device, which was not associated with obvious clinical consequence. Invasive hemodynamic measurements demonstrated an average reduction of 46% in peak systolic right ventricular-to-pulmonary artery pressure gradient (range, 31-77%). The echocardiographic results 24 h after procedure demonstrated an average reduction in pressure gradient of 43% (range, 20-66%), with late follow-up demonstrating an average reduction of 35% (range, 10-57%) compared with preprocedural echocardiography. This procedure is a feasible therapeutic transcatheter intervention for dogs with dysplastic pulmonary valves and appears safe in this small cohort. The ideal selection criteria and rate of restenosis for this procedure is under investigation, and long-term follow-up and a large, randomized, controlled study are necessary to demonstrate efficacy.


NDH-1L with a truncated NdhM subunit is unstable under stress conditions in cyanobacteria.
Cyanobacterial NdhM, an oxygenic photosynthesis-specific NDH-1 subunit, has been found to be essential for the formation of a large complex of NDH-1 (NDH-1L). The cryo-electron microscopic (cryo-EM) structure of NdhM from Thermosynechococcus elongatus showed that the N-terminus of NdhM contains three β-sheets, while two α-helixes are present in the middle and C-terminal part of NdhM. Here, we obtained a mutant of the unicellular cyanobacterium Synechocystis 6803 expressing a C-terminal truncated NdhM subunit designated NdhMΔC. Accumulation and activity of NDH-1 were not affected in NdhMΔC under normal growth conditions. However, the NDH-1 complex with truncated NdhM is unstable under stress. Immunoblot analyses showed that the assembly process of the cyanobacterial NDH-1L hydrophilic arm was not affected in the NdhMΔC mutant even under high temperature. Thus, our results indicate that NdhM can bind to the NDH-1 complex without its C-terminal α-helix, but the interaction is weakened. NDH-1L with truncated NdhM is more prone to dissociation, and this is particularly evident under stress conditions.


Synergistic effect of UV/chlorine in bacterial inactivation, resistance gene removal, and gene conjugative transfer blocking.
Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) were investigated from effluent of two hospital and two municipal wastewater treatment plants (WWTPs) before and after disinfection. The results of network analysis showed that 8 genera were identified to be the main potential hosts of ARGs, including Mycobacterium, Ferruginibacter, Thermomonas, Morganella, Enterococcus, Bacteroides, Myroides and Romboutsia. The removal of ARGs and their possible bacterialhosts were synchronous and consistent by chlorine or ultraviolet (UV) disinfection in WWTPs. The mechanisms of ARB and ARGs removal, and conjugation transfer of RP4 plasmids by UV, chlorine and synergistic UV/chlorine disinfection was revealed. Compared to UV alone, ARB inactivation was improved 1.4 log and photoreactivation was overcomeeffectively by UV/chlorine combination (8 mJ/cm2, chlorine 2 mg/L). However, ARGs degradation was more difficult than ARB inactivation. Until UV dosage enhanced to 320 mJ/cm2, ARGs achieved 0.58-1.60 log removal. Meanwhile, when 2 mg/L of chlorine was combined with UV combination, ARGs removal enhanced 1-1.5 log. The synergistic effect of adding low-dose chlorine (1-2 mg/L) during UV radiation effectively improved ARB and ARGs removal simultaneously. The same synergistic effect also occurred in the horizontal gene transfer (HGT). Non-lethal dose chlorine (0.5 mg/L) increased the conjugation transfer frequency,which confirmed that the mRNA expression levels of type IV secretion system (T4SS) proteins vir4D, vir5B and vir10B were significantly enhanced. The risk of RP4 plasmid conjugation transfer was significantly reduced with UV/chlorine (UV ≥ 4 mJ/cm2, chlorine ≥ 1 mg/L). These findings may serve as valuable implications for assessing and controlling the risk of ARGs transfer and propagation in the environment.


A fullerene dyad with a tri(octyloxy)benzene moiety induced efficient nanoscale active layer for the poly(3-hexylthiophene)-based bulk heterojunction solar cell applications.
A bulk tri(octyloxy)benzene moiety grafted onto fullerene (PCBB-C8) was successfully synthesized, which could effectively induce poly(3-hexylthiophene) (P3HT) to form highly ordered bulk heterojunction structure without any external treatment. This ordered active layer exhibits good photovoltaic performance.


Idiopathic granulomatous mastitis: clinical, histopathological, and radiological characteristics and management approaches.
Idiopathic Granulomatous Mastitis (IGM) is an infrequent, benign breast disease that primarily affects women during their childbearing years and can be mistaken for breast cancer. This study aimed to review the clinical, radiological, and histopathological findings of patients with IGM in addition to management and outcome. Retrospective cross-sectional study of biopsy-confirmed IGM at an academic medical center and a private hospital in Amman, Jordan. Fifty-four patients were included, with a mean age of 37.0 ± 9.04 years, mostly presenting with a breast lump (n = 52, 96.3%) and breast pain (n = 45 patients, 84.9%). Approximately half of the patients (51.9%) were parous, and 50% had breastfed for an average duration of 30.37 ± 22.38 months. Most of the patients had either solitary or multiple abscesses on breast ultrasound. Histopathological analysis (n = 35) showed mostly either moderate inflammation (n = 16, 45.7%) or severe inflammation (n = 14, 40%). Two-thirds of the patients underwent surgical interventions at the time of diagnosis, mostly incision and drainage (n = 16, 29%) or surgical excision (n = 7, 13%), and no mastectomies were performed. The most common medical treatment included a combination of antibiotics, corticosteroids, and methotrexate (n = 21, 38.8%). After follow-up, 31 patients remained in remission, 3 experienced relapses, and 3 had a chronic course. The use of corticosteroids was significantly associated with remission (p = 0.035). The presentation and demographics of IGM patients in Jordan were consistent with the existing literature. Prospective research is needed to explore different treatment options and disease outcomes.


Discrepancy between subjective and objective sleepiness in adolescents.
Lack of correlation between subjective and objective measurements of daytime sleepiness is common. Here, the frequency of discrepancy between subjective and objective sleepiness, as well as possible predictors, were examined for an adolescent cohort. This study included pediatric patients (aged 10-18 years, n = 211) with various sleep disorder symptoms were evaluated between August 2011 and February 2021. Subjective and objective sleepiness were assessed based on eleven or more scores of the Japanese version of Epworth Sleepiness Scale and a mean sleep latency of 8.0 min or less on the Multiple Sleep Latency Test, respectively. Patients were then classified as both subjectively and objectively sleepy, objectively sleepy, subjectively sleepy, and non-sleepy. Discrepancy-related factors were identified with multivariable logistic regression analysis. The frequency of discrepancy between subjective and objective sleepiness was 46.4%, with 35.5% (75/211) of the patients exhibiting subjective sleepiness without objective sleepiness and 10.9% (23/211) of the patients exhibiting objective sleepiness without subjective sleepiness. Co-existence of neurodevelopmental disorders was associated more often with subjective sleepiness compared to non-sleepiness (odds ratio (OR), 4.12; 95% confidence interval (CI), 1.30 to 12.99) or concordant sleepiness (OR, 7.54; 95% CI, 2.43 to 23.38). Nearly half of the patients exhibited discrepancy between subjective and objective sleepiness, and it more often involved subjective sleepiness. Furthermore, age, bedtime, and neurodevelopmental disorders were identified as significant factors related to subjective sleepiness without objective sleepiness.


Reciprocal regulation of capacitative and non-capacitative Ca2+ entry in A7r5 vascular smooth muscle cells: only the latter operates during receptor activation.
In A7r5 vascular smooth muscle cells, Arg(8)-vasopressin (AVP) stimulates phospholipase C leading to activation of two distinct Ca(2+) entry pathways. The capacitative Ca(2+) entry (CCE) pathway is activated by depletion of Ca(2+) stores, is permeable to Mn(2+), Ba(2+) and Ca(2+), and is selectively blocked by Gd(3+)(1 microM). A7r5 cells also express a non-capacitative Ca(2+) entry (NCCE) pathway, which is activated by arachidonic acid that is released by the sequential activities of phospholipase C and diacylglycerol lipase. This pathway is permeable to Sr(2+), Ba(2+) and Ca(2+) and selectively blocked by (R,S)-(3,4-dihydro-6,7-dimethoxy-isochinolin-1-yl)-2-phenyl-N,N-di[2-(2,3,4-trimethoxyphenyl)ethyl]acetamid mesylate ("LOE-908"). We use these selective tools to show that AVP, via the same signalling pathway that leads to activation of NCCE, also inhibits CCE and that the inhibition is not due to depolarization of the plasma membrane. Using the selective inhibitors to resolve the contributions of each Ca(2+) entry pathway during stimulation with AVP, we establish that reciprocal regulation of CCE and NCCE by arachidonic acid ensures that only NCCE is active in the presence of AVP, whereas CCE is active only after its removal. NCCE and CCE are therefore activated in a strict temporal sequence: NCCE first and then CCE. Because Ca(2+) passing through different Ca(2+) entry pathways can selectively regulate different responses, reciprocal regulation of CCE and NCCE may allow a stimulus to first evoke a response and then recruit actively a different response when the stimulus is removed.


AGPAT2 gene mutation in a child with Berardinelli-Seip congenital lipodystrophy syndrome.
Berardinelli-Seip congenital lipodystrophy (BSCL) syndrome is an autosomal recessive disorder, caused by mutation in the AGPAT2 gene, which could lead to insulin resistance and variety of complications. Herein, a 7-year old girl is presented with generalized loss of subcutaneous fat, prominent pectoral and thigh muscles and an early telarche. Laboratory studies revealed an elevated level of serum triglyceride. Ultrasonograph demonstrated enhanced size of ovary containing multiple mature follicles. Considering the clinical phenotype, AGPAT2 gene was sequenced which showed homozygote c.514G>A mutation. Therefore, the diagnosis of BSCL was confirmed in this patient.


Development of single-chain variable fragments (scFv) against influenza virus targeting hemagglutinin subunit 2 (HA2).
Influenza A viruses (IAV) are widespread in birds and domestic poultry, occasionally causing severe epidemics in humans and posing health threats. Hence, the need to develop a strategy for prophylaxis or therapy, such as a broadly neutralizing antibody against IAV, is urgent. In this study, single-chain variable fragment (scFv) phage display technology was used to select scFv fragments recognizing influenza envelope proteins. The Tomlinson I and J scFv phage display libraries were screened against the recombinant HA2 protein (rHA2) for three rounds. Only the third-round elution sample of the Tomlinson J library showed high binding affinity to rHA2, from which three clones (3JA18, 3JA62, and 3JA78) were chosen for preparative-scale production as soluble antibody by E. coli. The clone 3JA18 was selected for further tests due to its broad affinity for influenza H1N1, H3N2 and H5N1. Simulations of the scFv 3JA18-HA trimer complex revealed that the complementarity-determining region of the variable heavy chain (VH-CDR2) bound the stem region of HA. Neutralization assays using a peptide derived from VH-CDR2 also supported the simulation model. Both the selected antibody and its derived peptide were shown to suppress infection with H5N1 and H1N1 viruses, but not H3N2 viruses. The results also suggested that the scFvs selected from rHA2 could have neutralizing activity by interfering with the function of the HA stem region during virus entry into target cells.


Transcriptional and metabolomic investigation of the stress response in snow crab during simulated transport condition (Chionoecetes opilio).
The molecular mechanisms underlying the stress response are poorly described in crustaceans. This includes the snow crab (Chionoecetes opilio), a commercially important stenotherm species distributed throughout the northern hemisphere. A better understanding of the stress response in C. opilio is desperately needed for commercial and conservation purposes. The purpose of this study was to investigate the transcriptional and metabolomic response of C. opilio exposed to stressors. Crabs were randomly assigned to 24 or 72 h treatment groups where they were exposed to conditions simulating live transport (handling and air exposure). A control group was kept in cold (2 °C) and well‑oxygenated saltwater. The hepatopancreas of the crabs was sampled to perform RNA-sequencing and high-performance chemical isotope labeling metabolomics. Differential gene expression analyses showed that classic crustaceans' stress markers, such as crustacean hyperglycemic hormones and heat shock proteins, were overexpressed in response to stressors. Tyrosine decarboxylase was also up-regulated in stressed crabs, suggesting an implication of the catecholamines tyramine and octopamine in the stress response. Deregulated metabolites revealed that low oxygen was an important trigger in the stress response as intermediate metabolites of the tricarboxylic acid cycle (TCA) accumulated. Lactate, which accumulated unevenly between crabs could potentially be used to predict mortality. This study provides new information on how stressors affect crustaceans and provides a basis for the development of stress markers in C. opilio.


Reliability of Pulse Contour Cardiac Output Analysis in a Piglet Model of Multi-step Intra-abdominal Hypertension.
Pulse contour cardiac output (PCCO) analysis is a minimally invasive technique for continuous cardiac output (CO) measurement monitoring. PCCO requires calibration by transpulmonary thermodilution (TPTD). Studies showed good agreement between PCCO, TPTD CO and CO measured by pulmonary artery thermodilution (PATD) during stable hemodynamics. However, data are limited in patients with intra-abdominal hypertension (IAH). The objective is to compare the agreement between PCCO, TPTD CO, and PATD CO in a piglet model of multi-step IAH. Ten female domestic piglets were enrolled in this study. IAH was induced by stepwise carbon dioxide inflation into peritoneal cavity in anesthetized piglets. Following baseline registrations, intra-abdominal pressure (IAP) was increased and maintained at each IAP plateau of 10, 20, 30, and 40 mmHg for 15 min before CO measurements. CO was measured by PATD and simultaneously by 2 femoral artery PCCO catheters. One PCCO catheter was recalibrated by TPTD at each IAP plateau while the other was only calibrated at baseline. In pooled data of different IAP stages, TPTD CO and recalibrated PCCO (R-PCCO) showed excellent correlation (r2 = 0.94 and 0.93) and small bias (-0.09 and -0.09 L/min), respectively, compared with PATD CO. However, PCCO without recalibration (NR-PCCO) were not accurate during IAH (r2 = 0.58, bias: +0.32 L/min). When IAP increased to 30 mmHg, NR-PCCO failed to agree with PATD CO (r2 = 0.47, bias: +0.52 L/min). On the contrary, a clinically accepted agreement between TPTD CO, R-PCCO, and PATD CO was observed at different IAP stages. TPTD CO and R-PCCO agreed with PATD CO in this piglet model of multi-step IAH. On the contrary, NR-PCCO failed to agree with PATD CO when IAP increased to 30 mmHg or more. PCCO analysis needs recalibration in this condition.


Clinical evaluation for osteoporosis.
The clinical evaluation of the osteoporotic patient should include a careful assessment of risk factors for low bone mass, falls, and fractures; quantitation of BMD; a thorough medical history and physical examination; and a targeted set of laboratory, radiographic, and other diagnostic studies as indicated. Among the elderly, vitamin D deficiency ranks high as one of the most underdiagnosed and yet reversible causes of osteoporosis. Regardless of age, every patient with low bone mass or fractures deserves an evaluation to uncover reversible, treatable disorders and to detect serious underlying illnesses.


Associations between dietary patterns and gene expression pattern in peripheral blood mononuclear cells: A cross-sectional study.
Diet may alter gene expression in immune cells involved in atherosclerotic cardiovascular disease susceptibility. However, we still lack a robust understanding of the association between diet and immune cell-related gene expression in humans. Therefore, we examined associations between dietary patterns (DPs) and gene expression profiles in peripheral blood mononuclear cells (PBMCs) in a population of healthy, Norwegian adults (n = 130 women and 105 men). We used factor analysis to define a posteriori DPs from food frequency questionnaire-based dietary assessment data. In addition, we derived interpretable features from microarray-based gene expression data (13 967 transcripts) using two algorithms: CIBERSORT for estimation of cell subtype proportions, and weighted gene co-expression network analysis (WGCNA) for cluster discovery. Finally, we associated DPs with either CIBERSORT-predicted PBMC leukocyte distribution or WGCNA gene clusters using linear regression models. We detected three DPs that broadly reflected Western, Vegetarian, and Low carbohydrate diets. CIBERSORT-predicted percentage of monocytes associated negatively with the Vegetarian DP. For women, the Vegetarian DP associated with a large gene cluster consisting of 600 genes mainly involved in regulation of DNA transcription, whereas for men, the Western DP inversely associated with a smaller cluster of 36 genes mainly involved in regulation of metabolic and inflammatory processes. A subsequent protein-protein interaction network analysis suggested that genes within these clusters might physically interact in biological networks. Although the present findings are exploratory, our analysis pipeline serves as a useful framework for studying the association between diet and gene expression.


Transcriptome analysis reveals new insights into immune response to hypoxia challenge of large yellow croaker (Larimichthys crocea).
Fish live in direct contact with aquatic environment, which exhibits much wider temporal and spatial variations in oxygen content. The molecular mechanisms underlying fish response to hypoxia have become a subject of great concern in recent years. In the present study, we performed transcriptome analysis of spleen and head kidney tissues from large yellow croaker (Larimichthys crocea) at 6 h, 24 h and 48 h after hypoxia challenge. A total of 2,499 and 3,685 differentially expressed genes (DEGs) were obtained in spleen and head kidney, respectively. The expression changes of 10 selected genes in each tissue were further validated by quantitative real-time PCR. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichments revealed that numerous DEGs were immune genes, involved in multiple immune-relevant pathways. In spleen, several pattern recognition receptors (PRRs), including Toll-like receptors (TLR1, TLR2-1, TLR2-2, TLR5 and TLR8), Fucolectins (FUCL1, FUCL4 and FUCL5) and macrophage mannose receptor (MRC1), were significantly down-regulated, suggesting that the immune processes mediated by these PRRs may be suppressed by hypoxia stress. However, some PRRs (FUCL4, FUCL5 and MRC1) and other innate immunity genes, such as C-type lectin domain gene family members, chemokines, chemokine receptors and complement components were up-regulated in head kidney, which may be due to the increases in phagocytosis and cytokine secretion by macrophages after hypoxic stimulus. The expression of genes involved in B cell receptor signaling pathway, Natural killer cell-mediated cytotoxicity and NF-κB signaling pathway decreased rapidly, but regained normal or increased over time, suggesting an early adjustment pattern of fish immune response to cope with hypoxia stress. Moreover, the anaerobic ATP-generating pathway was activated and energy consumption processes were repressed concurrently in both spleen and head kidney. These data provide valuable information for understanding the tissue-specific and temporal changes of immune gene expression in hypoxic large yellow croakers.


Establishment of a CD4-positive cell line from an AIDS-related primary effusion lymphoma.
Primary effusion lymphoma (PEL) presents as a serous lymphomatous effusion without tumor masses exclusively in body cavities and mainly occurs in human immunodeficiency virus-1 (HIV-1)-infected patients. We established a new PEL cell line, designated GTO, from the pericardial effusion of a 39-year-old Japanese patient with acquired immunodeficiency syndrome-related PEL. This cell line was infected with human herpesvirus-8, but not with Epstein-Barr virus. Southern blot hybridization demonstrated that GTO cells display monoclonal rearrangement of the IgH gene, suggesting clonal B cell proliferation. GTO cells weakly express or lack T cell-associated markers (CD3, CD5, CD8), the majority of B cell-associated markers (CD19, CD20, CD21, CD79a), the α chains of β 2 integrins (CD11a, CD11b, CD11c), HLA-DR, CD30, and surface immunoglobulin (sIgM, sIgG sIgκ, sIgλ), TCR (α/β, γδ), but express CD45, and post-germinal center B cell/plasma cell-associated antigens (CD38, CD138). They also express a high level of cell-surface CD4 and can be infected by HIV-1. Immunodeficient mice intraperitoneally xenografted with GTO cells developed ascites containing lymphoma cells. The establishment of GTO and a GTO xenograft mouse model may help to provide insights toward a better understanding of the pathogenesis of PEL and the relationship between HIV-1 and HHV-8.


Comparison of sex chromosome aneuploidy in spermatozoa of fertile men and those requiring ICSI treatment detected by fluorescence in situ hybridization.
To compare the frequencies of aneuploidy for chromosomes X, Y and 18 in spermatozoa of infertile and fertile males, using 3-color fluorescence in situ hybridization. Twelve infertile patients who underwent intracytoplasmic sperm injection treatment at Queen's Medical Centre, Nottingham were studied. Three fertile men served as controls. Aneuploidy frequencies in both groups were compared using 2-sample t-tests. A total of 26,615 ad 93,649 cells were scored in the control and infertile groups respectively. The frequencies of diploidy, sex chromosome disomy and chromosome 18 disomy in the fertile (0.11, 0.28 and 0.11%) compared to the infertile males (0.05, 0.18 and 0.06%) were not statistically significantly different. Our preliminary data do not indicate an increased risk from paternal origin sex chromosome aneuploidies in ICSI. However, we recommend further investigations of the cytogenetic constitution of spermatozoa from severe male factor patients.


Direct interaction of tumor suppressor CEACAM1 with beta catenin: identification of key residues in the long cytoplasmic domain.
CEACAM1-4L (carcinoembryonic antigen cell adhesion molecule 1, with 4 extracellular Ig-like domains and a long, 71 amino acid cytoplasmic domain) is expressed in epithelial cells and activated T-cells, but is down-regulated in most epithelial cell cancers and T-cell leukemias. A highly conserved sequence within the cytoplasmic domain has ca 50% sequence homology with Tcf-3 and -4, transcription factors that bind beta-catenin, and to a lesser extent (32% homology), with E-cadherin that also binds beta-catenin. We show by quantitative yeast two-hybrid, BIAcore, GST-pull down, and confocal analyses that this domain directly interacts with beta-catenin, and that H-469 and K-470 are key residues that interact with the armadillo repeats of beta-catenin. Jurkat cells transfected with CEACAM1-4L have 2-fold less activity in the TOPFLASH reporter assay, and in MCF7 breast cancer cells that fail to express CEACAM1, transfection with CEACAM1 and growth in Ca2+ media causes redistribution of beta-catenin from the cytoplasm to the cell membrane, demonstrating a functional role for the long cytoplasmic domain of CEACAM1 in regulation of beta-catenin activity.


New 29-mm balloon-expandable prosthesis for transcatheter aortic valve implantation in large annuli.
An important number of patients are considered unsuitable for transcatheter aortic valve implantation because of a large native aortic valve. A new 29-mm balloon-expandable transcatheter valve offers the option to gain a maximal effective orifice area without paravalvular leakage. This study sought to define ranges of safe applicability in terms of device landing zone geometry. A second purpose was to determine performance of the prosthesis and clinical outcome. Between April 2011 and July 2012, the new 29-mm SAPIEN XT prosthesis was implanted by means of transapical access in 78 patients with large aortic annuli. The study group represents 32.9% of all transapical transcatheter aortic valve implantations performed at our institution during the observation period; 82 patients receiving 26-mm prosthesis served as a control group. Device landing zone morphology was analyzed by echocardiography and computed tomography. The postimplant effective orifice area (study versus control group) was 2.7 cm(2) (interquartile range, 2.3 to 3.0 cm(2)) and 2.1 cm(2) (interquartile range, 1.7 to 2.4 cm(2)), respectively (p < 0.001), without any severe patient-prosthesis mismatch. Postprocedural regurgitation was similar in both groups (p = 0.892): absent in 56 (71.8%) and 54 (65.9%) patients, trace or mild in 21 (26.9%) and 27 (32.9%), and moderate in 1 (1.3%) and 1 (1.2%), respectively. Including patients in cardiogenic shock, the overall 30-day mortality rate of the study and control groups was 5.1% and 1.2%, respectively. One-year survival was 76.7% ± 8.6% with no difference from control patients (p = 0.743). The new 29-mm balloon-expandable prosthesis broadens the indication for transcatheter aortic valve implantation to include patients with large annuli. The outcome is very favorable.


Fluorescence polarization immunoassay for the determination of diclofenac in wastewater.
Pharmacologically active compounds are often detected in wastewater and surface waters. The nonsteroidal anti-inflammatory drug diclofenac (DCF) was included in the European watch list of substances that requires its environmental monitoring in the member states. DCF may harmfully influence the ecosystem already at concentrations ≤ 1 μg L-1. The fast and easy quantification of DCF is becoming a subject of global importance. Fluorescence polarization immunoassay (FPIA) is a homogeneous mix-and-read method which does not require the immobilization of reagents. FPIA can be performed in one phase within 20-30 min, making it possible to analyse wastewater without any complicated pre-treatment. In this study, new tracer molecules with different structures, linking fluorophores to derivatives of the analyte, were synthesized, three homologous tracers based on DCF, two including a C6 spacer, and one heterologous tracer derived from 5-hydroxy-DCF. The tracer molecules were thoroughly assessed for performance. Regarding sensitivity of the FPIA, the lowest limit of detection reached was 2.0 μg L-1 with a working range up to 870 μg L-1. The method was validated for real wastewater samples against LC-MS/MS as reference method with good agreement of both methods. Graphical abstract.


Recovery of atrial contractile function after cut-and-sew maze for long-standing persistent valvular atrial fibrillation.
The recovery of atrial contractile (AC) after maze has been concerned and even questioned. Now, studied the AC recovery degree and its influencing factors. 237 patients with valvular long-standing persistent atrial fibrillation (AF) were retrospectively grouped according to whether sinus rhythm(SR) maintained and AC restored: SR-AC (163 cases), SR-no-AC (41 cases) and AF-no-AC (33 cases). SR-AC were grouped according to Em/Am ratio. Em/Am≤2 showed that the AC recovered well. The SR maintained rate (161/177, 90.96%) in patients underwent the cut-and-sew maze III (CSM) was significantly higher than that in cryoablation (43/60, 71.7%). Preoperative AF duration had no significant difference among three groups (P = 0.679). Maze methods had significant relationship with whether SR recovered, P < 0.05, but no significant relationship with whether AC recovered in SR maintained patients (P = 0.280). Nearly 80% (163/204) patients can recover AC, among 156 patients (156/204, 76.5%) recovered contractile of left and right atrium, and 63 (63/204, 30.1%) recovered significant left atrial contractile, that is, Em/Am≤2. Whether AC was significantly restored was not related to maze methods, P = 0.370. AC recovered degree in rheumatic heart disease (RHD) patients was worse than that in mitral valve prolapse (MVP) patients, P = 0.004. To sum up, the CSM is safe and effective, and the atrial contractile function recovery was found in 80%. The key to the success of maze is to form a complete and lasting electrical isolation, and there was no difference in the rate of atrial contractile recovery when postoperative SR was maintained, no matter what maze method is used. MVP patients should be treated with maze more actively than RHD patients.


A new technique for and additional experience with hysteroscopic resection of submucous fibroids.
New instrumentation and a new technique are described which simplify the hysteroscopic removal of the pedunculated submucous fibroid and make possible the partial removal of the sessile variety. Experience with the method is presented including the follow-up of four patients.


Depletion of 5-HT disrupts prepulse inhibition in rats: dependence on the magnitude of depletion, and reversal by a 5-HT precursor.
The 5-HT(1A) agonist 8-OH-DPAT has been reported to disrupt prepulse inhibition (PPI) of the acoustic startle reflex after local administration into the raphe nuclei. Because it is likely that 8-OH-DPAT disrupted PPI by activation of somatodendritic inhibitory receptors, and thereby, via a decrease in 5-HT neurotransmission, we tested whether chronic, drug-induced, depletions of 5-HT have similar effects. Rats were drug-treated for three consecutive days and tested in a short PPI paradigm on day 4, and retested 2 h later, after acute saline or drug administration. Repeated treatment with the 5-HT synthesis inhibitor p-chlorophenylalanine methyl ester (PCPA; 160 mg/kg) produced a small, but significant, attenuation of PPI, and a large decrease in extracellular 5-HT levels in the hippocampus, as measured in independent microdialysis experiments. An even larger depletion of 5-HT was obtained by substituting the 3(rd) PCPA administration with the 5-HT releaser d-fenfluramine (10 mg/kg); this combined treatment nearly abolished PPI in the majority of animals. The involvement of 5-HT in the latter effects was confirmed by the finding that low doses of the 5-HT precursor 5-hydroxy-L-tryptophan reinstated PPI during retest. These data, together with recently published studies, provide strong evidence that pharmacologically-induced depletion of 5-HT disrupts PPI.


(E)-2-[(E)-3-(Hy-droxy-imino)-butan-2-yl-idene]-N-methyl-hydrazinecarbothio-amide.
In the title compound, C(6)H(12)N(4)OS, an intra-molecular N-H⋯N hydrogen-bond is present giving rise to an S(5) ring motif. In the crystal, double-stranded chains propagating along [10[Formula: see text]] are formed via pairs of O-H⋯S and N-H⋯S hydrogen bonds. The chains are further stabilized by C-H⋯S interactions.


Effect of oral exposure on chemical, physical, mechanical, and morphologic properties of clear orthodontic aligners.
The dental industry is heavily committed to developing more esthetic solutions for orthodontic treatments. Invisalign is a system of transparent orthodontic aligners introduced as an alternative to conventional orthodontic fittings with brackets and metal wires. This study aimed to assess the chemical, physical, mechanical and morphologic changes in these polymeric aligners after exposure to the oral environment. Twenty-four Invisalign orthodontic aligners were equally divided into 2 groups: an in vivo aged group in which patients used aligners for 14 days and the reference group, unexposed to the oral environment. Different experimental techniques were used to study the chemical structure, the color changes and translucency, the density and subsequent volume of the aligners, mechanical properties, surface roughness, morphology and elemental composition. The data were subjected to several statistical analyses. Clear orthodontic aligners exhibit chemical stability but undergo a statistically significant optical change in color and translucency. There was a gradual increase in the water absorption rate and the dimensional variation of the polymer, indicating a strong correlation among these factors. The mechanical properties of the polymer showed a statistically significant decrease in its elastic modulus and hardness. There was a slight tendency toward increased surface roughness of the material, but no statistical differences were found between reference and aged groups. The surface morphology of the used aligners demonstrates microcracks, distortions and biofilm formation. Intraoral aging adversely affected the physical, mechanical, and morphologic properties of the Invisalign appliance.


Outcomes of 8 × 8 mm osteotomy in powered external dacryocystorhinostomy.
To study the endoscopic ostium characteristics and outcome of 8 × 8 mm osteotomy in external dacryocystorhinostomy (DCR) using the microdrill system. This prospective interventional pilot study was performed on 40 eyes of 40 patients with primary acquired nasolacrimal duct obstruction (NLDO) from June 2021 to September 2021 in patients undergoing external DCR. An 8 × 8 mm osteotomy was performed using round, cutting burr attached to a microdrill system. Success was defined as patent ostium on lacrimal syringing (anatomical) and a Munk score <3 (functional) at 12 months. Postoperative endoscopic ostium evaluation was done using a modified DCR ostium (DOS) scoring system at 12 months. The mean age of the study participants was 42.41 ± 11.77 years and the male-to-female ratio was 1:4. The mean duration of surgery was 34.15 ± 1.66 minutes and that for osteotomy creation was 2.5 ± 0.69 minutes. The mean intraoperative blood loss was 83.37 ± 11.89 ml. Anatomical and functional success rates were 95% and 85%, respectively. The mean modified DOS score was "excellent" in 34 patients (85%), "good" in 1 patient (2.5%), "fair" in 4 patients (10%), and "poor" in 1 patient (2.5%). Complications included nasal mucosal injury in 10% (4/40) of patients, complete cicatricial closure of ostium in 2.5% (1/40), incomplete cicatricial closure in 10% (4/40), nasal synechiae in 5% (2/40), and canalicular stenosis in 2.5% (1/40). An 8 × 8 mm-sized osteotomy created by powered drill and covered by lacrimal sac-nasal mucosal flap anastomosis in external DCR is an effective technique that has minimal complications and shorter surgical time.


Safety of delayed surgical repair of omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex in infants with significant comorbidities.
Management of infants with OEIS complex is challenging and not standardized. Expeditious surgery after birth has been recommended to limit soilage of the urinary tract and optimize intestinal function. However, clinical instability secondary to comorbidities is common in this population and early operation carries risk. We sought to define the risk/benefit profile of delaying repair. All newborn patients with OEIS managed by our institution between Sep 2017 and Oct 2019 were reviewed. Comorbidities were evaluated, including cardiopulmonary pathologies and associated malformations. Ten patients with OEIS were managed. Patients underwent early (2 patients, repair at 0-2 days) or delayed (6 patients, repair at 6-87 days) first-stage exstrophy repair. Two patients died prior to repair (progressive respiratory failure, severe genetic anomalies). Repairs were delayed secondary to cardiac conditions, neurosurgical interventions, medical disease, and/or delayed transfer. Delayed repair patients had longer lengths of stay and use of parenteral nutrition. No patients experienced urinary tract infections prior to repair. Delaying first-stage exstrophy repair to allow physiologic optimization is safe. All repaired patients were discharged home, without parenteral nutrition or supplemental oxygen.


Techniques of Human Embryonic Stem Cell and Induced Pluripotent Stem Cell Derivation.
Developing procedures for the derivation of human pluripotent stem cells (PSCs) gave rise to novel pathways into regenerative medicine research. For many years, stem cells have attracted attention as a potentially unlimited cell source for cellular therapy in neurodegenerative disorders, cardiovascular diseases, and spinal cord injuries, for example. In these studies, adult stem cells were insufficient; therefore, many attempts were made to obtain PSCs by other means. This review discusses key issues concerning the techniques of pluripotent cell acquisition. Technical and ethical issues hindered the medical use of somatic cell nuclear transfer and embryonic stem cells. Therefore, induced PSCs (iPSCs) emerged as a powerful technique with great potential for clinical applications, patient-specific disease modelling and pharmaceutical studies. The replacement of viral vectors or the administration of analogous proteins or chemical compounds during cell reprogramming are modifications designed to reduce tumorigenesis risk and to augment the procedure efficiency. Intensified analysis of new PSC lines revealed other barriers to overcome, such as epigenetic memory, disparity between human and mouse pluripotency, and variable response to differentiation of some iPSC lines. Thus, multidimensional verification must be conducted to fulfil strict clinical-grade requirements. Nevertheless, the first clinical trials in patients with spinal cord injury and macular dystrophy were recently carried out with differentiated iPSCs, encouraging alternative strategies for potential autologous cellular therapies.


The synergistic action of the capsule and the shoulder muscles.
The existence of a reflex arc from the glenohumeral capsule to several muscles crossing the shoulder joint was determined in the feline model. Three branches of the axillary nerve terminating in the glenohumeral capsule were identified and electrically stimulated with supramaximal, 100-microseconds pulses using bipolar hook electrodes. Stimulation of the anterior and the inferior axillary articular nerves elicited electromyographic activity in the biceps, subscapularis, supraspinatus, and infraspinatus muscles. Stimulation of the posterior axillary articular nerve elicited electromyographic activity in the acromiodeltoid muscle. Transection of the three articular nerves just distal to their emergence from the main axillary nerve resulted in the absence of any electromyographic activity in the muscles on stimulation, confirming the afferent nature of the articular branches. The time from application of the stimulus to the appearance of a response in the muscles varied from 2.7 msec in the biceps to 3.1 msec in the supraspinatus. The existence of a reflex arc from mechanoreceptors within the glenohumeral capsule to muscles crossing the joint confirms and extends the concept of synergism between the passive (ligaments) and active (muscles) restraints of the glenohumeral joint. This provides new information in orthopaedic sciences that has direct application in modification of surgical repairs and therapeutic modalities of shoulder injuries.


Functional mapping of an AcNPV immediately early gene which augments expression of the IE-1 trans-activated 39K gene.
An early gene which augments the expression of the delayed early/late 39K gene of the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV) was identified by functional mapping. Transient expression of the plasmid p39CAT, containing the bacterial chloramphenicol acetyltransferase coding sequences under the control of the promoter of the 39K protein, was observed in cells cotransfected with AcNPV DNA digested with several restriction endonucleases. However, when p39CAT was cotransfected with viral DNA digested with Bg/II restriction endonuclease, no CAT activity could be detected. To map the location of the Bg/II-sensitive sequences required for efficient expression of 39CAT, p39CAT and Bg/II-digested viral DNA were cotransfected with a PstI library of AcNPV DNA. The PstI-N fragment restored 39CAT activity. A major early 1.3-kb transcript from this fragment was mapped by S1 nuclease analysis. Transient assay experiments indicated that this major transcript of the PstI-N fragment was produced by an immediate early gene, named IE-N. The PstI-N fragment alone did not activate expression of p39CAT but was required when IE-1 was present in limiting quantities.


The analysis of progress curves for enzyme-catalysed reactions by non-linear regression.
A procedure, based on the Gauss-Newton method for non-linear regression, has been developed to obtain enzyme kinetic constants from the analysis of progress curve data. Rules are presented which greatly simplify the derivation of the necessary equations. The method has been applied to the reactions catalysed by prephenate dehydratase, acid phosphatase and lactate dehydrogenase and has yielded values for kinetic parameters which agree well with those obtained from steady-state rate measurements.


Identification of radioactive insulin fragments liberated by insulin proteinase during the degradation of semisynthetic [3H]GlyA1]insulin and [3H]PheB1]insulin.
(1) We [Muir, Offord & Davies (1986) Biochem. J. 237, 631-637 and Davies, Muir & Offord (1986) Biochem. J. 240, 609-612] have previously identified a major product in the degradation of insulin by insulin proteinase (the N-terminal fragment produced by cleavage between residues LeuA13 and TyrA14, SerB9 and HisB10) together with evidence for a minor cleavage site between HisB10 and LeuB11 or between LeuB11 and ValB12. (2) We now present evidence for minor sites of cleavage between TyrA14 and GlnA15, GluB13 and AlaB14 as well as HisB10 and LeuB11.


The adequacy of pharmaceutical treatment of schizophrenia in Quebec varies with age, but is not influenced by sex or neighbourhood deprivation.
Though high discontinuation rates for antipsychotics (APs) by patients with schizophrenia are frequently reported, the percentage of patients receiving pharmaceutical treatment for schizophrenia in routine practice in accordance with international clinical guidelines is unknown. Further, it is unknown if these rates are influenced by levels of neighbourhood deprivation or by a patient's age or sex. Our study aims to investigate if inequalities in AP treatment could be observed between patients living in neighbourhoods with the highest levels of material and social deprivation and those with the lowest deprivation levels, between patients from different age groups, or between men and women. We conducted a secondary analysis of medical-administrative data of a cohort of adult patients in the province of Quebec with a medical contact for schizophrenia in a 2-year period (2004-2005). We assessed the proportion of patients that filled at least 1 prescription for an AP and received adequate pharmaceutical treatment, defined as being in possession of APs at least 80% of the time as outpatients during a 2-year follow-up period. Among the 30 544 study patients, 88.5% filled at least 1 prescription for an AP, and 67.5% of the treated patients received adequate treatment. Though no clinically significant differences were observed by deprivation or sex, younger age was associated with lower proportions of patients receiving adequate treatment (46% of treated patients aged between 18 and 29 years, compared with 72% aged between 30 and 64 years, and 77% aged 65 years and over). In Quebec's routine practice, over 70% of treated patients aged 30 and over received adequate pharmacological treatment, regardless of sex or neighbourhood socioeconomic status. In contrast, in patients aged between 18 and 29 years this percentage was 47%. This is a discouraging finding, especially because optimal treatment in the early phase of disease is reported to result in the best long-term outcomes.


Detection and discrimination of neutron capture events for NCEPT dose quantification.
Neutron Capture Enhanced Particle Therapy (NCEPT) boosts the effectiveness of particle therapy by capturing thermal neutrons produced by beam-target nuclear interactions in and around the treatment site, using tumour-specific [Formula: see text]B or [Formula: see text]Gd-based neutron capture agents. Neutron captures release high-LET secondary particles together with gamma photons with energies of 478 keV or one of several energies up to 7.94 MeV, for [Formula: see text]B and [Formula: see text]Gd, respectively. A key requirement for NCEPT's translation is the development of in vivo dosimetry techniques which can measure both the direct ion dose and the dose due to neutron capture. In this work, we report signatures which can be used to discriminate between photons resulting from neutron capture and those originating from other processes. A Geant4 Monte Carlo simulation study into timing and energy thresholds for discrimination of prompt gamma photons resulting from thermal neutron capture during NCEPT was conducted. Three simulated [Formula: see text] mm[Formula: see text] cubic PMMA targets were irradiated by [Formula: see text]He or [Formula: see text]C ion beams with a spread out Bragg peak (SOBP) depth range of 60 mm; one target is homogeneous while the others include [Formula: see text] mm[Formula: see text] neutron capture inserts (NCIs) of pure [Formula: see text]B or [Formula: see text]Gd located at the distal edge of the SOBP. The arrival times of photons and neutrons entering a simulated [Formula: see text] mm[Formula: see text] ideal detector were recorded. A temporal mask of 50-60 ns was found to be optimal for maximising the discrimination of the photons resulting from the neutron capture by boron and gadolinium. A range of candidate detector and thermal neutron shielding materials were simulated, and detections meeting the proposed acceptance criteria (i.e. falling within the target energy window and arriving 60 ns post beam-off) were classified as true or false positives, depending on their origin. The ratio of true/false positives ([Formula: see text]) was calculated; for targets with [Formula: see text]B and [Formula: see text]Gd NCIs, the detector materials which resulted in the highest [Formula: see text] were cadmium-shielded CdTe and boron-shielded LSO, respectively. The optimal irradiation period for both carbon and helium ions was 1 µs for the [Formula: see text]B NCI and 1 ms for the [Formula: see text]Gd NCI.


Artificial phototropism for omnidirectional tracking and harvesting of light.
Many living organisms track light sources and halt their movement when alignment is achieved. This phenomenon, known as phototropism, occurs, for example, when plants self-orient to face the sun throughout the day. Although many artificial smart materials exhibit non-directional, nastic behaviour in response to an external stimulus, no synthetic material can intrinsically detect and accurately track the direction of the stimulus, that is, exhibit tropistic behaviour. Here we report an artificial phototropic system based on nanostructured stimuli-responsive polymers that can aim and align to the incident light direction in the three-dimensions over a broad temperature range. Such adaptive reconfiguration is realized through a built-in feedback loop rooted in the photothermal and mechanical properties of the material. This system is termed a sunflower-like biomimetic omnidirectional tracker (SunBOT). We show that an array of SunBOTs can, in principle, be used in solar vapour generation devices, as it achieves up to a 400% solar energy-harvesting enhancement over non-tropistic materials at oblique illumination angles. The principle behind our SunBOTs is universal and can be extended to many responsive materials and a broad range of stimuli.


Delayed union of multifragmentary diaphyseal fractures after bridge-plate fixation.
Despite recent developments in fracture treatment, cases of non-union after long bone fractures are still encountered. This work aims at evaluating the active management of delayed union after the bridge-plate fixation of multifragmentary diaphyseal fractures by a limited surgical interference. Nineteen patients were included. All had revision surgery for delayed union of multifragmentary diaphyseal fractures after bridge-plate fixation. The period between primary and revision surgery was 12-20 weeks. Increasing stability was performed by adding more screws in all cases. Interfragmentary compression was performed in 16 patients. Axial compression of the fracture was applied in two patients, while one patient had the plate exchanged for a longer one. Bone grafting was added in nine patients. Union was achieved in all patients 8-16 weeks after re-operation. This work is a message for timely surgical interference in delayed union after bridge-plate fixation by a limited surgical procedure, before complete failure of the fracture stabilisation or non-union.


Graphene sheets, polyaniline and AuNPs based DNA sensor for electrochemical determination of BCR/ABL fusion gene with functional hairpin probe.
A sensitive and selective electrochemical DNA sensor was developed for the detection of BCR/ABL fusion gene in chronic myelogenous leukemia (CML). Firstly, graphene sheets (GS) suspension was prepared with the aid of chitosan (CS) solution and then fabricated onto the glassy carbon electrode (GCE), followed by the electro-polymerization of aniline to form the PANI layer, then, Au nanoparticles (AuNPs) were electro-deposited onto the modified GCE to immobilize the capture probes. The capture probe employed a hairpin structure and dually labeled with a 5'-SH and a 3'-biotin. After hybridization with the target DNA, hairpin structure was compelled to open and 3'-biotin was forced to stay away from the electrode surface. As a result, streptavidin-alkaline phosphatase (SA-AP) was covalently binded to the capture probe via biotin-avidin system. Reduction currents were then generated after catalyzing the hydrolysis of the electroinactive 1-naphthyl phosphate (1-NP) to 1-naphthol and monitored by differential pulse voltammetry (DPV). Under optimum conditions, the amperometric signals increased linearly with the target DNA concentrations (10 pM to 1000 pM), and the DNA sensor exhibited a detection limit as low as 2.11 pM (S/N=3) with an excellent differentiation ability, and the proposed method showed acceptable stability and reproducibility. It has been applied for assay of BCR/ABL fusion gene from real samples with satisfactory results.


Chromatographic properties of hydrogenated microdiamond synthesized by high pressure and high temperature.
Adsorption and chromatographic properties of oxidized and hydrogenated 'high pressure and high temperature' synthesised diamond (HPHT) are studied using high-performance liquid chromatography. The retention factors of organic cation (benzyltributylammonium chloride), weak base (aniline), weak acid (benzoic acid), strong acid (benzenesulfonic acid), hydrophobic toluene, and hydrophilic uracil are obtained at varied pH, organic solvent content, and ionic strength of mobile phase. Both adsorbents exhibited moderate polarity with a mixed-mode retention mechanism with a combination of electrostatic, hydrophobic and hydrophilic interactions. Unexpectedly, hydrogenated HPHT revealed significant anion-exchange properties under acidic conditions and cation-exchange properties under alkaline conditions, while only cation-exchange selectivity was noted for oxidized HPHT across the enntire pH range. The retention factors obtained for a set of model compounds including n-alkyl-, polymethyl-, nitro- and halogenated benzenes correlated well with their hydrophobicity (logP) values. The thermal stability of the adsorbent and immutability of retention mechanisms involved was confirmed by linear van't Hoff plots for the investigated compounds.


Designing a DNA Vaccine-based Leishmania major Polytope (Preliminary Report).
Leishmaniasis is a neglected disease affecting millions of people worldwide. The treatment of the disease is hampered due to high cost, toxicity and the crisis of drug resistance. Polytope approaches of genetic immunization could be a strategy for prevention of infectious diseases. Furthermore, the identification of Leishmania genome sequence and the application of bioinformatics assist us to devise an effective vaccine's candidate. A linear sequence from predicted epitopes of GP63, LACK and CPC antigens was designed and was optimized using online available algorithms. The synthesized sequence (LAKJB93) was ligated to pEGFP-N1 plasmid. The 264bp sequence was cloned at N terminal of GFP into pEGFP_N1 expression vector and transfect into CHO cell line. Construct was efficient expressed in CHO cells. The protein of LAKJB93 cosnstruct was expressed in CHO cells successfully.


Control beliefs of the frail elderly. Assessing differences between homebound and nursing home residents.
Previous age-related sense of control studies have largely focused on active, community-dwelling aged individuals and have excluded elderly persons who are frail. This study compares sense of control and life satisfaction as determined through rating scale administration between two frail, dependent samples: nursing home residents and homebound elderly. Differences in control scores were statistically significant for those who were homebound expressing higher perceived personal control than nursing home residents (p < .001). Sense of control has no correlation with either life satisfaction or length of stay in the nursing home cohort.


[Effect of various doses of ethanol on the structure of the wakefulness-sleep cycle in cats].
I.p. administration of 25% ethanol solution with a gradual increase of the dose from 1 to 2 g/kg prolonged the wakefulness, reduced the slow-wave sleep, inhibited the paradoxical phase, and caused a fragmentation of the sleep-wakefulness cycle. The above disorders preserved during a few days after the cessation of ethanol administration.


Autonomic responses to pressure sensitivity of head, face and neck: Heart rate and skin conductance.
Subjective scales are frequently used in the design process of head-related products to assess pressure discomfort. Nevertheless, some users lack fundamental cognitive and motor abilities (e.g., paralyzed patients). Therefore, it is vital to find non-verbal measurements of pressure discomfort and pressure pain. This study gathered the autonomic response data (heart rate and skin conductance) of 30 landmarks in head, neck and face from 31 participants experiencing pressure discomfort and pressure pain. The results indicate that pressure stimulation can change heart rate (HR) and skin conductance (SC). SC can be more useful in assessing pressure discomfort than HR for specific landmarks, and SC also possesses a faster arousal rate than HR. Moreover, HR decreased in response to pressure stimulation, while SC decreased followed by an increase. In comparisons between genders, the subjective pressure discomfort threshold (PDT) and pressure pain threshold (PPT) of women were lower than those of men, but men's autonomic responses (HR and SC) were more intense. Furthermore, there was no linear correlation between subjective pressure thresholds (PDT and PPT) and autonomic response intensity. This study has significant implications for resolving ergonomic issues (pressure discomfort and pain) associated with head-related products.


The accumulation of heavy metals in agricultural land and the associated potential ecological risks in Shenzhen, China.
Accumulation of heavy metals in agricultural land and their ecological risks are key issues in soil security studies. This study investigated the concentrations of six heavy metals--copper (Cu), zinc (Zn), lead (Pb), nickel (Ni), and chromium (Cr) in Shenzhen's agricultural lands and examined the potential hazards and possible sources of these metals. Eighty-two samples from agricultural topsoil were collected. Potential ecological risk index was used to calculate the potential risk of heavy metals. Principal component analysis (PCA) was applied to explore pollution sources of the metals. Finally, Kriging was used to predict the spatial distribution of the metals' potential ecological risks. The concentrations of the heavy metals were higher than their background values. Most of them presented little potential ecological risk, except for the heavy metal cadmium (Cd). Four districts (Longgang, Longhua, Pingshan, and Dapeng) exhibited some degree of potential risk, which tended to have more industries and road networks. Three major sources of heavy metals included geochemical processes, industrial pollutants, and traffic pollution. The heavy metal Cd was the main contributor to the pollution in agricultural land during the study period. It also poses the potential hazard for the future. High potential risk is closely related to industrial pollution and transportation. Since the 1980s, the sources of heavy metals have evolved from parent rock weathering, erosion, degradation of organics, and mineralization to human disturbances resulting in chemical changes in the soil.


[Tryptamine as an endogenous modulator of neuronal sensitivity to serotonin].
Tryptamine has been studied for its effect on the 5-hydroxytryptamine-induced responses of the dorsal root ganglion neurons in rat with intracellular registration of the membrane potential and conductance and application of drugs from micropipettes under pressure. It was found that tryptamine applied in high concentrations acted like 5-hydroxytryptamine; but in the concentration range when it has no effect on the membrane potential and membrane conductance it either enhanced (10(-7) mol/l) or diminished (10(-5) mol/l) 5-hydroxytryptamine responses mediated by 5-HT1A- but not by 5-HT2-receptors. Harmane acted like tryptamine, but its derivatives either only enhanced or only inhibited the 5-hydroxytryptamine effects. The allosterical nature of 5-hydroxytryptamine-modulating action of tryptamine, harmane and its derivatives is discussed.


Proximal humerus fractures: A review of current practice.
The management of proximal humeral fractures (PHF) remains controversial. Its incidence is increasing. Patients should be meticulously assessed clinically for co-morbidities and neuro-vascular injuries. Radiological investigation helps provide information on the fracture configuration and dislocations. Enhanced by 3-dimensional CT scanning, these further help in decision making and operative planning. PHF classifications have been demonstrated to have poor intra-observer and inter-observer reliability. Research has identified some radiographic predictive factors for humeral head ischaemia and likely failure of surgical fixation. The range of management options include non-operative treatment, operative fixation, intramedullary nailing and arthroplasty (hemiarthroplasty, reverse shoulder replacement). The majority of PHFs are stable injuries and non-operative management is usually successful. Some degree of malunion is readily tolerated especially by elderly patients. Surgical management of significantly displaced, unstable proximal humerus fractures should aim to stabilise the fracture adequately and provide satisfactory function for the long term. Management of the greater tuberosity is pivotal for the eventual outcome. When fixation may appear to be compromised by poor bone quality, likely poor function, age related rotator cuff degeneration or likely humeral head ischaemia clinicians may opt for arthroplasty. Successful hemiarthroplasty outcomes are dependent on sufficient healing of the tuberosity and recovery of the rotator cuff integrity. Reverse shoulder replacement can predictably deliver good functional outcomes for the shoulder in elderly patients, where rotator cuff dysfunction is suspected or as a revision procedure following failure of other surgical interventions. As opposed to hemiarthroplasty, which has shown a downward trend, there has been an increasing trend towards the use of reverse shoulder replacement in proximal humeral fractures. The management of PHFs should be patient specific, fracture specific and meet the functional demands and needs of the individual patient. The surgeon's skill set and clinical experience also plays an important role in the options of management available.


Diagnosis of neonatal sepsis: the past, present and future.
Sepsis remains a significant cause of neonatal mortality and morbidity, especially in low- and middle-income countries. Neonatal sepsis presents with nonspecific signs and symptoms that necessitate tests to confirm the diagnosis. Early and accurate diagnosis of infection will improve clinical outcomes and decrease the overuse of antibiotics. Current diagnostic methods rely on conventional culture methods, which is time-consuming, and may delay critical therapeutic decisions. Nonculture-based techniques including molecular methods and mass spectrometry may overcome some of the limitations seen with culture-based techniques. Biomarkers including hematological indices, cell adhesion molecules, interleukins, and acute-phase reactants have been used for the diagnosis of neonatal sepsis. In this review, we examine past and current microbiological techniques, hematological indices, and inflammatory biomarkers that may aid sepsis diagnosis. The search for an ideal biomarker that has adequate diagnostic accuracy early in sepsis is still ongoing. We discuss promising strategies for the future that are being developed and tested that may help us diagnose sepsis early and improve clinical outcomes. IMPACT: Reviews the clinical relevance of currently available diagnostic tests for sepsis. Summarizes the diagnostic accuracy of novel biomarkers for neonatal sepsis. Outlines future strategies including the use of omics technology, personalized medicine, and point of care tests.


The application of abbreviated MRI protocols in malignant liver lesions surveillance.
Cancer is one of the leading public health problems globally. Since time is of the essence in oncology, the sooner an accurate diagnosis is made, the better the prognosis for patients. There is a growing need to find a flawless and fast imaging method for cancer detection, but also for its evaluation during treatment. In this respect, the possibilities and novelties of magnetic resonance imaging are particularly promising. Abbreviated magnetic resonance imaging (AMRI) protocols have aroused universal interest as a compromise between scanning time reduction and preservation of image quality. Shorter protocols focused on the detection of suspicious lesions with the most sensitive sequences could provide a diagnostic performance similar to the one of the standard protocol. The purpose of this article is to review the ongoing accomplishments in the use of AMRI protocols in liver metastases and HCC detection.


Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity.
As more data are generated from proteome and transcriptome analyses of snake venoms, we are gaining an appreciation of the complexity of the venoms and, to some degree, the various sources of such complexity. However, our knowledge is still far from complete. The translation of genetic information from the snake genome to the transcriptome and ultimately the proteome is only beginning to be appreciated, and will require significantly more investigation of the snake venom genomic structure prior to a complete understanding of the genesis of venom composition. Venom complexity, however, is derived not only from the venom genomic structure but also from transcriptome generation and translation and, perhaps most importantly, post-translation modification of the nascent venom proteome. In this review, we examine the snake venom metalloproteinases, some of the predominant components in viperid venoms, with regard to possible synthesis and post-translational mechanisms that contribute to venom complexity. The aim of this review is to highlight the state of our knowledge on snake venom metalloproteinase post-translational processing and to suggest testable hypotheses regarding the cellular mechanisms associated with snake venom metalloproteinase complexity in venoms.


Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of "autoimmune" hepatitis.
Sixty-five patients with histologically proven chronic active hepatitis of unknown cause but associated with the antiliver/kidney microsome antibody type 1, confirmed by immunofluorescence and immunoprecipitation, were selected as forming a special entity. This disease was found to be rare with a prevalence of 5/1,000,000. The female to male ratio was 8:1. The condition occurred at all ages but was most common between the ages of 2 and 14 years. In 22 of the 65 cases, the hepatitis was associated with an autoimmune disease, most commonly insulin-dependent diabetes, autoimmune thyroid disease and vitiligo. The same autoimmune diseases were present in first-degree relatives from seven families. In 36 cases, the onset of disease resembled acute viral hepatitis. Serum biochemical tests showed marked elevation in aminotransaminases and hypergammaglobulinemia. Paradoxically, serum and salivary IgA levels were often normal or low. Histologic findings were multifocal hepatic necrosis with bridging in the acute stage, and aggressive hepatitis with mononuclear cell infiltration or macronodular cirrhosis in the late stages. Serologically, apart from the presence of antiliver/kidney microsome antibody type 1, the disease was characterized by the absence of antiactin, antimitochondria and antinucleus antibodies; however, organ-specific autoantibodies were often present. The clinical course was usually severe: six patients in the acute stage presented with fulminant hepatitis, and all, except two, other patients progressed to cirrhosis. Prolonged treatment with corticosteroids and immunosuppressants was usually effective in rendering the cirrhosis inactive. The cumulative survival rate was 51% at 14 years. We propose to call this entity "anti-LKM1 chronic active hepatitis" or "autoimmune hepatitis type II" to differentiate it from classical "lupoid hepatitis" or autoimmune hepatitis type I.


A Case Report of Lung Transplantation After Hematopoietic Stem Cell Transplantation and Literature Review.
Pulmonary complications may occur after hematopoietic stem cell transplantation for hematologic malignancies. Lung transplantation is the only treatment option for end-stage lung failure. We presented a case of acute myeloid leukemia who received a hematopoietic stem cell transplantation and underwent bilateral lung transplantation with end-stage usual interstitial pneumonia and chronic obstructive lung disease. This case showed that lung transplantation could be successfully applied in properly selected hematologic malignancy patients with long disease-free survival, like lung transplantations performed for other indications.


In vivo human retinal swept source optical coherence tomography and angiography at 830 nm with a CMOS compatible photonic integrated circuit.
Photonic integrated circuits (PIC) provide promising functionalities to significantly reduce the size and costs of optical coherence tomography (OCT) systems. This paper presents an imaging platform operating at a center wavelength of 830 nm for ophthalmic application using PIC-based swept source OCT. An on-chip Mach-Zehnder interferometer (MZI) configuration, which comprises an input power splitter, polarization beam splitters in the sample and the reference arm, and a 50/50 coupler for signal interference represents the core element of the system with a footprint of only [Formula: see text]. The system achieves 94 dB imaging sensitivity with 750 [Formula: see text]W on the sample, 50 kHz imaging speed and 5.5 [Formula: see text]m axial resolution (in soft tissue). With this setup, in vivo human retinal imaging of healthy subjects was performed producing B-scans, three-dimensional renderings as well as OCT angiography. These promising results are significant prerequisites for further integration of optical and electronic building blocks on a single swept source-OCT PIC.


Geometry of intercalation of psoralens in DNA approached by molecular mechanics.
The results of molecular mechanical calculations on intercalation complexes of 3-carbethoxypsoralen, 5-methoxypsoralen, 8-methoxypsoralen, 7-methylpyrido[3,4-c]psoralen (MepyPs) and 7-methylpyrido[4,3-c]psoralen (2N-MePyPs) with the double stranded duodecanucleotide d(CGCGATATCGCG)2 are presented. In the energy-minimized structures, the psoralens are intercalated with their plane orthogonal to the helix axis. Stacking interactions between the furan ring of the psoralen and the adjacent bases are maximized in most derivatives studied, whereas the effect of the various substituents of the psoralen ring is to specifically push part of the molecule towards either the minor or the major groove, preventing a symmetrical intercalation (with respect to the two strands of the DNA). The relative position of the psoralen ring and of the adjacent thymine foreshadows the formation of furan-side monoadducts in 3-CPs, MePyPs and 2N-MePyPs, whereas the formation of a pyrone-side monoadduct appears as geometrically more favourable in 5-MOP and both furan- and pyrone-side monoadducts can be geometrically envisaged in 8-MOP. A good correlation therefore exists between the more or less favourable equilibrium geometries and the experimentally observed photoreactions. The present study is the first attempt to characterize the geometrical parameters as part of a complex set of geometrical, dynamical and excited state parameters governing the overall DNA-psoralen photoreaction.


Stabilization of gene expression and cell morphology after explant recycling during fin explant culture in goldfish.
The development of fin primary cell cultures for in vitro cellular and physiological studies is hampered by slow cell outgrowth, low proliferation rate, poor viability, and sparse cell characterization. Here, we investigated whether the recycling of fresh explants after a first conventional culture could improve physiological stability and sustainability of the culture. The recycled explants were able to give a supplementary cell culture showing faster outgrowth, cleaner cell layers and higher net cell production. The cells exhibited a highly stabilized profile for marker gene expression including a low cytokeratin 49 (epithelial marker) and a high collagen 1a1 (mesenchymal marker) expression. Added to the cell spindle-shaped morphology, motility behavior, and actin organization, this suggests that the cells bore stable mesenchymal characteristics. This contrast with the time-evolving expression pattern observed in the control fresh explants during the first 2 weeks of culture: a sharp decrease in cytokeratin 49 expression was concomitant with a gradual increase in col1a1. We surmise that such loss of epithelial features for the benefit of mesenchymal ones was triggered by an epithelial to mesenchymal transition (EMT) process or by way of a progressive population replacement process. Overall, our findings provide a comprehensive characterization of this new primary culture model bearing mesenchymal features and whose stability over culture time makes those cells good candidates for cell reprogramming prior to nuclear transfer, in a context of fish genome preservation.


Cloning and functional characterization of a carotenoid cleavage dioxygenase 2 gene in safranal and crocin biosynthesis from Freesia hybrida.
Safranal and crocin, commonly derived from the oxidative cleavage reaction of zeaxanthin in plants, are two kinds of apocarotenoids with versatile functions, which were only found in limited number of plant species. In this study, both metabolites were detected and varied concomitantly with the expression of carotenoid cleavage dioxygenase (CCD) genes in Freesia hybrida, Red River® and Ambiance cultivars. The newly isolated CCD, denoted here as FhCCD2, was phylogenetically clustered with other reported saffron CCD2s. Besides, ten introns were also observed in the genomic DNA sequence of FhCCD2 and the presence of N-terminal transporter peptide suggested its plastidial sub-localization. Biochemical analysis showed that the FhCCD2 cleaved zeaxanthin at the 7, 8 and 7', 8' double bonds to generate intermediates prerequisite for the biosynthesis of safranal and crocin. Further, gene transient expression analysis showed that the promoter of FhCCD2 was functional in Ambiance as well as Red River® cultivars, even with slight variation in their promoter sequence. At present, CCD2 proteins have only been found in Freesia and Crocus genus of Iridaceae family. Phylogenetic and intron position analysis infer that CCD2 perhaps emerged after the intron loss during evolutionary process of CCD1 or their shared ancestry.


Correction: Role of MicroRNA 1207-5P and Its Host Gene, the Long Non-Coding RNA Pvt1, as Mediators of Extracellular Matrix Accumulation in the Kidney: Implications for Diabetic Nephropathy.
[This corrects the article DOI: 10.1371/journal.pone.0077468.].


Monocyte/Lymphocyte Ratio and MCHC as Predictors of Collateral Carotid Artery Disease-Preliminary Report.
Carotid artery disease accounts for 30% of ischemic strokes in the general population. Numerous biomarkers have been investigated for predicting either the progression or the severity of the disease. The aim of this retrospective study was to compare hematologic indices among patients referred for surgical interventions due to severe carotid disease. In total, 135 patients (87 (64.4%) men and 48 (35.6%) women) with a mean age of 70 ± 8 years who underwent surgical carotid intervention were enrolled into the study. A Mann-Whitney test for independent samples revealed significant differences in monocyte to lymphocyte ratio (MLR) and mean corpuscular hemoglobin concentration (MCHC) between patients with one and two (collateral) carotid diseases. The cut-off value for MLR was 0.3 (AUC = 0.654, p = 0.048, 70.0% sensitivity and 74.6% specificity) and for MHCH was 21.6. (AUC = 0.730, p < 0.001, 70.0% sensitivity and 77.2% specificity). A multivariable model of logistic regression revealed two significant parameters for collateral carotid stenosis disease including MLR > 0.3 (OR 6.19 with 95% CI 2.02-19.01, p = 0.001) and MCHC > 21.6 (OR 7.76, 95% CI 2.54-23.72, p < 0.001). MLR above 0.3 and MCHC above 21.6 have predictive values for colleterial carotid stenosis and may be used as easily accessible indicators for atherosclerosis severity.


Study of a floating fraction obtained during preparation of myelin from degenerating goldfish optic tract.
A floating fraction that layers on top of 0.25 sucrose has been obtained during the preparation of myelin from intact and 9 day degenerating goldfish optic tracts. The proportion of total tract protein isolated in floating fraction rises from 6.6% to 11.0% during degeneration. This increase is paralleled by a morphologically observed splitting of myelin lamellae. Floating fraction contains all of the major myelin proteins but shows a 40% increase in the proportion of basic protein and a 2-3 fold decrease in the proportion of IP proteins (intermediate molecular weight glycoproteins) and a 36 Kd (X) protein. The lipid to protein ratio is slightly higher in floating fraction than myelin. Lipid composition is characterized by 1/2-1/3 the myelin levels of galactolipids and twofold increased levels of triglycerides and cholesterol esters. Electron microscopy of floating fraction shows a mixture of myelin fragments with few lamellae and single membrane fragments. Taken together the results indicate that floating fraction in the degenerating goldfish optic tract is at least partially derived from the breakdown of myelin.


[Endothelin signaling in cardiac myocyte].
Endothelin can affect the contractile properties of cardiacmyocyte, stimulate myocyte growth and myofibrillogenesis, and increase resistance to apoptosis by intracellular signaling pathways. This article briefly reviews the regulative effects of these signaling pathways including protein kinase C, mitogen activated protein kinase, and phosphoinositide 3'-OH kinase/protein kinase B.


Neurotoxicologic examination of rats exposed to 1,1,1-trichloroethane vapor for 13 weeks.
Large evoked potential and EEG changes occurred in a pilot study in Fisher 344 rats during exposure to 2000 ppm of 1,1,1-trichloroethane (1,1,1-T; a cleaning solvent with anesthetic properties). In the main study, rats were evaluated for persistent nervous system effects the week following exposure to 0, 200, 630, or 2000 ppm 1,1,1-T for 6 h/day, 5 days/week, for 13 weeks. Rats were clinically examined regularly and were given a functional observational battery monthly (FOB, including forelimb and hindlimb grip performance testing). After 13 weeks of exposure, the rats were evaluated by FOB and by visual, auditory, somatosensory, and caudal nerve-evoked potentials. After functional testing, a subgroup of rats had histopathologic examination of brain, spinal cord, peripheral nerves, and limb muscles. There were no post-exposure treatment-related findings in any parameter (FOB observations plus 39 dependent variables) except for a slightly smaller forelimb grip performance in the 2000-ppm exposure group. There was no recognized toxicologic significance for the difference in forelimb grip performance; a lack of findings in any other clinical, evoked potential or morphologic parameter did not support a diagnosis of neurotoxicity.


Selection of internalization-deficient cells by interleukin-2-Pseudomonas exotoxin chimeric protein: the cytoplasmic domain of the interleukin-2 receptor beta chain does not contribute to internalization of interleukin-2.
To study the structural basis of ligand-induced receptor-mediated internalization of interleukin-2 (IL-2), a strategy has been developed to generate variant T cells that are deficient in internalization of this cytokine. IL-2 receptor (IL-2R) alpha- and beta-bearing EL4 cells, that express high-affinity IL-2R and internalize IL-2, were treated with low doses of IL-2-Pseudomonas exotoxin chimeric protein (IL-2-PE40). This treatment resulted in isolation of a variant (CX1) that was unable to express high-affinity IL-2R or internalize IL-2. Transfection of CX1 with the IL-2R beta cDNA led to surface expression of IL-2R beta and high-affinity IL-2R as well as the ability to internalize IL-2. This finding indicates that the absence of the beta subunit was the sole defect in CX1 responsible for its failure to internalize IL-2. By transfecting CX1 with mutated beta cDNA, several CX1 transfectants were produced that expressed a beta-subunit that lacked all amino acids of the intracytoplasmic region. These transfectants expressed high-affinity IL-2R and internalized IL-2 at a rate comparable to cells expressing wild-type beta-chain. These results demonstrate that internalization of IL-2 is independent of any signals contained in the intracytoplasmic tail of the beta subunit and raise the possibility that such signals may be entirely contained within the gamma subunit.


RETRACTED: Six different hemofiltration devices for blood conservation in cardiac surgery.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor. Reason: By comparing the results of this article with results reported by Berend Fedderson (Hämofiltration als blutsparendes Verfahren in der Herzchirurgie: sechs verschiedene Hämofilter im Vergleich; Niebüll, Germany; http://d-nb.info/930239350), it has been determined that experimental outcomes have been altered. Thus, the research published in this article was misrepresented to The Annals of Thoracic Surgery and the article should be retracted from the scientific record.


Training adult laypeople in basic life support. A systematic review.
Bystander assistance is decisive to enhance the outcomes of out-of-hospital cardiac arrest. Despite an increasing number of basic life support (BLS) training methods, the most effective formula remains undefined. To identify a gold standard, we performed a systematic review describing reported BLS training methods for laypeople and analyzed their effectiveness. We reviewed the MEDLINE database from January 2006 to July 2018 using predefined inclusion and exclusion criteria, considering all studies training adult laypeople in BLS and performing practical skill assessment. Two reviewers independently extracted data and evaluated the quality of the studies using the MERSQI (Medical Education Research Study Quality Instrument) scale. Of the 1263 studies identified, 27 were included. Most of them were nonrandomized controlled trials and the mean quality score was 13 out of 18, with substantial agreement between reviewers. The wide heterogeneity of contents, methods and assessment tools precluded pooling of data. Nevertheless, there was an apparent advantage of instructor-led methods, with feedback-supported hands-on practice, and retraining seemed to enhance retention. Training also improved attitudinal aspects. While there were insufficiently consistent data to establish a gold standard, instructor-led formulas, hands-on training with feedback devices and frequent retraining seemed to yield better results. Further research on adult BLS training may need to seek standardized quality criteria and validated evaluation instruments to ensure consistency.


Peripheral iridectomy for atraumatic haptic externalization in large eyes having anterior sclerotomy for glued intraocular lens.
We describe a simple technique of vitrector-assisted peripheral iridectomy performed along the base of the scleral flap and beneath a corneal mark at the 180-degree axis for atraumatic haptic externalization in large eyes having glued intrascleral haptic fixation of an intraocular lens (IOL). Anterior sclerotomy is often performed in large eyes, which shifts the IOL plane anteriorly, often leading to peripheral iris damage during the anterior sclerotomy or haptic externalization. The vitrector-assisted peripheral iridectomy helps to prevent iatrogenic iris tissue damage during the surgical procedure. Neither author has a financial or proprietary interest in any material or method mentioned.


Corrigendum to "Empathy and the Medical Student House Call: The Effect of Clinical Settings on Empathy in Third Year Medical Students".
[This corrects the article DOI: 10.1177/23821205231175804.].


Collaborative practice: matching staff skills to patient needs and checking baseline staffing levels.
Vancouver Coastal Health uses a collaborative practice process to enable nursing units to be proactive and adapt quickly to changing patient population needs using a standardized and integrated approach. The process involves clinical directors, frontline managers, staff, and union representatives from the outset and is based on a registered nurse/licensed practical nurse/patient care aide collaborative model of practice. Results show a total return on investment in 2.4 years.


[Animal experimental study with different suture materials in colonic anastomosis in rats].
On colon anastomoses of the rat four different suture materials were tested under standardized conditions. The tensile strength was determined by means of a microtraction apparatus. As a result it became evident that there are significant differences in the behaviour of the various suture guts.


Kidney delayed graft function after combined kidney-solid organ transplantation: A review.
Kidney delayed graft function (K-DGF) is a common post-kidney transplant complication associated with adverse outcomes. With continued advances in solid organ transplantation (SOT), combined kidney-solid organ transplantation (CKSOT) is an ever-growing transplant option for patients with advanced kidney disease in the setting of concurrent solid organ failure. K-DGF in this setting is understudied. In this review, we aimed to abridge the representative literature on K-DGF in CKSOT. K-DGF occurs at different rates across combined and sequential kidney-solid organ transplantation (SKSOT), in simultaneous-pancreas kidney (SPK) transplant (8-23%), simultaneous heart-kidney (SHK) transplant (27-37%), simultaneous-liver kidney (SLiK) transplant (16-49%), and kidney after thoracic (13.6-19.2%) and abdominal (13.6-25%) transplantation. Though many K-DGF risk factors span across various subtypes of combined KSOT, some effect particular transplant types more specifically and may be modifiable to reduce K-DGF incidence. While more studies are needed to prevent and manage K-DGF in combined kidney-solid organ transplantation, we hope our review will provide context of this disease and spur further inquiry.


[Increased piglet losses upon exudative epidermitis - a case report].
A massive outbreak of exudative epidermitis (EE) occurred on a Western German piglet producing farm with 350 productive sows. Gilts are produced on site. In one group of piglets, more than 50% of suckling and nursery piglets were clinically affected; furthermore, gilts as well as sows showed localized blackish-squamous skin lesions in the neck area. Generalized infection in suckling and nursery piglets resulted in mortality rates of up to 10% per weaning group. Swabs of moist, affected areas of skin taken on the farm in addition to swab and organ samples collected during necropsy were examined via bacterial cultivation. Both Staphylococcus (St.) hyicus and St. chromogenes strains were detected in affected skin lesions, with St. hyicus also present in systemic localizations. Further characterization of the St. hyicus strains identified ExhA and SHETA as toxins involved, and isolates showed resistance to penicillin and aminopenicillin. In the short term, antibiotic treatment with trimethoprim-sulfadiazine of the whole age group combined with individual treatment of severely affected animals as well as washing with an iodine-containing solution improved the clinical signs. In order to reduce the antibiotic use, an autogenous vaccine against the isolated St. hyicus and St. chromogenes strains for gilts and sows was produced and applied as a basic immunization twice before farrowing. In addition, external and internal biosecurity was evaluated and adjusted using an objective questionnaire (Bio-check.UGentTM). The combination of taken measures resulted in a long-term improvement of the overall health status. Several months after the severe EE outbreak, the sporadic occurrence of new EE cases in individual piglets could be controlled by the adjustment of the autogenous vaccine with an additional St. hyicus isolate. The case report illustrates how the combination of continuous monitoring, individual and group antibiotic treatment, biosecurity evaluation, and the use of appropriate immune prophylaxis can improve the clinical picture of EE.


Pharmacogenetics of asthma controller treatment.
The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability. The goal of the present study was to identify novel variants that associate with response to common asthma controllers: fluticasone, combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms (SNPs) in β2-adrenergic receptor, corticosteroid and leukotriene pathway candidate genes. Participants in a large clinical trial of step-down strategies volunteered for this pharmacogenetic study. A total of 169 SNPs in 26 candidate genes were genotyped in 189 Caucasian participants with asthma who took either fluticasone (100 μg bid), fluticasone propionate (100 μg) + salmeterol (50 μg) (FP/Salm) or montelukast (5 or 10 mg) each night for 16 weeks. Primary outcomes were the slopes of plots of Asthma Control Questionnaire (ACQ) scores versus time following randomization; and the percent change in percent predicted FEV1 (ΔFEV1%pred) from enrollment to the end of the study. Associations between SNPs and outcomes were analyzed using general linear models. False discovery rate and Bonferroni corrections were used to correct for multiple comparisons. In all, 16 SNPs in seven genes were significantly associated with outcomes. For FP/Salm, three SNPs in CHRM2 associated with ACQ slope (P=2.8 × 10⁻⁵), and rs1461496 in HSPA8 associated with ΔFEV1%pred. For fluticasone, five SNPs in CRHR1 (P=1.9 × 10⁻⁴), and three SNPs in COL2A1 associated with ACQ slope and ΔFEV1%pred, respectively. For montelukast, four SNPs in CHRM2 associated with ΔFEV1%pred and predicted an opposite effect compared with fluticasone (P=9 × 10⁻³). The present study indentified several novel SNPs that associate with response to common asthma controllers, and support further pharmacogenomic study and the use of genetic variants to personalize asthma treatment.


Endogenous IGFBP-3 regulates excess collagen expression in intestinal smooth muscle cells of Crohn's disease strictures.
Stricture formation occurs in ≈30% of patients with Crohn's disease (CD) and is a significant cause of morbidity. Strictures are characterized by intestinal smooth muscle cell hyperplasia, smooth muscle cell hypertrophy, and fibrosis due to excess net extracellular matrix production, including collagen. Transforming growth factor-β1 (TGF-β1) has profibrotic effects in many tissues due to its ability to regulate collagen expression and extracellular matrix dynamics. We previously showed that both insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) and TGF-β1 are expressed by normal human intestinal smooth muscle cells, bind to, and activate TGF-βRII/I receptors in these cells. Smooth muscle cells isolated from the muscularis propria of patients were used to prepare RNA, protein lysates, or placed into primary culture. IGFBP-3, TGF-β1, and collagen IαI expression was measured with quantitative reverse-transcription polymerase chain reaction (RT-PCR) and protein levels by enzyme-linked immunosorbent assay (ELISA) or immunoblot. Expression and production of IGFBP-3, TGF-β1, and collagen IαI were significantly increased specifically in smooth muscle cells isolated from regions of strictured intestine in CD compared to nonstrictured histologically normal resection margin. IGFBP-3 and TGF-β1 regulated collagen IαI expression and production via a TGF-βRII/I-dependent and Smad2/3-dependent mechanism. Upregulated (excess) collagen IαI expression and production in smooth muscle cells of strictures and basal collagen IαI in smooth muscle cells of normal margin were inhibited by immunoneutralization of IGFBP-3 or TGF-β1. The findings indicate that upregulated endogenous IGFBP-3 and TGF-β1 expression regulates excess collagen IαI production and contributes to fibrosis and stricture formation in CD.


Decrease in the levels of specific non-polysomal messenger ribonucleoproteins during the mouse sarcoma-180 ascites cell cycle.
A few mRNAs in S-180 ascites cells are found as non-polysomal messenger ribonucleoprotein particles, whose translation is restricted both in vivo and in vitro. To determine if these mRNPs remain untranslated throughout the cell cycle we obtained S-180 ascites cells enriched in cell cycle stages by centrifugation through ficoll gradients. The "inactive" mRNA species were clearly present in the pre-polysomal fraction from S and pre-S phase cells, however they were not detected in the mRNP fraction from post S phase cells. Hybridization of a cloned cDNA probe for one of these species (P-40) to polysomal RNA from pre- or post-S phase cells demonstrated it was present in substantially higher concentrations in polysomes from post-S phase cells, consistent with its translation after S phase. We also observed that a poly (A)-minus form of the mRNA coding for actin was restricted to post S phase cells.


A simple method for identifying image orientation of chest radiographs by use of the center of gravity of the image.
Bedside chest radiography is a frequent X-ray examination when patients are physically incapacitated. An X-ray cassette with an imaging plate is inserted below the patient's body, and the image orientation of the radiograph is determined by the direction of insertion. Therefore, an incorrect direction of insertion would yield an incorrect image orientation for diagnosis, if no correction was performed on the resulting image data. We aimed to develop a computerized method that identifies the image orientation of chest radiographs by using the center of gravity (COG) of the images in terms of pixel values. To develop the computerized method, we used 247 chest images contained in the Japanese Society of Radiological Technology database as training cases, and 1833 bedside chest radiographs obtained in our institution for validation testing. As a result for the 247 training images, the angles which were obtained from directions between the COG of pixel values and the center of the image were distributed between 162.7° and 224.4° in a clockwise direction. We used the angle of the COG to identify the correct view orientation. The range of angles (139.1°-229.0°) for the COG in the chest image with correct image orientation was determined with a 99 % confidence interval for the angles of the COGs obtained from the training images. As a result of the validation test based on the range of angles determined, 99.7 % of the 1833 test images were identified correctly.