Genital aphthosis in Behçet's disease: is it associated with less eye involvement?
Behçet's disease (BD) is a multisystem disease classified among the vasculitides with various clinical features. Genital aphthosis (GA) is one of the major manifestations of BD. The aim of this study was to evaluate the characteristics of BD patients with GA. A cross-sectional sample of BD patients registered in 37 years was selected. We determined clinical and laboratory features of BD patients with GA (GA cases) and compared them with the patients who never developed GA (non-GA cases). The comparisons were performed by the chi-square test and logistic regression analysis. Odds ratios (ORs) with 95 % confidence intervals were calculated to estimate the precision of ORs. Among 6,935 BD patients, 4,489 cases (64.7 %) were ascribed to GA cases. Male to female ratio (1.11:1.00 vs. 1.48:1.00 OR 0.753, P value <0.001) and mean age of disease onset (OR = 0.9, P value <0.001) were lower in GA subset. In GA cases, oral aphthosis (OA) was a more common onset manifestation (OR 2.250, P value <0.001), while uveitis (OR 0.140, P value <0.001) and retinal vasculitis (OR 0.077, P value <0.001) were less common at the disease onset. In the whole course of disease, eye involvement was less common in GA cases (OR 0.215, P value <0.001). On the contrary, OA (OR 19.698, P value <0.001), skin (OR 1.762, P value <0.001), joint (OR 1.257, P value = 0.001), gastrointestinal (OR 1.302, P value = 0.009), neurological (OR 1.624, P value <0.001) and vascular involvements (OR 1.362, P value <0.001), epididymitis (OR 1.596, P value <0.001), positive pathergy test (OR 1.209, P value <0.001) and positive familial history of OA (OR 1.325, P value <0.001) were more common in GA subset. This study showed that GA subset of BD is associated with less eye involvement but higher rates of other BD manifestations.


Analysis of the promoters for the beta-esterase genes associated with insecticide resistance in the mosquito Culex quinquefasciatus.
Resistance to organophosphorus (OP) insecticides in the mosquito Culex quinquefasciatus is primarily due to the amplification and over-expression of non-specific esterases. Co-amplification of two esterase genes, estalpha2(1) and estbeta2(1), is the most common resistance genotype. In both resistant and susceptible mosquitoes the alpha- and beta-esterase genes are oriented in a head-to-head arrangement, the intergenic sequences containing promoter elements for the divergent transcription of both esterases. Transient transfection of luciferase reporter gene constructs into a C. quinquefasciatus cell line was used to study these promoters. A control vector was constructed with the strong Drosophila actin 5c promoter driving expression of beta-galactosidase. The beta-esterase promoters from both insecticide resistant and -susceptible insects were highly active in directing luciferase expression. Transfections with panels of deletions revealed several regions where binding sites for positive and negative regulatory elements are located, and candidate transcription factor sites have been identified. Gel shift assays have identified one DNA-protein interaction that is stronger with the resistant than with the equivalent but slightly altered susceptible sequence. The arthropod initiator site TCAGT 135bp upstream of the ATG in both beta-esterase promoters is essential for transcription initiation, but a putative TATA box is not involved.


99mTc-PSMA SPECT/CT Versus 68Ga-PSMA PET/CT in the Evaluation of Metastatic Prostate Cancer.
99mTc-prostate-specific membrane antigen (PSMA) SPECT/CT is less expensive and readily available modality compared with 68Ga-PSMA PET/CT for imaging prostate cancer (PC). The aim of this study is to compare the value of these 2 modalities in patients confirmed or suspicious to have metastatic prostate cancer. Twenty-two patients with the mean age of 66.6 ± 10.1 years were studied using 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT, with less than 7 days interval between the 2 imaging procedures. Whole-body PET/CT was done 60 minutes after IV injection of 185 MBq (5 mCi) of 68Ga-PSMA. 99mTc-PSMA SPECT/CT was performed 3 hours after IV injection of 555 to 740 MBq (15-20 mCi) of 99mTc-PSMA. The images of each modality were interpreted independently, and the results were compared according to patient-based as well as region-based analyses. In patient-based evaluation, both 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT scans were positive in 95.45% (21/22). In region-based evaluation, 68Ga-PSMA PET/CT detected 53 regions (median of 2 regions per patient; range, 0-5), whereas 43 (median of 2 regions per patient; range, 0-5) were detected by 99mTc-PSMA SPECT/CT. Most of these differences could be explained by lower detection rate of 99mTc-PSMA SPECT/CT in prostate bed (n = 6). PET/CT detected more involved regions than SPECT/CT (P = 0.007), whereas similar frequency of extraprostatic lesions were diagnosed in both modalities (P = 0.102). Significant correlation was also demonstrated between serum prostate-specific antigen level and imaging parameters of disease extension detected by 2 modalities. 99mTc-PSMA SPECT/CT could be a potential substitute for 68Ga-PSMA PET/CT in high-risk patients, except when evaluation of prostate bed is of major concern.


Hamartomatous polyposis syndromes.
Hamartomas are tumour-like malformations, consisting of disorganized normal tissues, typical of the site of tumour manifestation. Familial manifestation of hamartomatous polyps can be noted in juvenile polyposis syndrome (JPS), Peutz-Jeghers' syndrome (PJS), hereditary mixed polyposis syndrome (HMPS) and PTEN hamartoma tumour syndrome (PHTS). All the aforementioned syndromes are inherited in an autosomal dominant manner and form a rather heterogenous group both in respect to the number and localization of polyps and the risk of cancer development in the alimentary tract and other organs. Individual syndromes of hamartomatous polyposis frequently manifest similar symptoms, particularly during the early stage of the diseases when in several cases their clinical pictures do not allow for differential diagnosis. The correct diagnosis of the disease using molecular methods allows treatment to be implemented earlier and therefore more effectively since it is followed by a strict monitoring of organs that manifest a predisposition for neoplastic transformation.


A selective inhibitor reveals PI3Kγ dependence of T(H)17 cell differentiation.
We devised a high-throughput chemoproteomics method that enabled multiplexed screening of 16,000 compounds against native protein and lipid kinases in cell extracts. Optimization of one chemical series resulted in CZC24832, which is to our knowledge the first selective inhibitor of phosphoinositide 3-kinase γ (PI3Kγ) with efficacy in in vitro and in vivo models of inflammation. Extensive target- and cell-based profiling of CZC24832 revealed regulation of interleukin-17-producing T helper cell (T(H)17) differentiation by PI3Kγ, thus reinforcing selective inhibition of PI3Kγ as a potential treatment for inflammatory and autoimmune diseases.


The role of 1,3-propanediol production in fermentation of glycerol by Clostridium pasteurianum.
Waste crude glycerol from biodiesel production can be used to produce biobutanol using Clostridium pasteurianum with the main products being n-butanol, 1,3-propanediol (PDO) and ethanol. There has been much discrepancy and mystery around the cause and effect of process parameters on the product distribution, thus a better understanding of the pathway regulation is required. This study shows that as process pH decreased, the rate of cell growth and CO2 production also decreased, resulting in slower fermentations, increased duration of butanol production and higher butanol concentrations and yields. The production rate of PDO was multi-modal and the role of PDO appears to function in redox homeostasis. The results also showed that C. pasteurianum displayed little biphasic behavior when compared to Clostridia spp. typically used in ABE fermentation due to the alternative glycolysis-independent reductive pathway of PDO production, rendering it suitable for a continuous fermentation process.


Computer modeling of visual impairment caused by intraocular lens misalignment.
To evaluate a computer program to modulate the visual impairment caused by intraocular lens (IOL) misalignment and visualize results obtained by numerical calculations. Department of Ophthalmology, Medical Faculty of Charles University, Prague, Czech Republic. The optic imagery of a Landolt circle was calculated using a ray-tracing computer program. Visual aberrations resulting from a decentered and/or tilted IOL were studied using this program and compared with theoretical calculations. The IOL decentration and/or tilt shifted the postoperative refractive errors toward myopia and astigmatism (oblique). The combination of IOL decentration and tilt produced a refractive error that depended on the relationship between the geometrical axes of the decentration and tilt. The refractive error can be enhanced or diminished depending on the relationship of these axes. These findings verify the results calculated by paraxial vergence equations. A ray-tracing program simulated the optic imagery for various kinds of IOL misalignment and IOL optic properties.


Effect of human macrophage colony-stimulating factor on granulopoiesis and survival in bone-marrow-transplanted mice.
Human macrophage colony-stimulating factor (hM-CSF) has been isolated from normal human urine and purified to a homogeneous protein. The effect of hM-CSF on granulopoiesis was investigated in BALB/c mice transplanted with a suboptimal number of bone marrow cells. Lethally irradiated (7.8 Gy) mice were transplanted with 1 x 10(6) syngeneic mouse bone marrow cells and treated with a daily intraperitoneal dose of 64 micrograms/kg of hM-CSF for 5 days following the transplant. The hM-CSF injection resulted in stimulation of the recovery of blood neutrophils as well as an increase in the number of granulocyte-macrophage progenitor cells (CFU-GM) in the femur and spleen. The survival of lethally irradiated mice was dependent on the cell number transplanted; most mice transplanted with 2 x 10(4) cells died within 2 weeks. The recovery of hematopoiesis in mice transplanted with 2 x 10(4) cells was modestly but significantly stimulated by hM-CSF administration initiated from 5 days before or 1 day after transplantation for a 5-day period. Furthermore, the hM-CSF administrations markedly reduced the mortality in these mice during the early period after the transplantation. Since anaerobic bacteria were frequently detected in arterial blood immediately before the deaths but were not found in the surviving mice, it is speculated that early deaths occurring within 2 weeks after the transplant may be caused by opportunistic infections, and hM-CSF injection may prevent these mortal infections through its stimulating effect on monocyte-macrophage functions that are responsible for the production of hematopoietic regulators.


Glucose Variability and β- Cell Response by GLP-1 Analogue added-on CSII for Patients with Poorly Controlled Type 2 Diabetes.
The effects of twice-daily GLP-1 analogue injections added on continuous subcutaneous insulin infusion (CSII) in patients with poorly controlled type 2 diabetes (T2DM) were unknown. After optimization of blood glucose in the first 3 days by CSII during hospitalization, patients with poorly controlled T2DM were randomized to receive CSII combined with injections of exenatide or placebo for another 3 days. A total of 51 patients (30 in exenatide and 21 in placebo groups) with mean A1C 11% were studied. There was no difference in mean glucose but a significant higher standard deviation of plasma glucose (SDPG) was found in the exenatide group (50.51 ± 2.43 vs. 41.49 ± 3.00 mg/dl, p = 0.027). The improvement of incremental area under the curve (AUC) of glucose and insulinogenic index (Insulin 0-peak/ Glucose 0-peak) in 75 g oral glucose tolerance test was prominent in the exenatide group (p < 0.01). The adiponectin level was significantly increased with exenatide added on (0.39 ± 0.32 vs. -1.62 ± 0.97 μg/mL, in exenatide and placebo groups, respectively, p = 0.045). In conclusion, the add-on of GLP-1 analogue to CSII increased glucose variability and the β - cell response in patients with poorly controlled T2DM.


Dopamine induces glutamate accumulation in astrocytes to disrupt neuronal function leading to pathogenesis of minimal hepatic encephalopathy.
Minimal hepatic encephalopathy (MHE) is induced by elevated intracranial dopamine (DA). Glutamate (Glu) toxicity is known to be involved in many neurological disorders. In this study, we investigated whether DA increased Glu levels and collaborated with Glu to impair memory. We found that DA upregulated TAAR1, leading to reduced EAAT2 expression and Glu clearance in primary cortical astrocytes (PCAs). High DA increased TAAR1 expression, and high Glu increased AMPAR expression, inducing the activation of CaN/NFAT signaling and a decrease in the production of BDNF (Brain Derived Nerve Growth Factor)/NT3 (neurotrophin-3) in primary cortical neurons (PCNs). DA activated TAAR1 to downregulate EAAT2 and increase extracellular Glu levels in MHE. Additionally, DA together with Glu caused decreased production of neuronal BDNF/NT3 and memory impairment through the activation of CaN/NFAT signaling in MHE. From these findings, we conclude that DA increases Glu levels via interaction with TAAR1 and disruption of EAAT2 signaling in astrocytes, and DA interacting with TAAR1 and Glu interacting with AMPAR synergistically decreased the production of BDNF by activation of CaN/NFAT signaling to impair memory in MHE rats.


Abdominal Wall Defects: A Review of Current Practice Guidelines.
The 2 most common congenital abdominal wall defects are gastroschisis and omphalocele. Gastroschisis is a defect in the abdominal wall with exposed abdominal contents. Mortality rates are low but lengths of stay are often prolonged by bowel dysmotility and other intestinal abnormalities in complicated cases. Omphalocele is a defect through the umbilical cord with herniated abdominal contents covered by a sac. It is associated with other genetic abnormalities and other anomalies that can lead to significant morbidity and mortality. Prenatal diagnosis in both conditions allows for improved prenatal consultation and coordinated perinatal care to improve clinical outcomes.


Visual memory for agents and their actions.
Humans spend a considerable amount of time remembering other individuals' actions. Nevertheless, it is unclear how the visual system stores information about the identities of agents and their actions. To address this, I used a change detection method where observers were asked to remember agents and the actions they performed. Results show that observers can maintain information about both 2-3 agents and 2-3 actions simultaneously. However, they are highly impaired for remembering which agent performed which action, indicating that agent and action information are retained separately in visual working memory. Further experiments show that agent and action information can be bound together when the visual input contains the appropriate cues. However, this binding process significantly reduces the total amount of information that can be retained. Together, these results show that (1) an additional, resource-demanding process is needed to integrate agent and action information stored in separate working memory stores, and (2) the extent to which these two types of information are bound into integrated units depends largely on the presence of specific cues in the visual input.


Prevalence of Gout in the Surviving United States Solid Organ Transplantation Population.
Although incidence and survival are frequent topics within the solid organ transplantation (SOT) literature, the size of the surviving SOT population is not well known. Existing studies of gout in patients with SOT have focused on the incident SOT population. This analysis was performed to characterize the prevalent SOT population and the prevalence of gout within it. This study includes the 2017 United States (US) population size of recipients of kidney, heart, liver, and lung transplants that was estimated by combining primary transplant recipient cohort sizes (1988-2017) with previously published survival rates for each annual cohort's time since transplantation (0-29 years). Gout among prevalent patients with SOT was assessed using Medicare and commercial claims. A total of 637,231 US patients received a primary kidney (393,953), liver (142,186), heart (66,637), or lung (34,455) transplant between 1988 and 2017. An estimated 356,000 (55.8%) recipients were alive in 2017 (233,000 kidney; 78,700 liver; 29,300 heart; 14,700 lung). Gout was identified in 11% of prevalent patients with SOT in 2016. Higher rates of gout were seen in recipients of kidney (13.1%) and heart (12.7%) compared to recipients of liver (6.7%) and lung (5.6%) (P < .0001 in both datasets). Active diagnosed gout prevalence in the US population without a SOT history was 1.1% in 2016. Hundreds of thousands of US patients are living with a transplanted organ today and these numbers are likely to increase. In patients with SOT, gout is a frequent comorbidity of which physicians should be aware. This study suggests a markedly higher rate of gout among transplant recipients compared to the general US population.


Projections of the transmission of the Omicron variant for Toronto, Ontario, and Canada using surveillance data following recent changes in testing policies.
At the end of 2021, with the rapid escalation of COVID19 cases due to the Omicron variant, testing centers in Canada were overwhelmed. To alleviate the pressure on the PCR testing capacity, many provinces implemented new strategies that promote self testing and adjust the eligibility for PCR tests, making the count of new cases underreported. We designed a novel compartmental model which captures the new testing guidelines, social behaviours, booster vaccines campaign and features of the newest variant Omicron. To better describe the testing eligibility, we considered the population divided into high risk and non-high-risk settings. The model is calibrated using data from January 1 to February 9, 2022, on cases and severe outcomes in Canada, the province of Ontario and City of Toronto. We conduct analyses on the impact of PCR testing capacity, self testing, different levels of reopening and vaccination coverage on cases and severe outcomes. Our results show that the total number of cases in Canada, Ontario and Toronto are 2.34 (95%CI: 1.22-3.38), 2.20 (95%CI: 1.15-3.72), and 1.97(95%CI: 1.13-3.41), times larger than reported cases, respectively. The current testing strategy is efficient if partial restrictions, such as limited capacity in public spaces, are implemented. Allowing more people to have access to PCR reduces the daily cases and severe outcomes; however, if PCR test capacity is insufficient, then it is important to promote self testing. Also, we found that reopening to a pre-pandemic level will lead to a resurgence of the infections, peaking in late March or April 2022. Vaccination and adherence to isolation protocols are important supports to the testing policies to mitigate any possible spread of the virus.


G-quadruplex Structures Contribute to Differential Radiosensitivity of the Human Genome.
DNA, the fundamental unit of human cell, generally exists in Watson-Crick base-paired B-DNA form. Often, DNA folds into non-B forms, such as four-stranded G-quadruplexes. It is generally believed that ionizing radiation (IR) induces DNA strand-breaks in a random manner. Here, we show that regions of DNA enriched in G-quadruplex structures are less sensitive to IR compared with B-DNA in vitro and inside cells. Planar G-quartet of G4-DNA is shielded from IR-induced free radicals, unlike single- and double-stranded DNA. Whole-genome sequence analysis and real-time PCR reveal that genomic regions abundant in G4-DNA are protected from radiation-induced breaks and can be modulated by G4 stabilizers. Thus, our results reveal that formation of G4 structures contribute toward differential radiosensitivity of the human genome.


Neuropeptide Y: a potential theranostic biomarker for diabetic peripheral neuropathy in patients with type-2 diabetes.
Diabetic peripheral neuropathy (DPN), the most common microvascular complication of type-2 diabetes mellitus (T2DM), results in nontraumatic lower-limb amputations. When DPN is not detected early, disease progression is irreversible. Thus, biomarkers for diagnosing DPN are needed. We analyzed three data sets of T2DM DPN: two for mouse models (GSE70852 and GSE34889) and one for a human model (GSE24290). We found common differentially expressed genes (DEGs) in the two mouse data sets and validated them in the human data set. To identify the phenotypic function of the DEGs, we overexpressed them in zebrafish embryos. Clinical information and serum samples of T2DM patients with and without DPN were obtained from the Korea Biobank Network. To assess the plausibility of DEGs as biomarkers of DPN, we performed an enzyme-linked immunosorbent assay. Among the DEGs, only NPY and SLPI were validated in the human data set. As npy is conserved in zebrafish, its mRNA was injected into zebrafish embryos, and it was observed that the branches of the central nervous system became thicker and the number of dendritic branches increased. Baseline characteristics between T2DM patients with and without DPN did not differ, except for the sex ratio. The mean serum NPY level was higher in T2DM patients with DPN than in those without DPN (p = 0.0328), whereas serum SLPI levels did not differ (p = 0.9651). In the pathogenesis of DPN, NPY may play a protective role in the peripheral nervous system and may be useful as a biomarker for detecting T2DM DPN.


Masculinity lost: a systematic review of qualitative research on men with spinal cord injury.
Systematic, thematic, narrative review of qualitative literature. To systematically review qualitative research that explores the impact of spinal cord injury (SCI) on the gendered experience of men with SCI. A systematic search of databases and hand search of relevant journals to provide a thematic narrative review of articles, providing sufficient depth of information, relevant participant quotes and phenomenological insight into the gendered experience of men with SCI. Identified studies are summarised and common themes extracted and discussed in relation to relevant literature on masculinity, disability and health. Eight papers, representing four separate studies met the review criteria for relevance and rigour. Three broad, overlapping themes describing the gendered experience of men with SCI were identified: 'lost masculinity', outlining the impact of SCI on traditional masculine identity, 'fighting back', describing the battle to regain and reclaim masculinity and integrate disability into a revised identity and 'beyond hegemony', referring to possibilities beyond adherence to traditional masculine scripts. This review demonstrates a lack of explicit focus on men as gendered beings within the available qualitative literature. The findings are consistent with the limited quantitative data, which indicates that grappling with altered gendered identity is a central feature of life for men with SCI. Masculine identity emerges in this review as vulnerable to the impact of SCI, and given the strong links identified between masculinity, rehabilitation and health, as an aspect of experience that warrants more attention than it has received.


Lymphocyte to monocyte ratio and blood pressure variability in childhood hypertension-a pilot study.
The investigation of inflammatory background of hypertension (HTN) concentrates mainly on patients with primary HTN. The aim of the study was to analyze the role of new parameters of inflammation-lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR), in the population of children with primary (pHTN) and secondary renal hypertension (rHTN). The study group consisted of 70 children with pHTN, 46 patients with rHTN, and 30 age-matched normotensive controls. The retrospective analysis focused on the evaluation of LMR, NLR, and PLR values in relation to blood pressure (BP) parameters from in-office and ambulatory BP monitoring measurements. Twenty-four hours, daytime, and nighttime periods were evaluated. Blood pressure variability (BPV) was defined by standard deviation and coefficient of variation of analyzed values. LMR and NLR values in HTN patients differed significantly vs. controls. Dippers with pHTN demonstrated significant correlations between LMR, NLR, PLR, and markers of BPV, in 24 h and daytime diastolic BP and mean arterial pressure. In dippers with rHTN such correlations concerned only LMR. LMR may become a promising marker of BPV, useful in children with primary and secondary hypertension. Lymphocyte to monocyte ratio is a novel marker of blood pressure variability, connected to target-organ damage, in children with primary and secondary renal hypertension. Our study analyzes for the first time the connections between blood cell count-driven inflammatory markers (lymphocyte to monocyte, neutrophil to lymphocyte, and platelet to lymphocyte ratios) and parameters of blood pressure variability, and compares those ratios in children with primary and secondary hypertension. The increasing incidence of hypertension among children urges the search for simple methods of assessment of its complications. LMR may be of added value in the analysis of the inflammatory background of hypertension.


Refractive changes and visual quality in patients with corneal edema after cataract surgery.
To assess visual quality and stabilization of refractive changes in corneal edema patients after cataract surgery, using visual acuity (VA) and contrast sensitivity measurements. Sixty-one eyes were analysed, twenty-three with and thirty-eight without corneal edema. Uncorrected and corrected distance VA (UDVA and CDVA) were determined with an EDTRS chart, the contrast sensitivity function (CSF) under photopic and mesopic illumination conditions with a CVS-1000e chart, clinical refraction, and corneal topography. Measurements were taken preoperatively, 1-2 days, 1 and 3-months after surgery. Clinical refraction was converted to vector notation (M, J0, J45) and SPSS v26.0 was used for data analysis. An improvement of VA was observed through the postoperative period; changes between visits were significant for CDVA in both groups and for UDVA in the edema sample. Significant astigmatic changes (J0,J45) between visits were not observed, but M values showed a hyperopic tendency in the edema group and a myopic shift in the control group that did not change between visits, with statistically significant differences between groups. Controls had significantly better contrast sensitivity at high spatial frequencies. Under mesopic conditions, global contrast sensitivity losses were observed in the edema group, which improved between visits in the middle frequency range. Corneal edema patients had a significant reduction of CDVA, and frequency-selective sensitivity losses that evidence a visual quality loss. Clinical refraction may improve visual quality, but in edema patients these losses are related to corneal changes, which did not change at three months after surgery.


The effect of N-acetylcysteine in patients with non-cystic fibrosis bronchiectasis (NINCFB): study protocol for a multicentre, double-blind, randomised, placebo-controlled trial.
N-acetylcysteine (NAC), which is specifically involved in airway mucus clearance and antioxidation, is recommended by the treatment guideline for non-cystic fibrosis bronchiectasis (NCFB). However, there is little clinical evidence of its long-term efficacy concerning quality of life (QoL) and exacerbation in patients with NCFB. In addition, the influences of NAC on airway bacterial colonization, chronic inflammation and oxidative stress in NCFB are also unclear. NINCFB is a prospective, multicentre, double-blind, randomised, placebo-controlled trial that will recruit 119 patients with NCFB and randomly divide them into an NAC group (n = 79) and a control group (n = 40). Participants in the NAC group will receive 600 mg oral NAC twice daily for 52 weeks, while patients in the control group will receive 600 mg placebo twice daily for 52 weeks. The information at baseline will be collected once participants are enrolled. The primary endpoints are the changes in St George's Respiratory Questionnaire scores and the number of exacerbations in 52 weeks. The secondary endpoints are the 16S rRNA of sputum and the levels of inflammatory factors and oxidative stressors in sputum and serum. Other data related to radiography, lung function tests, number of oral and/or intravenous antibiotic therapies and adverse events (AEs) will also be analysed. Further subgroup analysis distinguished by the severity of disease, severity of lung function, airway bacterial colonization and exacerbation frequency will be performed. The objective of this study is to determine the long-term efficacy of NAC on QoL and exacerbation of NCFB and to explore the effectiveness of NAC for antibiosis, anti-inflammation and antioxidation in NCFB. The study results will provide high-quality clinical proof for the revision and optimization of treatment guidelines and for expert consensus on NCFB treatment. The trial was registered on the Chinese Clinical Trial Register at April 11, 2020 ( chictr.org.cn , ChiCTR2000031817).


Tertiary amines enhance reactions of organic contaminants with aqueous chlorine.
Through various anthropogenic inputs, tertiary amines can readily contaminate wastewater and drinking water sources and can form chlorammonium species (R(3)N(+)-Cl) during aqueous chlorine disinfection. This study investigated the less understood concept that these chlorammonium species can potentially enhance organic contaminant loss and increase disinfection byproduct formation to a greater extent than aqueous chlorine. Tertiary amines' effectiveness was highly dependent on amine structure as trimethylamine (TMA) and 4-morpholineethanesulfonic acid (MES) enhanced organic contaminant loss, while others (nitrilotriacetic acid (NTA) and creatinine (CRE)) were ineffective. MES addition up to 25 μM led to increased organic contaminant chlorination by up to three orders of magnitude while observing pseudo-first order kinetic behavior and a linear amine dose response. TMA addition up to 0.5 μM accelerated organic contaminant chlorination by almost two orders of magnitude, but occasionally deviated from pseudo-first order kinetics with incomplete organic contaminant degradation and a non-linear amine dose response - a result linked to TMA's rapid auto-decomposition over time. Byproduct formation was identical with and without amine addition, and thus the chlorination mechanisms are likely similar to aqueous chlorine. Results from this study improve the mechanistic understanding behind tertiary amine-enhanced chlorination.


Three CCAAT-boxes and a single cell cycle genes homology region (CHR) are the major regulating sites for transcription from the human cyclin B2 promoter.
Cyclins are essential regulators of the cell division cycle. Cyclin B associates with the cyclin-dependent kinase 1 (cdc2) to form a complex which is required for cells to undergo mitosis. In mammalian cells three B-type cyclins have been characterised, cyclin B1, B2 and B3. The cell cycle-dependent synthesis of cyclin B1 and B2 has been investigated in detail displaying maximum expression in G2 which is mainly regulated on the transcriptional level. We have previously shown that this regulation of the mouse cyclin B2 promoter is controlled by a cell cycle-dependent element (CDE) and the cell cycle genes homology region (CHR). Also in a number of other genes CDE/CHR elements repress transcription in G0 and G1 and lead to relief of repression later during the cell cycle. Here, we compare human and mouse cyclin B2 promoters. Both promoters share only nine regions with nucleotide identities. Three of these sites are CCAAT-boxes spaced 33 bp apart which can bind the NF-Y transcriptional activator. NF-Y binding to the human cyclin B2 promoter could be shown by chromatin immunoprecipitation (ChIP) assays. Activation by NF-Y is responsible for more than 93% of the total promoter activity as measured by cotransfecting a plasmid coding for a dominant-negative form of NF-YA. Cell cycle-dependent repression is regulated solely through a CHR. Surprisingly, in contrast to the mouse promoter the CHR in the human cyclin B2 promoter does not rely on a CDE site in tandem with it. Together with the recently described mouse cdc25C promoter, human cyclin B2 is the second identified gene which solely requires a CHR for its cell cycle regulation.


The Efficacy of Pericapsular Nerve Group Block Versus Facia Iliaca Block on Immediate Postoperative Pain and Opioid Consumption After Hip Arthroscopy Randomized Trial.
Postoperative pain after hip arthroscopy remains a major cause of patient dissatisfaction in the immediate postoperative period. Adequate postoperative analgesia is associated with increased patient satisfaction, earlier mobilization, and decreased opioid consumption. Therefore, there is a need for safe, reliable, and opioid- and motor-sparing methods of achieving postoperative analgesia following hip arthroscopy. We evaluated the efficacy of pericapsular nerve group (PENG) block vs fascia iliaca block (FIB) in reducing postoperative pain and analgesic consumption in the first 24 hours following hip arthroscopy. A prospective randomized double-blinded control clinical trial. At the arthroscopy unit of the orthopedic department of Assiut University Hospitals, Assiut, Egypt from 2019 to 2022. Forty-three patients comprising 18 women and 25 men scheduled for hip arthroscopy were randomized to receive a preoperative block with PENG or FIB from March 2019 to March 2022. The mean age was 27.9 years (standard deviation [SD], 6.2 years; range, 18-42 years) and the mean body mass index was 25.13 kg/m2 (SD, 5.08 kg/m2). Patients were randomized into 2 groups: group A comprising 20 patients that received FIB; and group B comprising 23 patients that received PENG block. The efficacies of FIB and PENG block were evaluated using Visual Analog Scale scores. Statistically significant differences in median pain scores and mean at rest pain scores were observed between the 2 groups at all measured time points following surgery (i.e., 6, 12, 18, and 24 hours). Further, dynamic pain scores (with hip flexion) scores significantly differed between the 2 groups at 24 hours postoperatively (P = 0.001). PENG block significantly decreased postoperative opioid use compared to FIB. Total opioid use in the 24-hour postoperative period was lower in the PENG group compared to the FIB group (16.5 ± 9.9 vs 27.5 ± 9.6; P < 005). Different hip pathologies and different interventions lead to different outcomes. Also, a larger sample size and longer follow-up duration are required. PENG block may represent the ideal regional anesthesia modality for hip arthroscopy as an alternative to more conventional regional nerve blocks, such as FIB, femoral nerve block, and lumbar plexus block. PENG block is reproducible, easily performed in the preoperative setting, and appears to spare motor function while providing prolonged sensory analgesia.


Etiological relationship between lipid metabolism and endometrial carcinoma.
Endometrial carcinoma (EC) has become one of the most common gynecological malignant neoplasms in developed countries worldwide. Studies have shown that this may be closely related to the abnormal metabolism of blood lipids, which was the most significant metabolic change in the human body in this cancer. In this review, we focus on the correlation between lipid metabolism and EC and discuss the evidence that abnormal lipid metabolism promotes an increase in EC growth and metabolism, as well as the regulatory mechanism and related signaling pathways involved in this relationship. In addition, we also discussed the research progress of targeted therapies and drug treatments for EC that act on lipid metabolism, and statins are expected to become adjuvant drugs for EC in the future. This review will provide a systematic view for a better understanding of the etiological relationship between lipid metabolism and EC and further open up new therapeutic possibilities and effective treatments for EC by targeting lipid metabolism.


Computational synthesis of cortical dendritic morphologies.
Neuronal morphologies provide the foundation for the electrical behavior of neurons, the connectomes they form, and the dynamical properties of the brain. Comprehensive neuron models are essential for defining cell types, discerning their functional roles, and investigating brain-disease-related dendritic alterations. However, a lack of understanding of the principles underlying neuron morphologies has hindered attempts to computationally synthesize morphologies for decades. We introduce a synthesis algorithm based on a topological descriptor of neurons, which enables the rapid digital reconstruction of entire brain regions from few reference cells. This topology-guided synthesis generates dendrites that are statistically similar to biological reconstructions in terms of morpho-electrical and connectivity properties and offers a significant opportunity to investigate the links between neuronal morphology and brain function across different spatiotemporal scales. Synthesized cortical networks based on structurally altered dendrites associated with diverse brain pathologies revealed principles linking branching properties to the structure of large-scale networks.


Glomus jugulare tumours in South Wales--a twenty-year review.
Fourteen patients with glomus jugulare tumours presenting over the last 20 years in South Wales are reviewed. All were treated with radiotherapy and only two died, both of whom had radiological evidence of extensive intrapetrosal spread. All the remainder had good relief of symptoms and are at present free from evidence of progressing tumour.


Author Correction: Exogenously applied growth regulators protect the cotton crop from heat-induced injury by modulating plant defense mechanism.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.


Anabolic phenotype in cartilage-specific mitogen-inducible gene-6 knockout mice is independent of transforming growth factor-α.
Osteoarthritis (OA) is a whole joint disorder with no disease modifying treatment currently available. The Epidermal Growth Factor Receptor (EGFR) signaling pathway plays an important role in cartilage/bone development and its ligand transforming growth factor-α (TGFα) is upregulated in OA. In contrast, Mitogen-inducible gene 6 (Mig6) is a negative regulator of EGFR, and cartilage-specific Mig-6 deletion results in anabolic effects on cartilage and formation of chondro-osseus nodules (CON). We aimed to attenuate EGFR signaling by inhibiting TGFα production in cartilage-specific Mig6 deficient mice, to test whether this would prevent the formation of CONs. We generated double knockout mice by crossing cartilage-specific Mig-6fl/flCol2a1-Cre+/- and whole-body Tgfa± mice to generate experimental and control wild-type mice. Knee and elbow sections were used to examine articular cartilage thickness, cell density, and osteoclast presence. Additionally, immunohistochemistry was completed to analyze phospho-EGFR and SOX9. Mig-6 deficient mice display cartilage thickening and CONs at 12 weeks in both the elbow and knee joints, which is independent of TGFα ligand presence. Similarly, articular cartilage cell density is increased in Mig6-cKO/Tgfa-KO and Mig6-cKOmice, but not Tgfa-KO mice, and displays increased SOX9 and phospho-EGFR staining. The articular cartilage displays increased thickness/cell density and CON formation independent of the presence of TGFα, suggesting the anabolic phenotype in the Mig6-deficient mice is independent of TGFα/EGFR binding. The anabolic phenotype may be due to an alternative EGFR ligand activation, or other non-EGFR specific mechanism. More research is required to elucidate the exact pathway responsible for the anabolic effects.


Behavioral effects of aminoadamantane class NMDA receptor antagonists on schedule-induced alcohol and self-administration of water in mice.
Aminoadamantanes represent a class of NMDA glutamate receptor antagonists that reduce alcohol consumption and may prevent alcohol-induced neuronal adaptations and side effects. Behavioral specificity of memantine and amantadine on alcohol drinking in a schedule-induced polydipsia (SIP) task was investigated in mice. Male C57BL/6J mice were food-deprived and divided into four groups: 5% alcohol SIP, water SIP, 1 h limited access regulatory water drinking, and a control group to determine if either drug altered ethanol drinking. Behavioral specificity of memantine (5, 10, and 25 mg/kg, ip) and amantadine (20, 40, and 60 mg/kg, ip) was determined by comparing alterations in alcohol or water consumption in SIP and regulatory water drinking. Drug effects on SIP drinking-specific measures (grams per kilogram consumption) were also compared to nondrinking measures (locomotion, head-entries for food, and lick efficiency). Compared to saline, memantine reduced alcohol SIP drinking (10 and 25 mg/kg). Memantine increased locomotion during alcohol SIP (25 mg/kg) and during water SIP (5 and 25 mg/kg). In contrast, amantadine reduced both alcohol SIP (40 mg/kg) and water SIP (40 and 60 mg/kg). Both drugs reduced regulatory water consumption over the entire dose range tested. Blood alcohol concentrations indicated consumption of physiologically meaningful amounts of alcohol during SIP, and that changes in alcohol metabolism did not account for drug-induced reductions in alcohol drinking. In addition to reducing alcohol drinking, both drugs had other behavioral effects that included reductions in regulatory drinking. These results suggest that the therapeutic utility of these drugs for ameliorating human alcohol addiction remains questionable.


The emergence of the cortical GABAergic neuron: with particular reference to some peptidergic subpopulations.
The technical developments which have led to our present ability to make predictions about neurochemical identity from morphological observations are retraced with particular reference to the GABAergic neuron and its many subdivisions. The synaptology of four peptidergic sub-populations in the cerebral cortex is examined and described in detail. It is concluded that the recognition of Gray Type 1 and Type 2 synapse types continues to provide a key element in our analysis and understanding of the connectivity of the CNS.


Timing and volume of information produced for the Otolaryngologist during the COVID-19 pandemic in the UK: A review of the volume of online literature.
The SARS-CoV-2 was first reported in December 2019 in Wuhan, China and has been declared a pandemic in March 2020. COVID-19 has caused unprecedented and lasting biopsychosocial effects worldwide. All healthcare professionals have faced life-threatening risks by attending their daily jobs. The daily emergence of advice and guidelines was necessary to ensure the safety of patients and staff. To this effect, all elective services came to a halt to preserve hospitals' capacity for dealing with the sickest. This retrospective, descriptive review aims to assess the volume and timing of the advice released specifically relevant to UK ENT specialists. Two separate searches were performed. One involved online advice published in English by international, national and ENT-specific organisations between January 1 and May 31. The date, title, source, type of advice and link to the advice were recorded in Excel. The resources were analysed per week of publication. A second separate search for peer-reviewed publications was conducted using PubMed Central and Cochrane databases. COVID-19-related guidance was considered, of which 175 were identified. 52/175 (29.7%) articles were published by international organisations. 56/175 (32%) were produced by national organisations, and 67/175 (38.28%) were produced by ENT specific organisations. The peak guidance production took place in the third and fourth week of March (16/03/2020-29/03/2020) with 72/175 publications. Of these, 27/70 came from the international category, 17/70 from national bodies and 26/70 from ENT-specific organisations. 13 863 total publications relating to COVID-19 were found using PubMed and Cochrane search strategies; 76% were relevant to ENT. The challenges faced by ENT relate to the unprecedented, sudden and daily changes to clinical practice. Multiple bodies interpreted the guidance, giving an opportunity for confusion and delay in treatments for patients. Implementing a system with clear lines of communication and dissemination of information will improve our response to future pandemic events whilst maintaining a commercial awareness to better use the human and financial resources of an already financially restricted NHS.


Is China approaching the inflection point of the ecological Kuznets curve? Analysis based on ecosystem service value at the county level.
Accounting for the ecosystem service values (ESVs) and discussing the relationship between the ESVs and economic development can help achieve sustainable ecological development. Therefore, this paper evaluates the county-level ESVs of various land types in China, and depicts the distribution of ESVs in various urban agglomerations. In addition, the nonlinear relationship between ESVs and economic development is revealed. The main findings are as follows: (1) From 2000 to 2018, the ESVs in China decreased, and the decline rate of ESVs in urban agglomerations is much higher than that of China as a whole. (2) The decline rate of ESVs in core cities is much higher than in urban agglomerations, and the decline rate of ESVs is higher in areas close to core cities and lower in areas far from core cities. (3) The ecological Kuznets curve of China has a positive "U" shape, and the ecological Kuznets curve of urban agglomerations has an "N" shape; the ecological Kuznets curve of core cities has a positive "U" shape, while the ESVs of other cities decreases monotonically with the increase of the economic level.


A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C.
The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, in part through inhibition of heat shock proteins. If quercetin demonstrates safety and antiviral activity in patients, then it could be developed into an inexpensive HCV treatment for third world countries or other affected populations that lack financial means to cover the cost of mainstream antivirals. A phase 1 dose escalation study was performed to evaluate the safety of quercetin in 30 untreated patients with chronic HCV infection and to preliminarily characterize quercetin's potential in suppressing viral load and/or liver injury. Quercetin displayed safety in all trial participants. Additionally, 8 patients showed a "clinically meaningful" 0.41-log viral load decrease. There was a positive correlation (r = 0.41, p = 0.03) indicating a tendency for HCV decrease in patients with a lower ratio of plasma quercetin relative to dose. No significant changes in aspartate transaminase and alanine transaminase were detected. In conclusion, quercetin exhibited safety (up to 5 g daily) and there was a potential for antiviral activity in some hepatitis C patients.


Hodgkin's disease in a killer whale (Orcinus orca).
Hodgkin's disease (HD) is reported in a killer whale (Orcinus orca). Generalized lymphadenopathy and splenomegaly were noted at necropsy and histopathological examination revealed diffuse proliferation of atypical large cells with huge eosinophilic nucleoli. They were often multinucleated, and binucleated forms characteristic of Sternberg-Reed cells of human HD were occasionally present. There was no cytological atypia in the background lymphocytes. Thus, the lesion was identified as analogous to HD in man. To our knowledge, this is the first recorded case of HD in the killer whale.


Fatty acid-membrane interactions in isolated cardiac mitochondria and erythrocytes.
The effects of long-chain fatty acids on mitochondrial functions and red cell stability were studied. In albumin-containing incubation media, fatty acid distribution between the albumin-bound and the unbound fraction was estimated by calculation. When fatty acids are compared to one another on the basis of identical unbound concentrations, their effectiveness differs by orders of magnitude. Fatty acids stimulate mitochondrial basic oxygen consumption, thus lowering the respiratory control index, without changing the ATP/O ratio at lower concentrations. Lower concentrations increase Ca2+ uptake velocity, but decrease maximal Ca2+ storage capacity. The order of effectiveness of different fatty acids is the same for both oxidative phosphorylation and Ca2+ uptake. The influence of fatty acids on red cell stability in hypotonic media is similar to these effects both in concentration range and in order of effectiveness. The influence of fatty acids on red cell stability and their critical micellar concentrations were investigated because these are general characteristics of 'detergent-like' compounds. Critical micellar concentrations of the fatty acids in physiological salt buffers are, in general, at least 10-fold higher than the concentrations exhibiting membrane effects in vitro. Based on these findings it is suggested that, of the various concentrations reported in literature for myocardial non-esterified fatty acids, only the lowest values are physiologically possible.


Realizing the Potential of Gene Therapies for Rare and Ultra-Rare Inherited Diseases.
Rare and ultrarare diseases have been central to the field of gene therapy since its earliest stage, and we are now witnessing more and more effective treatments entering the clinical realm for patients in need. However, despite promising results across a range of rare diseases, transformative gene therapies may not be available and accessible to patients for nonmedical reasons. Traditional regulatory and commercialization pathways to licensed products seem to be prohibitive for ultrasmall patient populations. Here, we highlight some of the challenges of delivering gene therapies in rare diseases and discuss innovative solutions being proposed by the gene therapy community.


Obese children show increased intimal wall thickness and decreased pulse wave velocity.
Childhood obesity confers an increased risk of vascular changes and adult cardiovascular disease. Using a high-resolution ultrasound technique that enables separation of intimal and medial layers, we examined the intimal thickness (IT) and intimal-medial thickness (IMT) of radial (RA) and dorsal pedal (DPA) arteries and the pulse wave velocity (PWV) in overweight/obese children and adolescents and in healthy subjects. IT and IMT of RA and DPA and PWV were measured in 33 obese children and adolescents (13.9+/-1.6 years) and in 18 matched lean controls (14.3+/-2.2). Increased RA IT was found in the obese group, whereas no differences in RA IMT or medial thickness were observed. Obese females accounted for the entire difference in RA IT (P=0.04). DPA IT was inversely correlated with HDL cholesterol in the obese group (-0.56, P=0.0089). PWV was lower in the obese group than in the lean group (6.2+/-0.8 versus 7.0+/-0.9 m s(-1), respectively; P=0.001). Obese children and adolescents, primarily females, present with increased RA IT. The decreased PWV in the obese versus lean subjects might reflect general vasodilatation.


Changes in the prevalence of HBV infection in pregnant women in Turkey between 1995 and 2015: a 20-year evaluation.
To determine changes in hepatitis B virus (HBV) prevalence across three different time periods in pregnant women. This was a retrospective study of pregnant women attending four healthcare centres between January 1995 and May 2015. Data for serum hepatitis B surface antigen (HBsAg) and anti-HBs levels were collected from routine antenatal screening records. The 20-year study was divided into three periods: 1995-2001, 2002-2008 and 2009-2015. The results are presented by the women's age and gravidity as possible determinants of HBV infection. 7605 pregnant women (56.0% primigravidae) (mean age 23.4±4.8 years) were tested for markers of HBV infection. 3010 pregnant women were screened between 1995 and 2001, 2995 between 2002 and 2008, and 1600 between 2009 and 2015. The overall prevalence of HBsAg and anti-HBs positivity in the 7605 pregnant women was 1.5% (n=114) and 11.5% (n=877), respectively. Regarding temporal change in the prevalence of HBV markers, HBsAg decreased significantly from 2.6% to 0.8% (p<0.01), while anti-HBs increased significantly from 9.5% to 17.5% (p<0.01), between the first and last study periods. Multigravidae and older women had higher HBsAg and anti-HBs positivity compared to primigravidae. The data suggest that the prevalence of HBsAg positivity is gradually decreasing among pregnant women, while the level of HBsAg antibody seropositivity is lower than expected. HBV carrier rate increases with increasing age and gravidity. In addition to the national HBV immunisation programme, the prevention of perinatal transmission should also be prioritised to decrease the HBV pool of infection.


Chronic dietary exposure to arsenic at environmentally relevant concentrations impairs cognitive performance in adult zebrafish (Danio rerio) via oxidative stress and dopaminergic dysfunction.
The current study was designed to evaluate the effects of chronic dietary arsenic exposure on the cognitive performance of adult zebrafish and uncover probable pathways by which arsenic mediates such neurotoxic effects. Adult zebrafish were treated with 3 different dietary arsenic concentrations (30, 60, and 100 μg/g dry weight (dw), as arsenite) in addition to control for 60 days. A latent learning paradigm, which employs a complex maze, was used to assess the cognitive performance of fish. Our results demonstrated that dietary treatment with arsenic, especially at medium (60 μg/g dw) and high (100 μg/g dw) exposure dose levels, significantly impaired the performance of fish in various latent learning tasks evaluated in the present study. Concomitant with cognitive dysfunction, chronic dietary exposure to arsenic was also found to increase arsenic accumulation and dopamine levels, and induce oxidative stress (reduced thiol redox, increased lipid peroxidation and expression of antioxidant enzyme genes) in the brain of zebrafish in a dose-dependent manner. Dopaminergic system in the brain is known to play a critical role in regulating cognitive behaviours in fish, and our observations suggested that chronic dietary treatment with medium and high arsenic doses leads to significant alterations in the expression of genes involved in dopamine signaling (dopamine receptors), synthesis (thyroxine hydroxylase) and metabolism (monoamine oxidase) in the zebrafish brain. Moreover, we also recorded significant downregulation of genes such as the brain-derived neurotrophic factor (BDNF) and ectonucleotidases (entpd2_mg, entpd2_mq, and 5'-nucleotidase), which are critical for learning and memory functions, in the zebrafish brain following chronic dietary exposure to arsenic. Overall, the present study suggests that chronic environmentally relevant dietary exposure to arsenic can impair the cognitive performance in zebrafish, essentially by inducing oxidative stress and disrupting the dopaminergic neurotransmission in the brain.


Effect of 'Perceived control' in management of anxious patients undergoing endodontic therapy by use of an electronic communication system.
From time immemorial, fear and anxiety have been associated with dental treatment. Coping with this fear and anxiety has been one of the most vexing problems with which the individual dentist, as well as the profession has had to contend. Hence this study was undertaken to evaluate a new technique for management of such anxious patients. The aim of this study is to evaluate the efficacy of using 'Perceived control' for the management of anxious patients undergoing endodontic therapy. 'A communication device designed by the author and named as "Touch N' Tell" (Patent no: 234291, Government of India) was installed on the dental chair which helps to create an effective communiqué between the patient and dentist during the dental procedure. Sixty anxious patients were selected using Modified Dental Anxiety Scale (MDAS), and were divided into two groups. For group A, the patients were treated along with the use of 'communication system' installed on the dental chair, whereas the patients were managed in a routine manner for Group B. The post operative MDAS scores were recorded for both the groups. The mean change in anxiety levels was calculated for both the groups. Statistical analysis was done using unpaired t-test. A significant decrease in the mean anxiety levels was observed in the group where 'communication system' was used as a measure of perceived control.


Free radicals mediate systemic acquired resistance.
Systemic acquired resistance (SAR) is a form of resistance that protects plants against a broad spectrum of secondary infections. However, exploiting SAR for the protection of agriculturally important plants warrants a thorough investigation of the mutual interrelationships among the various signals that mediate SAR. Here, we show that nitric oxide (NO) and reactive oxygen species (ROS) serve as inducers of SAR in a concentration-dependent manner. Thus, genetic mutations that either inhibit NO/ROS production or increase NO accumulation (e.g., a mutation in S-nitrosoglutathione reductase [GSNOR]) abrogate SAR. Different ROS function additively to generate the fatty-acid-derived azelaic acid (AzA), which in turn induces production of the SAR inducer glycerol-3-phosphate (G3P). Notably, this NO/ROS→AzA→G3P-induced signaling functions in parallel with salicylic acid-derived signaling. We propose that the parallel operation of NO/ROS and SA pathways facilitates coordinated regulation in order to ensure optimal induction of SAR.


Cytotoxicity of municipal solid waste incinerator ash wastes toward mammalian kidney cell lines.
In this study, three municipal solid waste incinerator (MSWI) ash wastes-bottom ash, scrubber residue, and baghouse ash-were extracted using a toxicity characteristic leaching procedure (TCLP) extractant. These so-called final TCLP extracts were applied to African green monkey kidney cells (Vero), baby hamster kidney cells (BHK-21), and pig kidney cells (PK-15), multi-well absorption reader analysis was performed to test how the cytotoxicity of the incineration ashes would affect the digestive systems of animals. Ion-coupled plasma analyses indicated that the baghouse ash extract possessed the highest pH and heavy metal concentration, its cytotoxicity was also the highest. In contrast, the bottom ash and the scrubber residue exhibited very low cytotoxicities. The cytotoxicities of mixtures of baghouse ash and scrubber residue toward the three tested cell lines increased as the relative ratio of the baghouse ash increased, especially for the Vero cells. The slight cytotoxicity of the scrubber residue arose mainly from the presence of Cr species, whereas the high cytotoxicity of the baghouse ash resulted from its high content of heavy metals and alkali ions. In addition, it appears that the dissolved total organic carbon content of these ash wastes can reduce the cytotoxicity of ash wastes that collect in animal cells.


Advance in chitosan hydrolysis by non-specific cellulases.
Besides the specific chitinase, chitosanase and lysozyme, chitosan also could be hydrolyzed by some non-specific enzymes such as cellulase, protease, lipase and pepsin, especially cellulase, which show high activity on chitosan. Almost all the cellulases produced by different kinds of microorganisms could degrade chitosan to chitooligomers. The existence of bifunctional enzymes with cellulase and chitosanase activity is one of the reasons for cellulase on chitosan hydrolysis. The bifunctional cellulase-chitosanases mainly belong to glycoside hydrolase family 8 (GH-8), few belong to GH-5 and GH-7, according to the homogeneity analysis of amino acids sequences. Their three dimensional structures however have not been clearly determined. This paper may serve as a guide for a further study on the relationship between structure and function of chitosanolytic cellulases.


A survey on the use of mice, pigs, dogs and monkeys as animal models in biomedical research in Spain.
The use of animals in biomedical science remains controversial. An individual's level of concern is generally influenced by their culture, previous or current experience with animals, and the specific animal species in question. In this study we aimed to explore what people in Spain who had never or who no longer worked with laboratory animals thought of the use of mice, pigs, dogs and monkeys for biomedical research purposes. We also aimed to determine whether or not people currently involved in biomedical research with the aforementioned species felt their work was justified. The study comprised a total of 807 participants (never worked = 285, used to work = 56, currently working = 466), almost two thirds of whom were women. Our results revealed that the phylogenetic scale is an important factor in people's opinions of the use of certain species in research. The percentage of people who were against the use of dogs or monkeys was higher than that of those who were against the use of mice or pigs. The main reasons given for having stopped working with laboratory animals were change of professional career and change in research project. Participants who were currently working with animals believed that their work was justified, but said they did not talk about it with people outside their immediate social circle. Our findings suggest that there is a difference in moral status between monkeys and mice, as well as between companion animals (dogs) and farm animals (pigs). Our results support the idea that working with laboratory animals is a sensitive issue in Spain.


[Evaluation by quality of life questionnaires in patients undergoing strabismus surgery in Graves' disease].
To evaluate the improvement in quality of life of patients operated within 6 months for strabismus in Graves' disease using a questionnaire. A retrospective study was based on a cohort of patients undergoing strabismus surgery for Graves' disease at the Nancy university medical center between June 2015 and January 2017. A quality-of-life questionnaire composed of the functional GO QOL questionnaire plus 10 additional questions was given to patients. The questionnaires were completed by patients in consultation before surgery and then at six months postoperatively. A subgroup analysis was conducted to identify potential risk factors such as smoking, orbital decompression, duration of disease progression, number of surgeries, previous treatments or gender influences on the progression of the postoperative score. Thirty-three patients (15 men/18 women) underwent surgery, with mean age 56 years; 16 (48 %) were smokers, 24 (70 %) were operated for the first time for strabismus. 8 patients (24 %) had a history of surgical orbital decompression. The mean preoperative GO QOLf was 30 (±23.8), which increased to 72 (±29.6) postoperatively (P=0.004). All the answers to the questions proposed were improved by surgery. The most improved items were difficulty in extreme gaze+6.82 points (P=0.001) and going down stairs +6.81 (P=0.002). Smokers had a lower preoperative GO QOLf than non-smokers (25±22.84 vs. 34±24.55); the same was true for their postoperative improvement (35±34.5 points vs. 50±18.8, P=0.002). History of orbital decompression did not appear to influence quality of life (21±25.39 vs. 65±33.98); the same was true for previous corticosteroid or immunosuppressant treatment (28±23.52 vs. 67±28.24), respectively P=0.42; P=0.73. Gender did not appear to influence the results P=0.17. First-time strabismus surgery patients showed a tendency which was not significant toward better improvement after 2 or 3 surgeries (respectively 45 vs. 39 vs. 33) P=0.056. There was no correlation between the duration of the disease and the change in the GO QOLf (R=0.04). This study confirms that strabismus surgery significantly improves the quality of life of patients with Graves' ophthalmopathy. The GO QOLf demonstrates its effectiveness in highlighting this progression. Our ten additional questions proved to be very good tools for assessing this condition.


Persistent nasal methicillin-resistant staphylococcus aureus carriage in hemodialysis outpatients: a predictor of worse outcome.
Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a well defined risk factor for subsequent bacteremia and death in various groups of patients, but its impact on outcome in patients receiving long-term hemodialysis (HD) is under debate. This prospective interventional cohort study (performed 2004 to 2010) enrolled 289 HD outpatients of an urban dialysis-unit. Nasal swab cultures for MRSA were performed in all patients upon first admission, at transfer from another dialysis facility or readmission after hospitalisation. Nasal MRSA carriers were treated in a separate ward and received mupirocin nasal ointment. Concomitant extra-nasal MRSA colonization was treated with 0.2% chlorhexidine mouth rinse (throat) or octenidine dihydrochloride containing antiseptic soaps and 2% chlorhexidine body washes (skin). Clinical data and outcome of carriers and noncarriers were systematically analyzed. The screening approach identified 34 nasal MRSA carriers (11.7%). Extra-nasal MRSA colonization was observed in 11/34 (32%) nasal MRSA carriers. History of malignancy and an increased Charlson Comorbidity Index were significant predictors for nasal MRSA carriers, whereas traditional risk factors for MRSA colonization or markers of inflammation or malnutrition were not able to discriminate. Kaplan-Meier analysis demonstrated significant survival differences between MRSA carriers and noncarriers. Mupirocin ointment persistently eliminated nasal MRSA colonization in 26/34 (73.5%) patients. Persistent nasal MRSA carriers with failure of this eradication approach had an extremely poor prognosis with an all-cause mortality rate >85%. Nasal MRSA carriage with failure of mupirocin decolonization was associated with increased mortality despite a lack of overt clinical signs of infection. Further studies are needed to demonstrate whether nasal MRSA colonization represents a novel predictor of worse outcome or just another surrogate marker of the burden of comorbid diseases leading to fatal outcome in HD patients.


Serum concentration of calcium, 1,25 vitamin D and parathyroid hormone are not correlated with coronary calcifications. An electron beam computed tomography study.
The amount of coronary artery calcification, measured using electron beam computed tomography, is correlated with the volume of coronary artery atherosclerotic plaque, the severity of stenosis by angiography, and with the likelihood of future cardiovascular events. The deposition of calcium in atherosclerotic plaques may also be influenced by determinants of calcium metabolism, thus contributing to the variance of the relation between coronary artery calcification and extent of atherosclerosis. Our objective was to determine whether this variance could be explained by differences in the parameters of calcium metabolism. We measured serum concentrations of calcium, 1,25(OH)2 vitamin D and parathyroid hormone (PTH) in 50 subjects undergoing angiography for clinical indications, and evaluated the correlations between these concentrations and calcium deposition in the coronary arteries, and the ratio of calcium deposition to extent of atherosclerosis using coronary angiography. Serum concentrations of calcium 1,25(OH)2 vitamin D and PTH were not correlated with coronary calcification or the ratio of coronary calcification to the extent of coronary stenosis. We conclude that, in subjects undergoing coronary angiography, the variance of the relationship between coronary atherosclerosis and coronary calcium is not a result of differences in serum concentrations of calcium, 1,25(OH)2 vitamin D or PTH.


Efficacy of endodontic applications of ozone and low-temperature atmospheric pressure plasma on root canals infected with Enterococcus faecalis.
This study aimed to compare the antimicrobial efficacy of low-temperature atmospheric pressure plasma (LTAPP) design and gaseous ozone delivery system with 2.5% NaOCl on Enterococcus faecalis in root canal walls and dentine tubules. The samples were divided into LTAPP (n = 12), ozone (n = 12), NaOCl (positive control, n = 12) and saline (negative control, n = 6) groups. Microbial samples were collected using paper points and dentin chips from root canals. Antimicrobial efficacy was assessed by counting the colony-forming units of Ent. faecalis before and after each irrigation protocol. Data were analysed using Kruskal-Wallis, Wilcoxon signed-rank, Friedman and Bonferroni t (Dunn's test)-tests (P = 0.05). The microbial sampling with paper points showed antibacterial efficacy of NaOCl, LTAPP, ozone and saline in descending order, respectively (P < 0.05). The microbial sampling with dentin chips demonstrated a superior efficacy of LTAPP compared with NaOCl in the middle third (P < 0.05), while both had similar effects in coronal and apical thirds (P > 0.05). NaOCl and LTAPP were better than ozone at the coronal and middle parts of the root canals (P < 0.05). These findings led us to suggest that LTAPP, which has no thermal and chemical effects, may be of great aid in endodontic treatment. The present study handles different perspectives on chemomechanical preparation of root canals. Ozone and low-temperature atmospheric pressure plasma (LTAPP) were investigated to determine whether they could be an alternative for NaOCl. Up to now, chemical solutions (NaOCl, chlorhexidine digluconate, etc...) have been used to disinfect the root canals. When the reported effects of LTAPP on biological and chemical decontamination were taken into consideration, a question rose whether it has antimicrobial efficacy in root canals infected with E. faecalis. According to the findings of the present study, LTAPP may constitute a promising aid in endodontics in disinfection of root canals.


Time to relapse in chronic lymphocytic leukemia and DNA-methylation-based biological age.
Chronic lymphocytic leukemia (CLL) is a mature B cell neoplasm with a predilection for older individuals. While previous studies have identified epigenetic signatures associated with CLL, whether age-related DNA methylation changes modulate CLL relapse remains elusive. In this study, we examined the association between epigenetic age acceleration and time to CLL relapse in a publicly available dataset. DNA methylation profiling of 35 CLL patients prior to initiating chemoimmunotherapy was performed using the Infinium HumanMethylation450 BeadChip. Four epigenetic age acceleration metrics (intrinsic epigenetic age acceleration [IEAA], extrinsic epigenetic age acceleration [EEAA], PhenoAge acceleration [PhenoAA], and GrimAge acceleration [GrimAA]) were estimated from blood DNA methylation levels. Linear, quantile, and logistic regression and receiver operating characteristic curve analyses were conducted to assess the association between each epigenetic age metric and time to CLL relapse. EEAA (p = 0.011) and PhenoAA (p = 0.046) were negatively and GrimAA (p = 0.040) was positively associated with time to CLL relapse. Simultaneous assessment of EEAA and GrimAA in male patients distinguished patients who relapsed early from patients who relapsed later (p = 0.039). No associations were observed with IEAA. These findings suggest epigenetic age acceleration prior to chemoimmunotherapy initiation is associated with time to CLL relapse. Our results provide novel insight into the association between age-related DNA methylation changes and CLL relapse and may serve has biomarkers for treatment relapse, and potentially, treatment selection.


Conceptualizing syntactic categories as semantic categories: Unifying part-of-speech identification and semantics using co-occurrence vector averaging.
Co-occurrence models have been of considerable interest to psychologists because they are built on very simple functionality. This is particularly clear in the case of prediction models, such as the continuous skip-gram model introduced in Mikolov, Chen, Corrado, and Dean (2013), because these models depend on functionality closely related to the simple Rescorla-Wagner model of discriminant learning in nonhuman animals (Rescorla & Wagner, 1972), which has a rich history within psychology as a model of many animal learning processes. We replicate and extend earlier work showing that it is possible to extract accurate information about syntactic category and morphological family membership directly from patterns of word co-occurrence, and provide evidence from four experiments showing that this information predicts human reaction times and accuracy for class membership decisions.


Preoperative vascular evaluation in living donor liver transplantation for biliary atresia.
Liver transplantation is an important treatment option in the management of end-stage liver disease. Preoperative vascular evaluation plays an important role for a safe and successful operation, especially in pediatric patients undergoing living donor liver transplantation (LDLT). The purpose of this study is to assess the usefulness and accuracy of Doppler ultrasound (US), computed tomographic angiography (CTA), and magnetic resonance angiography (MRA) in evaluating vascular anomalies in patients with biliary atresia (BA) undergoing LDLT. Images of Doppler US, CTA, and MRA for preoperative vascular evaluation in 55 patients with BA undergoing LDLT were reviewed with the operative findings. All patients underwent preoperative US, CTA, and MRA. Pathologic portal vein (n = 18), interruption of the retrohepatic vena cava (n = 1), and aberrant right hepatic artery from the superior mesenteric artery (n = 2) were confirmed during the transplantation. The success rates of CTA and MRA in identifying vascular anomalies were 96% and 82%, respectively (P = .01). The sensitivity, specificity, and accuracy of Doppler US were 89%, 94%, and 92%, respectively. For CTA, it was 94%, 97%, and 96%, respectively; for MRA (including technical failure), it was 75%, 97%, and 89%, respectively. Doppler US serves as an initial assessment for vascular evaluation and has the advantage in determining vascular flow quantities. CTA and MRA are used for precise surgical planning. However, MRA has lower success and accuracy rates when compared with CTA (P = .01). Doppler US with CTA can provide accurate preoperative vascular imaging in patients with BA undergoing LDLT.


Metallogels through glyme coordination.
Glyme intercalation in copper-thiolate polymers is studied. The amorphous polymer network observed is significantly stronger than previously reported coinage metal-thiolate supramolecular hydrogels synthesized without glyme. Glyme chain length and water content strongly influence mechanical and optical behavior.


Fused whole-heart coronary and myocardial scar imaging using 3-T CMR. Implications for planning of cardiac resynchronization therapy and coronary revascularization.
The aim of this study was to demonstrate the feasibility of providing spatially matched, 3-dimensional (3D) myocardial scar and coronary imaging for the purpose of fused volumetric image display in patients undergoing cardiac resynchronization therapy (CRT) or coronary artery revascularization (CAR). Clinical success in coronary vascular-based interventions is mitigated by the presence of scar in related myocardium. Pre-procedural fused volumetric imaging of both myocardial scar and coronary vasculature may benefit pre-procedural planning and patient selection in populations referred for CRT or CAR. A total of 55 studies were performed in patients referred for either CRT (n = 42) or CAR (n = 13). Coronary-enhanced and scar-enhanced imaging was performed on a 3-T cardiac magnetic resonance scanner using the same cardiac-gated, 3D, free-breathing cardiac magnetic resonance technique during and 20 minutes following slow gadolinium infusion. Matched image datasets were fused and volume-rendered to simultaneously display coronary anatomy and myocardial scar. Visual scoring of coronary artery, coronary vein, and myocardial scar image quality (score 0 to 4) was performed. The clinical impact of imaging was also scored using a physician survey. Mean age was 57 ± 14 years. Combined 3D coronary and scar imaging was successful in 49 studies (89%). A quality score ≥ 2 was obtained for 97% of proximal- and mid-coronary artery and vein segments. The mean quality score of 3D scar imaging was 2.8 ± 1.0 and was scored as ≥ 2 in 86% of patients with myocardial scar. All patients with a scar quality score ≥ 2 achieved successful image fusion. Transmural scar was present below ≥ 1 planned target vessel in 9 patients (39%) planned for CRT and 8 patients (62%) planned for CAR. Physician surveys demonstrated incremental clinical impact in 67% of patients. Three-dimensional myocardial scar and coronary imaging with fused volumetric display is clinically feasible and may be valuable for the planning of vascular-based interventions when regional myocardial scar is pertinent to therapeutic success.


Endovascular Management of Renal Arteriovenous Fistula With Large Aneurysm Masquerading as a Renal Cyst.
Large renal aneurysms can masquerade as simple renal cysts on ultrasound, especially if Doppler examination is not routinely done to assess flow characteristics. We present a case report of a 26-year-old male, as a clinical challenge in urology, who had minimal symptoms, yet had an arteriovenous fistula with a large aneurysm which was diagnosed as a parapelvic cyst on ultrasound. Endovascular treatment of the arteriovenous fistula was done using a vascular plug with satisfactory outcomes.


Positive clinical experience with misonidazole in brachytherapy and external radiotherapy.
We performed a clinical evaluation of Misonidazole (MISO) radiosensitization in brachytherapy and two schedules of hypofractionated external radiotherapy in 3 non randomized studies. MISO (1 g/m2/d) was administered to patients with ENT tumors treated by brachytherapy, two applications of 35 Gy each with an interval of 1 month. For 46 patients with tumor responses less than 50% (in the largest dimension) at time of second application, 21 received MISO and 25 did not. For these poorly radiosensitive tumors, the addition of MISO significantly increased the rate of complete remission from 9/25 (36%) in controls to 14/21 (67%) (p less than 0.05). We studied MISO with radiation hypofractionation for conservative breast cancer with 4 fractions over 17 days (5 Gy on days 1, 3 and 6.5 Gy on days 15 and 17). Brachytherapy alone was delivered three weeks later. MISO (1 g/m2/d) was given to 38 patients with 87 acting as controls. Radiosensitization was measured by mean tumor diameter at brachytherapy, which showed a residual mass of 33% in the group without MISO and only 17% in the group with MISO (p less than 0.05). We also studied MISO with radiation hypofractionation for large ENT tumors with 14 fractions over 45 days, 2 sessions with a 4 hour interval per day for totals of 6 Gy on days 1 and 3; 8 Gy on days 15, 17, 29, 31; and 6 Gy on day 45. MISO (1 g/m2/d) was given to 49 patients with 21 acting as controls. MISO increased the rate of complete remission from 7/21 (33%) in controls to 32/49 (65%) (p less than 0.02).


Levels and human health risk assessments of heavy metals in fish tissue obtained from the agricultural heritage rice-fish-farming system in China.
China began to practice Rice-fish-farming system (RFFS) 1700 years ago. Nowadays, the widely spread of metals could be potential threats to the quality of RFFS fish. In this study, Pb, Cd, Hg, As and Cr as the top five most toxic heavy metals were determined in six species of RFFS fish meat obtained from 7 provinces in south China. The mean concentrations of metals in RFFS fish followed Pb (36.89 μg/kg) > As (33.36 μg/kg) > Cr (18.54 μg/kg) > Hg (16.35 μg/kg) > Cd (2.01 μg/kg), which were mostly lower in comparison with fish from traditional aquaculture systems raised by fish feeds. Grass carp obtained lower metal concentrations compared with other fishes, possibly indicating the importance of feeding habits of RFFS fish. Concentrations of metals in fish and RFFS sediment were in good correlations, and benthic fish obtained high pollution levels, suggesting the accumulation of metals through the direct contact with sediment. Risks assessments coupled with Monte Carlo simulation indicated the potential non-carcinogenic risks and carcinogenic risks decreased following As > Hg > Cr ≈ Pb > Cd, and As > Cr > Cd > Pb, respectively. These results suggested RFFS is still a successful mode of green agriculture.


Author Correction: Different influences of facial attractiveness on judgments of moral beauty and moral goodness.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Morphological study of rib regeneration following costectomy in adolescent idiopathic scoliosis.
This is a prospective observational study comparing cases with retrospective controls. The aim of the study is to compare rib regeneration with a scaffold placed intra-periosteally against no scaffold, after costectomy in adolescent idiopathic scoliosis. A prospective study was conducted at Amrita Institute of Medical Sciences on 16 consecutive patients (51 ribs) with adolescent idiopathic scoliosis who underwent costectomy and application of gel foam in the rib bed as a scaffold. These patients were compared with a retrospective group of 15 patients (33 ribs) who did not have the scaffold. All prospective and retrospective patients were followed up for a minimum period of 6 months and were analyzed radiographically for rib regeneration and morphology. A classification system was devised to include all possible morphologies of regenerate. The resulting data, when analyzed showed that majority of ribs re-grew to normal morphology in 3-6 months in the trial group. In comparison the regeneration in the retrospective controls was slower and poorer in quality. Ribs treated by placement of gel foam scaffold in the bed regenerate to a near normal radiological profile within 6 months of costectomy compared to a slower regeneration in those without gel foam scaffold.


Astrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes.
Hypothalamic inflammation plays an important role in disrupting feeding behavior and energy homeostasis as well as in the pathogenesis of obesity and diabetes. Here, we show that pyruvate dehydrogenase kinase (PDK)-2 plays a role in hypothalamic inflammation and its sequelae in mouse models of diabetes. Cell type-specific genetic ablation and pharmacological inhibition of PDK2 in hypothalamic astrocytes suggest that hypothalamic astrocytes are involved in the diabetic phenotype. We also show that the PDK2-lactic acid axis plays a regulatory role in the observed metabolic imbalance and hypothalamic inflammation in mouse primary astrocyte and organotypic cultures, through the AMPK signaling pathway and neuropeptidergic circuitry governing feeding behavior. Our findings reveal that PDK2 ablation or inhibition in mouse astrocytes attenuates diabetes-induced hypothalamic inflammation and subsequent alterations in feeding behavior.


[Hearing loss determination and assessment of the reduction in earning capacity taking speech discrimination tests in noise into account].
In Germany the guideline for the hearing loss quantification and the resulting assessment of the reduction in earning capacity is the Königsteiner Merkblatt (KM). The quantification depends on the results of the tone and speech audiogram in silence. However, speech discrimination tests in noise may provide additional information about the impairment of the ENT patients. Especially, the impairment of persons with a slight hearing loss, characterized by high-frequency hearing loss, in noisy environment can not be indicated by the measurement in silence, which is proposed in the KM. METHODS UND PATIENTS: The Göttingen sentence test in noise was applied as a supplement to the routine ENT procedures of the medical estimate in 135 test persons. Based on these measurement results a table for the percentage hearing loss in noise is defined. Furthermore, an integration of the hearing loss in noise in the assessment of the reduction in earning capacity is proposed in addition to the hearing loss in silence. Using the newly introduced hearing loss for speech in noise, a suitable assessment for persons with a slight hearing loss is achieved. By integrating it into the assessment procedure additionally to the hearing loss in silence, the hearing impairment of all patients can be rated depending on their speech test results in silence and in noise. In comparison to the results obtained by the KM, the new procedure does not lead to higher values for the proposed reduction in earning capacity in general, but instead seems to be equally suitable for all groups of patients.


Epstein-Barr virus serology in the chronic fatigue syndrome.
The antibody profiles against Epstein-Barr virus were studied in 136 patients presenting with chronic fatigue syndromes. These profiles were compared with a panel of sera from blood donors. The patients exhibited higher titres in a combined assay for antibodies to the Restricted (R) and Diffuse (D) components of the Early Antigen complex than controls (P less than 0.001) but titres against these antigens were not useful on an individual patient basis. The patients who displayed elevated titres of antibodies to Early Antigens did not differ clinically from those displaying titres in the control range. Four of nine patients who had increased antibodies to Early Antigens also had evidence of active enterovirus infection.


Eimeria tenella: ginsenosides-enhanced immune response to the immunization with recombinant 5401 antigen in chickens.
Three-day-old specific-pathogen-free chickens were subcutaneously immunized with Eimeria tenella recombinant 5401 antigen (100 microg per chicken) with (0.25, 0.5 or 1.0mg per dose) or without ginsenosides, and boosted with the same dosage 14 days later. The chickens were challenged with 6 x 10(4) homologous sporulated oocysts 14 day after the booster. The specific antibody response and lymphocyte proliferation in response to Con A were measured before and 7, 14, 21, 28, 35, 42 days after the immunization. Oocyst output, mortality, and lesion scores were measured to evaluate the protective effects of the immunization. The vaccine containing 0.5 or 1.0mg ginsenosides per dose induces higher antibody response and lymphocyte proliferation in response to Con A than the vaccine without ginsenosides or containing 0.25mg per dose. The oocyst output indicated that recombinant 5401 antigen with ginsenosides (0.5 and 1.0mg per dose) gave a protection rate of 59.38 and 62.5%, respectively. The lesion score in the group vaccinated with recombinant 5401 antigen with 0.5 or 1.0mg ginsenosides per dose were significantly lower than in group without ginsenosides or containing 0.25mg per dose. Therefore, we conclude that ginsenosides have strong adjuvant effects at a dose of 0.5 or 1.0mg when mixed with E. tenella recombinant 5401 antigen, and has a potential as an adjuvant in chicken vaccine.


TiO2 nanoparticles enhanced bioaccumulation and toxic performance of PAHs via trophic transfer.
Engineering nanoparticles (NPs) could act as accumulator and carrier of co-contaminants, affecting their fate and toxicity in environments. However, the effects of NPs on the bioaccumulation and trophic transfer of co-contaminants through the food chain and the ensuing effects on higher predators are unclear. In the present study, we investigated the effects of titanium dioxide nanoparticles (nTiO2) on the trophic transfer of phenanthrene (Phe) from prey Artemia salina to predator Scophthalmus maximus. We also evaluated the ensuing toxic performance of Phe in S. maximus after been transferred from A. salina in the presence and absence of nTiO2. The presence of nTiO2 significantly (p < 0.05) increased Phe accumulation in A. salina with higher bioconcentration factor (BCF) up to 90.9 than that of 38.6 in Phe exposure along. After trophic transfer, nTiO2 (1 mg/L) also promoted the bioaccumulation of Phe (1 μg/L) in predator S. maximus from 4.17 mg/kg to 7.85 mg/kg (dry weight). However, nTiO2 did not enhance the trophic transfer of Phe from A. salina to S. maximus since the biological magnification factor (BMF) decreased from 0.13 to 0.08. Nevertheless, the nTiO2-enhanced bioaccumulation of Phe did enhance Phe toxicity performance in predator S. maximus after trophic transfer, showing significant (p < 0.05) growth inhibition and changes of nutrient status in the predator, compared to those of the control. Further physio-biochemical investigations suggested that oxidative stress and inhibition of digestive functions might explain the growth inhibition in treatment with nTiO2 + Phe. This study demonstrates the first evidence that NP-enhanced bioaccumulation and toxic performance of co-existing pollutants across trophic transfer, which poses potential risks to marine ecosystems, and ultimately human health by seafood consumption.


Open side-to-side repair for non-repairable tendon-to-bone rotator cuff tear. Clinical and anatomic outcome at a mean 5 years' follow-up.
Anatomical tendon-to-bone repair of retracted rotator cuff tear is a difficult challenge given the high rate of recurrence. The study hypothesis was that side-to-side repair of U-shaped retracted tear allows tendon healing with satisfactory medium-term clinical results. Between 1999 and 2007, 35 patients (mean age 53.5 years) were operated on with this open technique. On the De Orio and Cofield classification, tendon lesions were medium in 5 cases, large in 25 and massive in 5. Subacromial space was in all cases greater than 7 mm. Fatty infiltration grade was less than or equal to 2 on Goutallier's classification in all cases except for 1 grade3 (supraspinatus only). At last follow-up, patients were assessed clinically (Constant score) and radiographically. Tendon healing was assessed by ultrasound (31 cases) or CT-arthrography (4 cases). Mean follow-up was 60 months. Constant score improved significantly, from 64.7 ± 10 preoperatively to 77.1 ± 14 postoperatively (P < 0.05). Recurrence rate was 17.1%. Subacromial space was < 6 mm postoperatively in 2 cases. Side-to-side repair, bringing the posterior cuff onto the anterior edge of the tear, allowed tension-free repair of retracted tear if the preoperative reparability criteria are met: subacromial space equal to or greater than 7 mm, and absence of fatty infiltration significantly greater than grade 2 on the Goutallier classification. Under these conditions, clinical and anatomical results were satisfactory at a mean 5 years' follow-up. IV, retrospective.


Electrocardiographic manifestations and in-hospital prognosis of transient acute myocardial ischemia at rest.
From January 1970 to June 1985, transient electrocardiographic changes at rest were documented in 652 patients admitted to our coronary care unit. Patients were stratified according to the type of electrocardiographic alteration at rest: 295 had ST-segment elevation (group 1), 106 T-wave changes (group 2) and 251 ST-segment depression (group 3). Patients in group 3, compared with groups 1 and 2, were more likely to have symptoms of coronary artery disease dating back many years (p less than 0.01 and p less than 0.01, respectively), a previous myocardial infarction (p less than 0.05 and difference not significant), a positive exercise test (p less than 0.01 and p less than 0.01), transient ST-T changes occurring in a higher number of electrocardiographic leads (p less than 0.01 and p less than 0.01), multivessel disease (p less than 0.001 and p less than 0.01) and poor ventricular function (p less than 0.01 and p less than 0.05). Despite these differences, the occurrence of acute myocardial infarction and cardiac death during hospitalization was much more frequent in group 1 compared with groups 2 (p less than 0.02) and 3 (p less than 0.05). However, death occurred in those patients who had poor ventricular function and severe atherosclerosis. A greater susceptibility of group 1 patients to severe vasoconstriction documented by the ergonovine test and by the occurrence of spontaneous spasm seems to account for different in-hospital outcome.


Induction and isolation of mutants in fungi at low mutagen doses.
Since the yield of mutants per surviving cell increases in general with increasing dose of mutagen, it has often been concluded in the literature that it is the most efficient to apply high mutagen doses so that most spores are killed. As high doses of mutagen produce chromosome rearrangements and unnoticed mutations which disturb the genetic background, the relationship between mutant frequency and survival was analyzed with Aspergillus nidulans as a model. It is shown that for different types of mutants the highest mutant yield is obtained at low mutagen doses (20-50% survival). Mutant frequency increases with increasing dose of mutagen but levels off and even decreases at higher dosages. There is no simple linear relationship between mutant frequency and the logarithm of the mutagen dose or the logarithm of the surviving fraction. If appropriate enrichment procedures are also available auxotrophic mutants can best be isolated at low doses of mutagen. Taking into account the disturbance of the genetic background, mutation induction should be done preferentially at a survival level of at least 70%.


Effect of ICD-9 to ICD-10 Transition on Accuracy of Codes for Stage of Diabetic Retinopathy and Related Complications: Results from the CODER Study.
When the International Classification of Diseases 9th Revision (ICD-9) transitioned to the International Classification of Diseases 10th Revision (ICD-10), there was a marked increase in the complexity of International Classification of Diseases (ICD) codes with potential for improved specificity in clinical database research. The purpose of this study was to characterize the accuracy of coding for stage of diabetic retinopathy (DR) and DR-related complications (including vitreous hemorrhage, retinal detachment, and neovascular glaucoma) during this transition. Retrospective chart review of 3 time periods corresponding to the use of ICD-9: 2014-2015; "early" use of ICD-10, 2015-2016; and "late" use of ICD-10, 2018-2019. Patients aged 18 years or older with a diagnosis of DR at a multispecialty academic institution. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and kappa (κ) statistics were generated for each diagnosis. Generalized estimating equation (GEE) models were used to assess the significance of the variables. The main outcome was the proportion of agreement between the ICD code and the documented chart standard for stage of DR and DR-related complications. A total of 600 patients were included in the study (average age, 61 years; range, 25-93 years). Overall, there was substantial agreement between the ICD codes for stage of DR and the documented standard (κ = 0.66). The proportion of ICD codes in agreement with the documented standard diagnosis increased with time: 66.5%, 78.5%, and 83.3% for ICD-9, "early" ICD-10, and "late" ICD-10, respectively. The odds of agreement were 2.67 (95% confidence interval [CI], 1.49-4.76, P < 0.001) and 3.96 (95% CI, 2.34-6.69, P < 0.0001) times greater for "early" and "late" ICD-10 codes compared with ICD-9 codes, respectively. For specific codes, the overall PPV, NPV, sensitivity, and specificity for nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were excellent (>90%). The odds of agreement were 19.70 (95% CI, 11.54-33.64, P < 0.0001) times greater for PDR than NPDR. Compared with the stage of DR, DR-related diagnoses were overall less accurately coded (κ = 0.61, 0.48, and 0.52 for vitreous hemorrhage, retinal detachment, and neovascular glaucoma, respectively). Coding in ICD-10 is more accurate than in ICD-9, particularly for PDR compared with NPDR. The increased accuracy emphasizes the potential for ICD-10 coding to be used effectively in database research.


[Effect of calcium antagonists verapamil and amlodipine on the risk of development of atrial fibrillation after coronary artery bypass grafting].
To assess effect of calcium antagonists amlodipine and verapamil on the risk of development of atrial fibrillation after coronary artery bypass surgery. Of 74 patients subjected to mammary artery and venous coronary bypass grafting with the use of cardiopulmonary bypass 19 received amlodipine and 21 - verapamil. Attacks of atrial fibrillation during 24 hour ECG monitoring were registered in 22.9% of patients mostly on days 2 and 3 after surgery. In verapamil treated patients atrial fibrillation occurred 1.5-2 times more often than in amlodipine treated patients or in patients receiving no calcium antagonists. This could possibly be explained by pronounced slowing of atrio-ventricular conduction by verapamil at the background of postoperative general "irritation" of the atrial myocardium.