Immobilization of zinc and cadmium by biochar-based sulfidated nanoscale zero-valent iron in a co-contaminated soil: Performance, mechanism, and microbial response.
Mining and smelting of mineral resources causes excessive accumulation of potentially toxic metals (PTMs) in surrounding soils. Here, biochar-based sulfidated nanoscale zero-valent iron (SNZVI/BC) was designed via a one-step liquid phase reduction method to immobilize cadmium (Cd) and zinc (Zn) in a copolluted arable soil. A 60 d soil incubation experiment revealed that Cd and Zn immobilization efficiency by 6 % SNZVI/BC (25.2-26.2 %) was higher than those by individual SNZVI (13.9-18.0 %) or biochar (14.0-19.3 %) based on the changes in diethylene triamine pentaacetic acid (DTPA)-extractable PTM concentrations in soils, exhibiting a synergistic effect. Cd2+ or Zn2+ replaced isomorphously Fe2+ in amorphous ferrous sulfide, as revealed by XRD, XPS, and high-resolution TEM-EDS, forming metal sulfide precipitates and thus immobilizing PTMs. PTM immobilization was further enhanced by adsorption by biochar and oxidation products (Fe2O3 and Fe3O4) of SNZVI via precipitation and surface complexation. SNZVI/BC also increased the concentration of dissolved organic carbon and soil pH, thus stimulating the abundances of beneficial bacteria, i.e., Bacilli, Clostridia, and Desulfuromonadia. These functional bacteria further facilitated microbial Fe(III) reduction, production of ammonium and available potassium, and immobilization of PTMs in soils. The predicted function of the soil microbial community was improved after supplementation with SNZVI/BC. Overall, SNZVI/BC could be a promising functional material that not only immobilized PTMs but also enhanced available nutrients in cocontaminated soils.


The effectiveness of mindfulness-based cognitive therapy for major depressive disorder: evidence from routine outcome monitoring data.
Meta-analyses show efficacy of mindfulness-based cognitive therapy (MBCT) in terms of relapse prevention and depressive symptom reduction in patients with major depressive disorder (MDD). However, most studies have been conducted in controlled research settings. We aimed to investigate the effectiveness of MBCT in patients with MDD presenting in real-world clinical practice. Moreover, we assessed whether guideline recommendations for MBCT allocation in regard to recurrence and remission status of MDD hold in clinical practice. This study assessed a naturalistic cohort of patients with (recurrent) MDD, either current or in remission (n = 765), who received MBCT in a university hospital out-patient clinic in The Netherlands. Outcome measures were self-reported depressive symptoms, worry, mindfulness skills and self-compassion. Predictors were MDD recurrence and remission status, and clinical and sociodemographic variables. Outcome and predictor analyses were conducted with linear regression. MBCT adherence was high (94%). Patients with a lower level of education had a higher chance of non-adherence. Attending more sessions positively influenced improvement in depressive symptoms. Depressive symptoms significantly reduced from pre- to post-MBCT (Δ mean = 7.7, 95%CI = 7.0-8.5, Cohen's d = 0.75). Improvement of depressive symptoms was independent from MDD recurrence and remission status. Unemployed patients showed less favourable outcomes. Worry, mindfulness skills and self-compassion all significantly improved. These improvements were related to changes in depressive symptoms. Previous efficacy results in controlled research settings are maintained in clinical practice. Results illustrate that MBCT is effective in routine clinical practice for patients suffering from MDD, irrespective of MDD recurrence and remission status.


The genome sequence of the black needle fly, Leuctra nigra (Olivier, 1811).
We present a genome assembly from an individual male Leuctra nigra (black needle fly; Arthropoda; Insecta; Plecoptera; Leuctridae). The genome sequence is 536.3 megabases in span. Most of the assembly is scaffolded into 13 chromosomal pseudomolecules , including the X sex chromosome. The mitochondrial genome has also been assembled and is 17.6 kilobases in length.


Cost savings from use of emergency contraceptive pills in Australia.
Emergency contraception, which prevents pregnancy after unprotected sexual intercourse, has the potential to reduce significantly the incidence of unintended pregnancy and the consequent need for abortion and to reduce medical care costs. To determine the savings generated by use of Postinor-2, the levonorgestrel regimen of emergency hormonal contraception, in Australia. We modelled the cost savings when women obtain Postinor-2 directly from a pharmacist where cost savings are measured as the cost of pregnancies averted by use of Postinor-2 per dollar spent on Postinor-2. Each dollar spent on a single treatment with Postinor-2 saves A$2.27-A$3.81 in direct medical care expenditures on unintended pregnancy depending on assumptions about savings from costs avoided by preventing mistimed births. Postinor-2 is cost-saving even under the least favourable assumption that mistimed births when prevented today occur 2 years later. Results are robust even to large changes in model input parameters. Emergency contraception is cost saving. More extensive use of emergency contraception could save considerable medical and social costs by reducing unintended pregnancies, which are expensive.


Safety parameters of ferromagnetic device during thyroid surgery: Porcine model using continuous neuromonitoring.
The ferromagnetic (FM) device is a new surgical energy modality. This study investigated dynamic recurrent laryngeal nerve (RLN) electromyographic (EMG) data to define safety parameters for using FM devices in thyroidectomy. Real-time EMG tracings obtained under continuous neuromonitoring were recorded from 24 RLNs (12 piglets). In the activation study, FM devices were activated at varying distances from the RLN. In the cooling study, FM devices were cooled for varying time intervals, or muscle touch maneuver was performed, before contact with the RLN. During the FMwand/FMsealer activation, no adverse EMG events occurred at distances of 2 mm or longer. The cooling study revealed no adverse EMG events after 1-second (FMwand) or 3-second (FMsealer) intervals or after muscle touch maneuver. An FM device should be activated at a distance of 2 mm from the RLN and should be adequately cooled before further contact with the RLN. Surgeons can avoid RLN injury by observing standard procedures for using FM devices.


Characterization of the unique oral microbiome of children with Down syndrome.
Down syndrome creates an abnormal oral environment, including susceptibility to periodontal disease at a young age, but there are no detailed studies of the oral microbiome in children with Down syndrome. In this study, we performed a comprehensive analysis of the oral bacteria of 40 children with Down syndrome and 40 non-Down syndrome children. Microbial DNA was extracted from dental plaque specimens and the V4 hypervariable region of the bacterial 16S rRNA gene was analyzed using the MiSeq platform. There were significant differences between the Down syndrome and non-Down syndrome groups in mean numbers of operational taxonomic units, and α- and β-diversity (P < 0.05). Interestingly, significant differences in α- and β-diversity between the two groups were only observed in subjects with gingival inflammation, but not in those without gingival inflammation (P < 0.05). Taxonomic analysis at the genus or species levels showed significant differences in relative abundance levels of certain bacteria between the Down syndrome and non-Down syndrome groups, including Corynebacterium, Abiotrophia and Lautropia (P < 0.05). These results suggest that children with Down syndrome may have a unique oral microbiome that could impact the development of dental diseases common in people with the syndrome.


Ultrastructural correlates of experimentally altered transmitter release efficacy in frog motor nerve terminals.
After experimentally inducing long term changes in transmitter release, a series of frog neuromuscular junctions were studied with intracellular recording and then semi-serially sectioned and examined in the electron microscope. Transmitter release per unit length of motor nerve terminal was well correlated with several measures of the length of individual presynaptic active zones and with the number of mitochondria per terminal. Total release from each terminal correlated with estimates of the total amount of active zone. This study of neuromuscular junctions in sartorius muscles of the frog Rana pipiens was undertaken to search for ultrastructural correlates of the increase in transmitter release efficacy that follows denervation of the contralateral sartorius. This treatment typically results in greatly enhanced release at some synapses while others appear unaffected. In the present study, nine identified junctions with known physiological properties were sectioned every 6 micron throughout much of their length to yield 40-105 cross-sectional profiles per junction. Overall, these 9 synapses showed a 33-fold range in quantal transmitter release and an 18-fold range in release per unit nerve terminal. Release correlated with estimates of active zone size. No correlations were found between release and the density of synaptic vesicles adjacent to active zones. Our results suggest that active zones in motor nerve terminals are plastic structures, and that changes in active zone size may be the structural basis of long term changes in transmitter release and synaptic efficacy.


Recanalization and particle exclusion after embolization of uterine arteries in sheep: a long-term study.
To compare the long-term evolution of uterine arteries after embolization with the two most commonly used embolic agents for fibroid embolization: nonspherical polyvinyl alcohol (PVA) particles and trisacryl gelatin microspheres (TGMS). Prospective study. University-based interventional radiology, pathology, and reproductive physiology units. Two groups of 10 sheep embolized in the uterine artery. Embolization of the uterine artery with either 600-1000 microm nonspherical polyvinyl alcohol (PVA) particles or with 700-900 microm trisacryl gelatin microspheres (TGMS). Animals were synchronized and naturally inseminated. Animals were killed at 26 months. Uteri were examined pathologically for vessel size, site of occlusion, recanalization rate of vessels, and particle location within the vascular wall. The PVA particles were more numerous in the vessels' lumen than the TGMS particles (13.3 +/- 20.8 vs. 2.5 +/- 2.7), were located more proximally than TGMS (97% vs. 68% in the trunk and first branches of the uterine artery), and were found almost exclusively in the intima (99.2%). In contrast, 54.4% of the TGMS particles were found in the intima, and 45.6% partially or totally excluded. The rate of recanalization was not statistically significantly different for PVA and TGMS (65.2% vs. 60.6%). The long-term evolution of uterine arteries was different after uterine artery embolization with PVA and TGMS because PVA particles formed large-sized aggregates that occluded proximal vessels and remained in the vessel intima. Microspheres occluded more distal vessels, and about 50% of them were partially or totally excluded from the vessel.


Reliability of peripheral intraneural microhemodynamics evaluation by using contrast-enhanced ultrasonography.
The purpose of the study was to validate the reliability of quantitative intraneural enhancement patterns by using contrast-enhanced ultrasonography (CEUS). Nine asymptomatic wrists underwent a total of three CEUS examinations each conducted at 1-month intervals. The CEUS enhancement pattern of median nerves was quantitatively evaluated. The area under the time-intensity curve was calculated by placing the regions of interest at the proximal, center, and distal regions of the median nerve. An intra-class correlation coefficient for intra-observer, inter-observer, and inter-examination reproducibility was calculated. The intra- and inter-observer reproducibility was almost perfect. Inter-examination reproducibility of the proximal, center, and distal regions was 0.891, 0.614, and 0.535, respectively. In this study, we found that the reproducibility of the distal and center regions of the median nerve in the carpal tunnel was lower than that of the proximal region. High intra-observer, inter-observer, and inter-examination reproducibility of CEUS was obtained in the evaluation of the intraneural enhancement pattern when the region of interest was placed in the proximal region of the median nerve.


Chronic elbow instability.
Chronic elbow instability without fractures in adults can be broken down into three types: (1) valgus instability, (2) posterolateral rotator instability, and (3) isolated radial head instability. By far the most common is valgus instability, which usually occurs in throwing athletes as a result of repetitive microtrauma to the anterior band of the medial collateral ligament. Surgical treatment is aimed at reconstruction of the anterior band of the medial collateral ligament. Posterolateral rotatory instability is much less common and is diagnosed by the lateral pivot-shift test of the elbow. It is usually the result of an undiagnosed acute injury to the lateral ulnar collateral ligament. Surgical treatment is aimed at its reconstruction. Isolated radial head subluxation in adults is extremely rare. The essential lesion is a disruption of the annular ligament. Surgical treatment is either radial head resection or reconstruction of the annular ligament.


Curcumin inhibits aerobic glycolysis in hepatic stellate cells associated with activation of adenosine monophosphate-activated protein kinase.
Activation of hepatic stellate cells (HSCs) is characterized by expression of extracellular matrix and loss of adipogenic phenotype during liver fibrogenesis. Emerging evidence suggests that HSCs adopt aerobic glycolysis during activation. The present work aimed at investigating whether the anti-fibrogenic effects of curcumin was associated with interfering with glycolysis in HSCs. Primary rat HSCs were cultured in vitro. We demonstrated that inhibition of glycolysis by 2-deoxyglucose or galloflavin reduced the expression of α-smooth muscle actin (α-SMA) and α1(I)procollagen at both mRNA and protein levels, and increased the intracellular lipid contents and upregulated the gene and protein expression of adipogenic transcription factors C/EBPα and PPAR-γ in HSCs. Curcumin at 20 μM produced similar effects. Moreover, curcumin decreased the expression of hexokinase (HK), phosphofructokinase-2 (PFK2), and glucose transporter 4 (glut4), three key glycolytic parameters, at both mRNA and protein levels. Curcumin also reduced lactate production concentration-dependently in HSCs. Furthermore, curcumin increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), but AMPK inhibitor BML-275 significantly abolished the curcumin downregulation of HK, PFK2, and glut4. In addition, curcumin inhibition of α-SMA and α1(I)procollagen was rescued by BML-275, and curcumin upregulation of C/EBPα and PPAR-γ was abrogated by BML-275. These results collectively indicated that curcumin inhibited glycolysis in an AMPK activation-dependent manner in HSCs. We revealed a novel mechanism for curcumin suppression of HSC activation implicated in antifibrotic therapy. © 2016 IUBMB Life, 68(7):589-596, 2016.


The anti-adhesive and anti-invasive effects of recombinant azurin on the interaction between enteric pathogens (invasive/non-invasive) and Caco-2 cells.
Anti-adhesion therapy and anti-adhesin immunity are meant to diminish the interaction between pathogens and host tissues, either by prevention or by exclusion of bacterial adhesion and entrance to cells. Azurin is a scaffold protein possessing antiviral, antiparasitic, and anticancer activities. The purpose of the present study was to determine the effect of recombinant Azurin (rAzurin) on the adhesion and invasion capacity of invasive (Shigella sonnei, Shigella flexneri, Campylobacter jejuni) and non-invasive (Vibrio cholerae) enteric bacteria to cells. The non-toxic dose of rAzurin and the best MOI (Multiplicity of Infection) of bacterial species was assessed by MTT assay. Bacterial species were used at MOIs of 20:1 and Azurin was applied at the concentrations of 5 and 25 μg/mL and added to Caco-2 cells in competition and replacement assay to assess the anti-adhesion and anti-invasion properties of rAzurin. The protein caused significant decrease in the adhesion rate of S. sonnei, S. flexneri, C. jejuni, and V. cholerae strains to Caco-2 cells by 43, 39, 72, and 38% in competition and 45, 46, 75, and 48% in replacement assays, respectively. Also, S. sonnei, S. flexneri, and C. jejuni strains invasion rate was reduced to 50, 50, and 70% in anti-invasion assay, respectively. The inhibitory effect of Azurin against C. jejuni and V. cholerae strains adhesion was more significant (p < .001) compared to Shigella spp. (p < .05) which may be due to smaller size of the former bacteria. On the contrary, in invasion assay, rAzurin showed a greater inhibitory effect against Shigella spp. (p < .001) compared to C. jejuni (p < .05), which may probably be due to the interaction of rAzurin with several effectors or ligands, involved in Shigella invasion and internalization. The findings of the present study opens new insights of rAzurin as a new and potent candidate for reducing or probably preventing enteric bacterial attachment, invasion, and pathogenesis.


Distribution of plasma vitamin E levels in supplemented very low birthweight infants.
The distribution of plasma Vitamin E (VE) was determined in 25 very low birthweight (VLBW) infants who were supplemented with 100 mg/kg per day of alpha-tocopherol acetate, given intragastrically. Their mean birthweight was 917 g and mean gestational age was 28 weeks. Mean plasma VE levels after 1 and 6 weeks' supplementation were 2.7 mg/dL (s.e.m. = 1.0) and 6.4 mg/dL (s.e.m. = 1.4), respectively (the difference was not significant). There was wide variability in plasma VE levels in these infants despite being on an identical dose of tocopherol. Plasma VE was less than 0.5 mg/dL in 12% of samples, 0.5-3.0 mg/dL in 32%, 3.1-5.0 mg/dL in 18%, and 5.1-20 mg/dL in 38%. Fifteen of the 25 infants had at least one level in the range which has been associated with an increased incidence of septicaemia and necrotizing enterocolitis (greater than 5.0 mg/dL). These data suggest that if a policy of VE supplementation for VLBW infants is chosen, monitoring of plasma VE levels appears necessary so that the dosage can be adjusted in order to maintain plasma VE within the optimal range. This study's dosage regimen of supplementing infants with 100 mg/kg per day of VE was associated with a high incidence of elevated plasma VE levels and it is concluded that it is not advisable to use such large doses of VE in the premature newborn.


Targeted mRNA demethylation in Arabidopsis using plant m6A editor.
N6-methyladenosine (m6A) is an important epigenetic modification involved in RNA stability and translation regulation. Manipulating the expression of RNA m6A methyltransferases or demethylases makes it difficult to study the effect of specific RNA methylation. In this study, we report the development of Plant m6A Editors (PMEs) using dLwaCas13a (from L. wadei) and human m6A demethylase ALKBH5 catalytic domain. PMEs specifically demethylates m6A of targeted mRNAs (WUS, STM, FT, SPL3 and SPL9) to increase mRNAs stability. In addition, we discovered that a double ribozyme system can significantly improve the efficiency of RNA editing. PMEs specifically demethylates m6A of targeted mRNAs to increase mRNAs stability, suggesting that this engineered tool is instrumental for biotechnological applications.


Human Genetic Variants Associated with COVID-19 Severity are Enriched in Immune and Epithelium Regulatory Networks.
Human genetic variants can influence the severity of symptoms infected with SARS-COV-2. Several genome-wide association studies have identified human genomic risk single nucleotide polymorphisms (SNPs) associated with coronavirus disease 2019 (COVID-19) severity. However, the causal tissues or cell types underlying COVID-19 severity are uncertain. In addition, candidate genes associated with these risk SNPs were investigated based on genomic proximity instead of their functional cellular contexts. Here, we compiled regulatory networks of 77 human contexts and revealed those risk SNPs' enriched cellular contexts and associated risk SNPs with transcription factors, regulatory elements, and target genes. Twenty-one human contexts were identified and grouped into two categories: immune cells and epithelium cells. We further aggregated the regulatory networks of immune cells and epithelium cells. These two aggregated regulatory networks were investigated to reveal their association with risk SNPs' regulation. Two genomic clusters, the chemokine receptors cluster and the oligoadenylate synthetase (OAS) cluster, showed the strongest association with COVID-19 severity, and they had different regulatory programs in immune and epithelium contexts. Our findings were supported by analysis of both SNP array and whole genome sequencing-based genome wide association study (GWAS) summary statistics. The online version contains supplementary material available at 10.1007/s43657-022-00066-x.


Failure of allopurinol and a spin trapping agent N-t-butyl-alpha-phenyl nitrone to modify significantly ischaemia and reperfusion-induced arrhythmias.
The possible role of free radicals in the genesis of occlusion and reperfusion-induced arrhythmias was studied by determining the effects of the xanthine oxidase inhibitor allopurinol (400 mg p.o. 24 h before experimentation +25 mg kg-1 i.v.) and the free radical scavenger N-t-butyl-alpha-phenyl nitrone (PBN; 50 mg kg-1 i.v.) on these arrhythmias in chloralose anaesthetized greyhounds. Neither of the drugs had any major effects on haemodynamic variables, although allopurinol caused a significant increase in heart rate. The mean number of extrasystoles observed during ischaemia in dogs given allopurinol or PBN was not significantly different from those seen in controls. Further, the incidence of ventricular fibrillation during either occlusion or reperfusion was unchanged by either drug and there was thus no improvement in survival. These results suggest that, in this model of myocardial ischaemia and reperfusion, free radicals may not play a major role in the genesis of life-threatening arrhythmias.


Fronto-basal interhemispheric approach for craniopharyngiomas extending outside the suprasellar cistern.
The aim of the present study was to establish the usefulness of the fronto-basal approach with a relatively small craniotomy window for the removal of tumors protruding from the sellar-suprasellar region to the third and basal cistern. Forty-two patients who were surgically treated for craniopharyngiomas extending outside the sellar-suprasellar region were evaluated. All the patients were operated on by the fronto-basal interhemispheric approach, and the average follow-up period was 5 years. Gross total resection of the lesion was achieved in 30 cases. Eight patients underwent subtotal resection and four patients underwent partial removal due to recurrence after previous surgeries with or without radiotherapy. In the immediate postoperative period, major complications, including impairment of the cranial nerves, were observed in two cases. One patient exhibited transient memory disturbance due to infarction of the perforator; after 3 months, this symptom was ameliorated. Three of the patients died during follow-up; however, 6 of the 30 undergoing gross total removal and 10 of the 12 patients undergoing subtotal or partial removal suffered regrowth. Ultimately, a total of 12 patients underwent re-operation with the same approach or combined with the orbito-zygomatic approach. In our experience, the fronto-basal interhemispheric approach, even through a small craniotomy window, is a valid choice for the removal of craniopharyngiomas extending outside the sellar-suprasellar region. Using this approach, tumors can be removed without significant sequelae related to surgical technique due to easy preservation of the pituitary stalk, hypothalamic structures, and perforators. This approach offers a safe and minimally invasive means of treating craniopharyngiomas.


Persistent trigeminal artery-superior cerebellar artery segmental fusion diagnosed using magnetic resonance angiography.
To describe a case of persistent trigeminal artery (PTA)-superior cerebellar artery (SCA) segmental fusion incidentally diagnosed on magnetic resonance (MR) angiography. A 53-year-old woman with a history of facial pain underwent cranial MR imaging and MR angiography. MR angiography showed a left lateral-type PTA arising from the precavernous portion of the left internal carotid artery (ICA). PTA branched into the left distal SCA and showed segmental fusion with the proximal SCA at the distal part of the PTA. We also diagnosed an unruptured cerebral aneurysm at the junction between the left ICA and PTA. PTA is the most frequent type of carotid-vertebrobasilar anastomosis. The reported prevalence rate is 0.2% by angiography and 0.34% by MR angiography. There are two types of PTA-lateral (usual) and medial (intrasellar). SCA arising from the lateral-type PTA has rarely been reported. Further, a PTA from which the distal SCA branches and segmentally fuses with the proximal SCA at the distal part of the PTA has not been reported. Using MR angiography, we diagnosed a rare type of PTA that fused segmentally with SCA. No similar case has been reported in relevant English-language literature.


Altered transitional circulation in infants of diabetic mothers with strict antenatal obstetric management: a functional echocardiography study.
Infants born to diabetic mothers (IDMs) even with good glycemic control are at risk for neonatal morbidity. Many of these problems occur during neonatal transition. We assessed (i) systemic and pulmonary blood flow in IDMs compared with controls and (ii) directional blood flow changes within fetal shunts during the first few days of life. In this prospective observational cohort study, we evaluated right (RVO) and left ventricular output, superior vena cava flow, atrial and ductal shunts, and tricuspid regurgitation in 32 IDMs and 18 controls using serial echocardiography after birth and 48 h of life in both groups and at 24 and 72 h in IDMs only. IDMs had lower RVO after birth and 48 h of life. IDMs also had less left to right atrial shunt and more right to left ductal shunt after birth compared with controls. In all, 15 of the 32 IDMs were admitted to the neonatal intensive care unit and 11 had respiratory symptoms. Persistence of fetal shunts and decreased RVO in IDMs suggest that even those with good gestational control have impaired transitional hemodynamics.


Statistical media optimization and cellulase production from marine Bacillus VITRKHB.
Marine Bacillus species are potent producers of novel enzymes. Marine Bacillus VITRKHB was observed to be efficient for cellulolytic activity. It was employed for the production of extracellular cellulase. Cellulase was partially purified to 1.6-fold in a stepwise manner by ammonium sulfate precipitation, dialysis, and DEAE ion exchange chromatography. The molecular weight of purified protein was found to be about 33 kDa by SDS-PAGE. Its specific activity was recorded as 1.92 IU/mg. The effect of various carbon and nitrogen sources on cellulase production was investigated. The maximum enzyme activity was recorded in the fermentation media containing xylose as carbon source and beef extract as nitrogen source. The combined interactive effect of different variables on cellulase production was studied by response surface methodology. The optimized combination of variables for maximum enzyme activity was determined as; xylose 5.0 %, beef extract 6.9 %, pH 7.83, NaCl 1.17, and temperature 25.84 °C, after 24 h of incubation.


Evaluation of degradation behavior over tetracycline hydrochloride by microbial electrochemical technology: Performance, kinetics, and microbial communities.
Tetracycline hydrochloride (TCH), as a typical antibiotic-pollutant, is desired to enhance its removal from public environment, due to its toxicity and persistence. Microbial electrochemical technology (MET) is a series complex microorganisms-driven processes with characteristics of simultaneous wastewater treatment and electricity generation. The study was presented to evaluate the TCH removal behavior and power generation performance through the co-metabolism under constant glucose with different TCH concentrations using MET. It was found that the TCH removal efficiency arrived at 40% during the first 6 h, when TCH concentrations ranged from 1 to 50 mg/L. It was interesting that TCH degradation rate increased to a maximum of 4.15 × 10-2 h-1 with its concentrations varying from 1 to 20 mg/L, however, the further increase to 50 mg/L in TCH concentration resulted in a reverse 66% reduction. In the meantime, the generated bioelectricity declared a similar fluctuation trend with a maximum power density of 600 mW/m2 under the condition of 20 mg/L TCH co-degradation with glucose. What's more, the TCH inhibition effect fitted well with Haldane's model, indicating that the microbial electrochemical system had a better potency toward TCH toxicity than that reported (EC50 = 2.2 mg/L). Thauera as mainly functional aromatics-degrading bacteria and Bdellovibrio against bacterial pathogens, only existed in the mixed cultures with TCH and glucose, indicating extremely remarkable changes in bacterial community with TCH addition. In summary, a new approach for the anaerobic biodegradation of TCH was explored through co-metabolism with glucose using MET. The results should be useful for antibiotics wastewater disposal of containing TCH.


Successful Single-Stage Operation for Loeys-Dietz Syndrome With Critical Coarctation of the Descending Aorta in a Young Adult.
Patients with critical coarctation of the aorta complicated with Loeys-Dietz syndrome are extremely rare. We report a successful single-stage operation involving critical coarctation of the descending aorta with a bicuspid aortic valve, aneurysmal aortic root, and ascending aorta in a 19-year-old man. The patient was genetically evaluated and a novel heterozygous TGFBR2 mutation was detected.


pH-dependent ileocolonic drug delivery, part II: preclinical evaluation of novel drugs and novel excipients.
Novel drugs and novel excipients in pH-dependent ileocolonic drug delivery systems have to be tested in animals. Which animal species are suitable and what in vivo methods are used to verify ileocolonic drug delivery?


Determination of hemoglobin adduct levels of the carcinogen 2,4-diaminotoluene using gas chromatography-electron impact positive-ion mass spectrometry.
A procedure to determine hemoglobin adduct yields resulting from exposure to the carcinogen 2,4-diaminotoluene (2,4-TDA) was developed using gas chromatography-electron impact positive-ion mass spectrometry. Liberated 2,4-TDA was quantified following alkaline hydrolysis of hemoglobin. Optimized derivatization of free 2,4-TDA with hepatafluorobutyric anhydride allowed detection of hemoglobin adduct levels as low as 5 ng/g Hb. Pure HFBA-2,4-TDA showed a linear dynamic range of 50 to 5000 pg. The quantitative extraction and recovery of liberated 2,4-TDA (ca. 100%) following hemoglobin hydrolysis allows accurate and precise determinations of adduct yields.


Effects of age and sex on bone density in the rhesus monkey.
Normative data for bone density of cortical and trabecular bone in the rhesus monkeys is described in the present study. Changes of bone density (g/cm2) for the humerus, the third lumbar vertebra, and the eighth caudal vertebra of the rhesus monkey show differences due to age and sex of the subjects (males n = 57; females n = 49). In general, bone density increased with age and then reached a plateau at approximately 3 to 4 years in all bones measured. In the humerus, older females (greater than 30 years) had a significantly lower bone density than females of 4 to 24 years, while bone density in older males did not decrease. In the vertebrae, some evidence of advanced age-related decreases in bone density was found in both sexes. These results indicate that the rhesus monkey shows a natural pattern of change in bone mineralization which parallels that seen in humans. The physiological similarity between the rhesus monkey and human further suggests a potential role for this species in the future investigation of osteoporosis.


Cirrhotic pleural effusion in the absence of ascites.
A 61-year-old female presented with a right transudative pleural effusion in the absence of ascites and other stigmata of chronic liver disease. A diagnosis of cirrhosis with a secondary hydrothorax was eventually established; however, ascites could never be demonstrated clinically or radiographically until just before her death, when hypertonic saline was administered for symptomatic hyponatremia. Based on the autopsy finding of a 1-mm hole in the right diaphragm and her clinical course, a mechanism for the production of a cirrhotic pleural effusion in the absence of asictes is proposed.


Estimation of the methylating capacity of the pineal gland. With special reference to indole metabolism.
In order to obtain more information on the methylating capacity of the pineal gland, a method determining the formation of different 5-methoxyindoles in the pineal gland was developed. The method depends on measuring the incorporation of labelled methyl groups into the various hydroxyindoles present in the pineal gland, after incorporation of pineal tissue with labelled S-adenosyl methionine. Hydroxyindoles were not added to the incubation medium. After incubation thin-layer chromatography was performed with pineal tissue together with the incubation medium; the spots were scraped and counted.


Isolation of 48 genetic markers appropriate for high throughput genotyping of inbred rat strains by B1 repetitive sequence-representational difference analysis.
Mapping of genetic suppressors, modifiers, and quantitative trait loci (QTLs) requires genetic markers that can be efficiently and inexpensively genotyped for a large number of individuals. To isolate rat genetic markers suitable for this purpose, representational difference analysis (RDA) was performed with amplicons prepared by PCR with the B1 repetitive sequence used as the primer (B1-amplicons). In total, 48 polymorphic DNA fragments were isolated by five series of RDA, subtracting the B1-amplicons prepared from an ACI/N (ACI) rat from those prepared from BUF/Nac (BUF), and vice versa. All the polymorphic fragments detected "presence-or-absence" polymorphisms with B1-amplicons prepared from ACI, BUF, and their F2 progeny, and each fragment was linkage mapped. Dot-blotting amplicons onto filters at a high density and hybridization of the filters with these B1-RDA markers made it possible to genotype a large number of rats simultaneously for multiple loci. These B1-RDA markers were polymorphic between two given inbred strains of rat at frequencies between 30% and 70%. This is the first report on the isolation of B1-RDA markers among inbred strains of rats.


Survey of neuropeptide-like immunoreactivity in supramedullary neurons of Coris julis (L.).
The supramedullary neurons of the marine teleost Coris julis (L.) were surveyed for neuropeptide-like immunoreactivity using antisera against 12 peptides. These neurons exhibit positive immunoreactivity to CCK-8, CCK-39 and gastrin(18-34). The presence of gastrin/CCK-like peptides in the supramedullary neurons is discussed.


ATP-induced, P2U purinoceptor-mediated constriction of isolated, perfused mesenteric beds of the rat.
alpha,beta-Methylene ATP (alpha, beta-mATP), ATP and UTP dose dependently increased the perfusion pressure of rat mesenteric arteries with a potency order of alpha, beta-mATP >> ATP > UTP. In the veins, while alpha, beta-mATP did not affect the pressure, both ATP and UTP equi-potently increased it. The arterial ATP response was attenuated to some degree by suramin (100 microM), but markedly and to a similar extent by pyridoxal-phosphate-6-azophenyl-2',4-disulphonic acid (PPADS 30 microM) and alpha, beta-mATP (100 nmol). The venous response was not affected by PPADS or alpha, beta-mATP, but was slightly attenuated by suramin. Thus, ATP seems to elicit arterial constriction predominantly by stimulating P2X, but venous constriction by stimulating P2U purinoceptors.


Invasive FFR and Noninvasive CFR in the Evaluation of Ischemia: What Is the Future?
This review provides an integrative and forward-looking perspective on the gamut of coronary physiology for the diagnosis and management of atherosclerosis. Because clinical events serve as the ultimate gold standard, the future of all diagnostic tests, including invasive fractional flow reserve and noninvasive coronary flow reserve, depends on their ability to improve patient outcomes. Given the prominent role of acute coronary syndromes and invasive procedures in cardiology, we practically consider 2 broad categories of patients with coronary disease: acute and stable. For patients with acute coronary disease, coronary physiology may potentially refine treatment of the culprit lesion. For both patients with stable and acute nonculprit disease, reducing hard endpoints with revascularization potentially occurs at the severe end of the focal physiological spectrum, an area under-represented in existing trials. Nonepicardial disease and diffuse atherosclerosis remain underexplored aspects of coronary physiology for testing of novel treatments.


Epidermoid inclusion cysts of the phalanx, radiological and clinical correlation.
A patient with an epithelial inclusion cyst of the distal phalanx has been presented. The radiographic and clinical findings have been described and are felt to be pathognomonic. The importance of recognizing its benign nature has been stressed.


Intermittent erection in spinal canal stenosis.
A case of intermittent erection in a patient with spinal canal stenosis is reported. The symptoms disappeared after lumbar laminectomy. The mechanism of erection remains speculative.


Stress ultrasound in baseball players with ulnar collateral ligament injuries: additional value for predicting rehabilitation outcome.
The purpose of this study was to evaluate the additional value of stress ultrasound (US) for predicting rehabilitation outcome in baseball players with ulnar collateral ligament (UCL) injury. Stress US and magnetic resonance imaging (MRI) in 41 baseball players with UCL injury who received rehabilitation treatment for more than 6 weeks were retrospectively compared between the rehabilitation group (n = 23) and surgery group (n = 18). The MRI grade of UCL injury was assessed as intact continuity, low-grade partial tear, high-grade partial tear, and complete tear. To estimate sonographic joint laxity, we assessed 3 sonographic criteria as present or absent: ligamentous waviness, joint gapping, and intra-articular ring-down artifact. In addition, the presence of concomitant tenderness was checked during stress US. The diagnostic validity of MRI with and without stress US was analyzed as a predictor for the rehabilitation outcome. The MRI grade was higher in the surgery group than in the rehabilitation group (P < .001). Sonographic joint laxity showing the ring-down artifact and concomitant tenderness with stress were significantly more frequent in the surgery group (P = .024 and P = .006, respectively). Sensitivity, specificity, and accuracy were 61.1%, 86.9%, and 75.6%, respectively, for MRI alone and 83.3%, 56.5%, and 68.2%, respectively, for the combination of MRI with joint laxity showing the ring-down artifact. For MRI in combination with joint laxity and concomitant tenderness, these values were 72.2%, 82.6%, and 78.0%, respectively. The addition of stress US showing the ring-down artifact and concomitant tenderness was helpful for predicting the rehabilitation outcome of UCL injuries.


Testing and implementing signal impact analysis in a regulatory setting: results of a pilot study.
Statistical signal detection methods such as proportional reporting ratios (PRRs) detect many drug safety signals when applied to databases of spontaneous suspected adverse drug reactions (ADRs). Impact analysis is a tool that was developed as an aid to prioritisation of such signals. This paper describes a pilot project whereby impact analysis was simultaneously introduced into practice in a regulatory setting and tested in comparison with the existing approach. Impact analysis was run on signals detected during a 26-week period from the UK Adverse Drug Reactions On-line Information Tracking (ADROIT) database of spontaneous ADRs that met minimum criteria (PRR>or=3.0, chi2>or=4.0 and >or=3 reported cases) and related to established drugs (i.e. those that have been available for at least 2 years and no longer carry the 'black triangle' symbol). The current method of signal prioritisation (i.e. the collective judgement at a weekly meeting) was initially performed without knowledge of the findings of impact analysis. Subsequently, the meeting was presented with the findings and, where appropriate, given the opportunity to reconsider the judgement made. The categories arising from the two methods were compared and the ultimate action recorded. Inter-observer variation between scientists performing impact analysis was also assessed. Eighty-six separate signals were analysed by impact analysis, of which 5% were categorised as high priority (A), 14% as requiring further information (B), 31% as low priority (C) and 50% as no action required (D). In general, the new method tended to give a higher level of priority to signals than the existing approach. Overall, there was 59% agreement between the impact analysis and the collective judgement at the meetings (kappa statistic=0.30). There was slightly greater agreement between impact analysis and the final action taken (kappa statistic=0.39), indicating that the findings of an impact analysis had an influence on the outcome. Assessment of inter-observer variation demonstrated that the method is repeatable (kappa statistic for overall category=0.77). Almost 70% of those who participated in the pilot study believed that impact analysis represented an improvement in how signals were prioritised. Impact analysis is a repeatable method of signal prioritisation that tended to give a higher level of priority to signals than the standard approach and which had an influence on the ultimate outcome.


Flowers prepare thyselves: leaf and root herbivores induce specific changes in floral phytochemistry with consequences for plant interactions with florivores.
The phenotypic plasticity of flowering plants in response to herbivore damage to vegetative tissues can affect plant interactions with flower-feeding organisms. Such induced systemic responses are probably regulated by defence-related phytohormones that signal flowers to alter secondary chemistry that affects resistance to florivores. Current knowledge on the effects of damage to vegetative tissues on plant interactions with florivores and the underlying mechanisms is limited. We compared the preference and performance of two florivores on flowering Brassica nigra plants damaged by one of three herbivores feeding from roots or leaves. To investigate the underlying mechanisms, we quantified expression patterns of marker genes for defence-related phytohormonal pathways, and concentrations of phytohormones and glucosinolates in buds and flowers. Florivores displayed contrasting preferences for plants damaged by herbivores feeding on roots and leaves. Chewing florivores performed better on plants damaged by folivores, but worse on plants damaged by the root herbivore. Chewing root and foliar herbivory led to specific induced changes in the phytohormone profile of buds and flowers. This resulted in increased glucosinolate concentrations for leaf-damaged plants, and decreased glucosinolate concentrations for root-damaged plants. The outcome of herbivore-herbivore interactions spanning from vegetative tissues to floral tissues is unique for the inducing root/leaf herbivore and receiving florivore combination.


Assessment of pain during medical procedures: a comparison of three scales.
Pain assessment is crucial to pain research. Knowledge about the strengths and weaknesses of pain measures is important to the continued advancement of our understanding of pain. The purpose of the present study was to compare the validity and utility of three measures of pain intensity during a medical procedure known to produce pain: an abortion. Assignment to one of three pain intensity assessment instruments, which were subsequently used to assess pain during an abortion procedure. Comparison of the relative sensitivity of the measures to assess changes in pain using a series of repeated measures analyses of variance. The relative utility of the measures was compared by examining the rates of accurate responses to each. Fifty-eight women presenting for a first-trimester abortion. Visual analog scale (VAS), the verbal 11-point Box Scale (Verbal BS-11), and the 21-point Box Scale (BS-21). All three pain intensity measures detected changes in pain during the abortion procedure. Rates of incorrect responses were higher for the Verbal BS-11 and the VAS than for the BS-21. The results supported the validity of each of the three measures used, although some superiority for the BS-21 over the Verbal BS- 11 and VAS exists. Patients had some difficulty completing the paper-and-pencil VAS during the procedure. In addition and consistent with previous research, some patients treated the Verbal BS-11 as a 21-point scale by responding with numbers between two whole numbers on the 0-10 measure. Overall, practical issues led us to conclude that the BS-21 is an excellent choice for assessing real-time abortion pain.


Carbohydrates as antigenic determinants of tumor-associated antigens recognized by monoclonal anti-tumor antibodies produced in a syngeneic system.
Two monoclonal antibodies (KH-1 and KH-2) against a transplanted fibrosarcoma (KMT-17) in WKA rats were produced by fusing a mouse myeloma (P3-X63-Ag8.653) with spleen cells from syngeneic rats hyperimmunized with KMT-17. Both antibodies showed complement-dependent cytotoxicity against KMT-17. By absorption of cytotoxicity, KH-1 reacted with homologous tumor, other syngeneic fibrosarcomas (KMT-80 and KMT-75), and lung and kidney from normal rats. However, KH-2 reacted with many kinds of tumors and various normal tissues. Antigen specificity was tested by complement fixation and/or solid-phase radioimmunoassay using glycolipids isolated from KMT-17 cells and authentic glycolipids. KH-1 reacted with globotriglycosyl ceramide which was not detected on KMT-17 cells and in cross-reacted weakly with IV3-alpha-galactosyl-lactoneotetraglycosyl ceramide, one of the major glycolipids of KMT-17. The immune reaction was inhibited by alpha-methyl-galactose. KH-2 reacted with lactosyl ceramide and lactoneotetraglycosyl ceramide. The reaction was more potently inhibited by lactose than by beta-methyl-galactose. Antibodies with similar specificity to either KH-1 or KH-2 were elevated in syngeneic rat sera after serial immunization with viable KMT-17 cells.


Biosensors for prostate cancer detection.
Prostate cancer (PC) is one of the most common tumors and a leading cause of mortality among men, resulting in ~375 000 deaths annually worldwide. Various analytical methods have been designed for quantitative and rapid detection of PC biomarkers. Electrochemical (EC), optical, and magnetic biosensors have been developed to detect tumor biomarkers in clinical and point-of-care (POC) settings. Although POC biosensors have shown potential for detection of PC biomarkers, some limitations, such as the sample preparation, should be considered. To tackle such shortcomings, new technologies have been utilized for development of more practical biosensors. Here, biosensing platforms for the detection of PC biomarkers such as immunosensors, aptasensors, genosensors, paper-based devices, microfluidic systems, and multiplex high-throughput platforms, are discussed.


Customized composite veneers from a totally digital workflow: A case report.
A treatment plan based on the use of a preview software can offer the possibility to rapidly communicate with the patient. Fully digital workflow allows for making several objects at the same time in a precise and cost-efficient manner.


Enhanced film-forming properties for ethyl cellulose and starch acetate using n-alkenyl succinic anhydrides as novel plasticizers.
The aim of this study was to investigate the ability of n-alkenyl succinic anhydrides (n-ASAs) to improve the film-forming characteristics of a novel coating polymer, potato starch acetate degree of substitution 2.8 (SA). n-ASAs were also applied to improve the otherwise brittle properties of ethyl cellulose (EC) aqueous dispersion (Aquacoat) and EC solvent-based films. The effectiveness of two n-ASAs, 2-octenyl succinic anhydride (OSA) and 2-dodecen-1-ylsuccinic anhydride were evaluated as plasticizers. Mechanical properties, both water vapor and drug permeabilities, and glass transition temperatures of the cast free films were measured. Triethyl citrate and dibutyl sebacate were used as reference plasticizers. The long hydrocarbon chain of n-ASA, with its accessible carbonyl groups, enabled a strong plasticization effect on the tested polymers. Due to the excellent mechanical properties (i.e., a tough film structure with considerable flexibility) and low permeability of the plasticized films, n-ASAs, and especially OSA proved to be an ideal plasticizer particularly for EC based coatings. Also, the EC aqueous dispersion plasticized with n-ASAs resulted in a markedly enhanced coalescence of the colloidal polymer particles, even at low drying temperatures. In applications where a coating with high flexibility is required, n-ASAs can be used as plasticizers at moderately high concentrations (up to 60-70%, w/w) without losing the high tensile strength, excellent toughness and low permeability of EC and SA films.


Exploration of labeling by near infrared dyes of the polyproline linker for bivalent-type CXCR4 ligands.
We have previously used poly-L-proline linkers for the development of bivalent-type ligands for the chemokine receptor, CXCR4. The bivalent ligands with optimum linkers showed specific binding to CXCR4, suggesting the existence of CXCR4 possibly as a dimer on the cell membrane, and enabled definition of the amount of CXCR4 expressed. This paper reports the synthesis by a copper-catalyzed azide-alkyne cycloaddition reaction as the key reaction, of bivalent CXCR4 ligands with near infrared (NIR) dyes at the terminus or the center of the poly-L-proline linker. Some of the NIR-labeled ligands, which would be valuable probes useful in studies of the behavior of cells expressing CXCR4, have been obtained. The information concerning the effects of the labeling positions of NIR dyes on their binding properties is useful for the design of modified bivalent-type CXCR4 ligands.


Investigating the effect of mono- and multivalent counterions on the conformation of poly(styrenesulfonic acid) by nanopores.
Polyelectrolytes are useful materials that have many technical, medical, physiological and biological applications. The properties of polyelectrolytes are determined not only by their chemical composition but also by their conformational states. However, the conformations of polyelectrolytes in solution are very difficult to characterize. Herein, we propose to use a protein nanopore to investigate the effect of mono- and multivalent counterions on the conformational changes of a simple polyelectrolyte, sodium poly(styrenesulfonic acid) (NaPSS). High concentration of KCl induced a conformational transition of NaPSS from "swollen random coil" form in low salt concentration to "random coil" form and was evidenced by the changes of the translocation event pattern. Addition of Mg2+ in buffer solution did not cause notable changes of NaPSS translocation events, but Dy3+ and Y3+ were shown to have remarkable effects on the translocation profile of NaPSS. Bridging events caused by Dy3+ or Y3+ between polyelectrolyte chains largely affected current blockage and dwell time of the translocation events. Our results provide experimental evidence for the classical theories of conformational transitions of polyelectrolytes and may find applications in many other polyelectrolyte-related researches.


Long-term survival and cure fraction estimates for childhood cancer in Europe (EUROCARE-6): results from a population-based study.
The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer. In this population-based study, we analysed 135 847 children (aged 0-14 years) diagnosed during 2000-13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival. 5-year survival for all childhood cancer combined in Europe in 2010-14 was 81% (95% CI 81-82), showing an increase of three percentage points compared with 2004-06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60-79] to 87% [77-93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010-13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73-75) in 1998-2001 to 80% (79-81) in 2010-13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74-100) for retinoblastoma to 60% (58-63) for CNS tumours and reached 90% (95% CI 87-93) for lymphoid leukaemia and 70% (67-73) for acute myeloid leukaemia. Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care. European Commission.


The teaching of crystallography: a historical survey.
The views of several well known crystallographers on how to teach the subject are presented with a description of teaching texts and schools available on a world-wide scale.


Early Alcohol and Smoking Initiation: A Contributor to Sexual Minority Disparities in Adult Use.
Lesbian, gay, and bisexual adults report higher rates of smoking and alcohol use than heterosexual peers. Prior studies have not examined whether potential disparities in early initiation among lesbian, gay, and bisexual youth may contribute to adult disparities. Data on 126,463 adults (including 8,241 lesbian, gay, and bisexual adults) were from the 2015-2017 National Survey on Drug Use and Health. Rates of reported early alcohol and smoking initiation (before age 15 years) among both lesbian/gay and bisexual adults were examined relative to same-gender heterosexual adults. Mediation analyses were used to assess whether early initiation differences contribute to disparities in adult heavy episodic drinking, alcohol use disorder, current smoking, and nicotine dependence for each subgroup. Analyses were conducted in 2018-2019. For both lesbian/gay and bisexual women, early alcohol initiation rates were elevated and explained 21%-38% of their observed disparities in adult heavy episodic drinking and alcohol use disorder. Similarly, early smoking initiation rates were elevated among both lesbian/gay and bisexual women and explained 22%-29% of their disparities in adult smoking and nicotine dependence. By contrast, no evidence was observed that early initiation mediated adult disparities for gay or bisexual men. A significant proportion of alcohol and smoking disparities among lesbian/gay and bisexual women in adulthood appear attributable to early initiation, indicating the need for enhanced early prevention efforts for these groups. Making routine adolescent screening for substance use, brief intervention, and referral to treatment more culturally sensitive to lesbian, gay, and bisexual youth may also be an important step in reducing adult disparities for lesbian, gay, and bisexual women.


Benign chondroblastoma of talus demonstrated by skeletal scanning.
A patient with a benign condroblastoma of the talus bone is described. A review of the pathogenesis and more common sites of predilection of this unusual tumor is presented. This is the first case, to our knowlege, shown by labeled phosphate scanning.


A reference center study in thyrotropin-secreting pituitary adenomas: clinicopathological, therapeutic and long-term follow-up outcomes.
This study aims to analyze the clinicopathological features, diagnostic steps, and therapeutic results of TSHomas and to reveal the effective factors on remission. The clinical, radiological, and pathological features and surgical and endocrinological results of 41 TSHoma cases followed between 2005 and 2022 were retrospectively analyzed. The factors affecting the surgical cure were investigated by comparing the groups with and without remission. A total of 41 patients (23 male,18 female) were included in the study and the mean age was 42 (31.5-49). Palpitation and headache were the most common complaints. The time from the onset of symptoms to diagnosis was 8 (3-20) months. There were 8 patients with a preoperative clinical and biochemical diagnosis of TSH + GH co-secretion. In the TRH stimulation test, a blunted TSH response was obtained in 18 patients (90.0%). Complete suppression could not be obtained in any of the patients who underwent the T3 suppression test. The median maximum tumor diameter was 19.0 mm (6.8-41). There was microadenoma in 4 (9.8%) patients and macroadenoma in 37 patients (92.8%). Remission was achieved in 31 (75.6%) of 40 patients who underwent endoscopic transsphenoidal surgery (eTSS). The Ki-67 labeling index was 2% (1.00-4.00) in the entire patient group. Preoperative use of antithyroid drugs appears to be significantly associated with surgical cure. Diagnosis of TSHoma is still full of challenges and dynamic tests remain important. Recognition and good management of inappropriate TSH secretion states affect subsequent surgical outcomes.


Ischemia-induced cleavage of OPA1 at S1 site aggravates mitochondrial fragmentation and reperfusion injury in neurons.
Neuronal mitochondrial dynamics are disturbed after ischemic stroke. Optic atrophy 1 (OPA1) and its GTPase activity are involved in maintaining mitochondrial cristae and inner membrane fusion. This study aimed to explore the role of OMA1-mediated OPA1 cleavage (S1-OPA1) in neurons exposed to cerebral ischemia and reperfusion. After oxygen-glucose deprivation (OGD) for 60 min, we found that mitochondrial fragmentation occurred successively in the axon and soma of neurons, accompanied by an increase in S1-OPA1. In addition, S1-OPA1 overexpression significantly aggravated mitochondrial damage in neurons exposed to OGD for 60 min and 24 h after OGD/R, characterized by mitochondrial fragmentation, decreased mitochondrial membrane potential, mitochondrial cristae ultrastructural damage, increased superoxide production, decreased ATP production and increased mitochondrial apoptosis, which was inhibited by the lysine 301 to alanine mutation (K301A). Furthermore, we performed neuron-specific overexpression of S1-OPA1 in the cerebral cortex around ischemia of middle cerebral artery occlusion/reperfusion (MCAO/R) mice. The results further demonstrated in vivo that S1-OPA1 exacerbated neuronal mitochondrial ultrastructural destruction and injury induced by cerebral ischemia-reperfusion, while S1-OPA1-K301 overexpression had no effect. In conclusion, ischemia induced neuronal OMA1-mediated cleavage of OPA1 at the S1 site. S1-OPA1 aggravated neuronal mitochondrial fragmentation and damage in a GTPase-dependent manner, and participated in neuronal ischemia-reperfusion injury.


Bowel Perforation in Vascular Ehlers-Danlos Syndrome: Case Report and Comprehensive Review.
Ehlers-Danlos syndromes (EDS) comprise a rare variety of genetic disorders, affecting all types of collagen. Herein, we describe a case of the vascular type of EDS, with coexisting segmental absence of intestinal musculature, while simultaneously performing a narrative review of the existing literature. A 23-year-old male patient with a history of multiple abdominal operations due to recurrent bowel perforations and the presence of a high-output enterocutaneous fistula was admitted to our surgical department for further evaluation and treatment. After detailed diagnostic testing, the diagnosis of vascular-type EDS (vEDS) was made and a conservative therapeutic approach was adopted. In addition, a comprehensive review of the international literature was carried out by applying the appropriate search terms. The diagnosis of vEDS was molecularly confirmed by means of genetic testing. The patient was treated conservatively, with parenteral nutrition and supportive methods. Thirty-four cases of bowel perforation in vEDS have been reported so far. Interestingly, this case is the second one ever to report co-existence of vEDS with Segmental Absence of Intestinal Musculature. Establishing the diagnosis of vEDS promptly is of vital significance in order to ensure that patients receive appropriate treatment. Due to initial non-specific clinical presentation, EDS should always be included in the differential diagnoses of young patients with unexplained perforations of the gastrointestinal tract.


Simultaneous two-dimensional HPLC determination of free D-serine and D-alanine in the brain and periphery of mutant rats lacking D-amino-acid oxidase.
A fully automated two-dimensional HPLC system combining a microbore-ODS column and a narrowbore-enantioselective column was designed and validated, and the amounts of D-serine (D-Ser) and D-alanine (D-Ala) in various tissues and physiological fluids of Long-Evans agouti/SENDAI (LEA/Sen) rats lacking D-amino-acid oxidase (DAO) were determined. Intra- and inter-day precision was less than 4.3% and accuracy ranged between 99.9 and 104%. LEA/Sen rats were reported to lack DAO in their kidneys and expected to be a novel mutant animal lacking DAO, however, the amounts of D-amino acids in the LEA/Sen rats have not been investigated. In the present study, the intrinsic amounts of D-Ser and D-Ala, which are neuromodulators of the N-methyl-D-aspartate (NMDA) receptors, were determined in seven brain tissues, four peripheral tissues, plasma and urine of the LEA/Sen rats and compared to those of the control (Wistar and SD) rats having normal DAO activity. The levels of D-Ser in the tissues and physiological fluids of the LEA/Sen rats were significantly higher than those of the Wistar and SD rats except for the frontal brain regions. Concerning D-Ala, the amounts in the tissues and physiological fluids of the LEA/Sen rats were drastically increased compared to those of the Wistar and SD rats. These results indicate that the intrinsic amounts of D-Ser and D-Ala in the tissues of rats are regulated by DAO, and that LEA/Sen rats would be useful for the study of NMDA receptor-related diseases in which DAO is implicated.


Quenching of the intrinsic fluorescence of bovine serum albumin by phenylfluorone-Mo(VI) complex as a probe.
In this paper, the binding characteristics of bovine serum albumin (BSA) and phenylfluorone (PF)-molybdenum (Mo(VI)) complex have been studied by fluorophotometry. The binding constants are calculated at different temperatures. The binding distance and the energy transfer efficiency between PF-Mo(VI) complex and protein are obtained on the basis of the theory of Forster energy transfer. DeltaH and DeltaS are calculated to be -7.11 kJ mol-1 and 70.30 J mol-1 K-1, which indicate that electrostatic force plays major role in the interaction of PF-Mo(VI) complex and BSA. The experimental results show that BSA and PF-Mo(VI) complex have strong interactions and the mechanism of quenching belongs to static quenching.


The future of CPD for general practitioners, registered pharmacy staff and general practice nurses in Scotland - qualitative responses from a national survey.
In the United Kingdom, undertaking continuing professional development (CPD) is required for revalidation with regulatory authorities for general practitioners, general practice nurses and registered pharmacy staff - pharmacists and pharmacy technicians. A survey of CPD preferences and activities of these four professions has been published and this paper focuses on one qualitative question in the survey: 'Please describe any changes that you anticipate in the way in which you will undertake CPD over the next 12 months.' Responses were analysed using content analysis, then codes and themes were developed into a coding framework. 1,159 respondents provided comments to the question and five themes were identified: options for learning, time, appraisal and revalidation, people in transition and use of technology. There was a desire for face-to-face courses, for interactive learning and for variety of learning methods. Respondents valued learning with others and Practice-Based Small Group Learning was considered to be flexible and promoted inter-professional learning and socialisation. Lack of time for learning was seen as a barrier for respondents. Respondents considered that CPD was needed to support them as their roles developed in primary healthcare.


Co-exposure of metals and high fat diet causes aging like neuropathological changes in non-aged mice brain.
In recent decades, humans' exposure to metals have increased due to industrialization and socioeconomic trends have caused increased high fat diet (HFD) consumption. Concurrently, metals and HFD are risk factors for health, and in particular, the cognitive impairment. The aim of this study was to evaluate the effect of metals and HFD treatment on neuropathological changes in young mice brain, and compare with untreated young mice (8-11 weeks = 2-3 months) and aged mice (12 months). Mice were given 300 ppm of Aluminum (Al), Copper (Cu), Lead (Pb) and Cadmium (Cd) in drinking water and HFD feed (40% of the feed weight was animal fat) for 42 days. Metals+HFD treated mice were subjected to behavior tests, such as, Morris water maze, elevated plus maze, fear condition and contextual memory to evaluate memory levels. Spatial memory (p < 0.01), contextual memory (p < 0.01) and fear memory (p < 0.05) were significantly impaired in metals+HFD group compared to young mice. The extent of neurodegeneration with metals+HFD co-exposure was considerably high in hippocampus (p < 0.01) and cortex (p < 0.01), compared to aged mice brain and untreated young mice. Increased oxidative stress was recorded in the cortex, hippocampus and amygdala of metals+HFD group compared to the young (p < 0.001) and aged group (p < 0.05). The acetylcholine concentration decreased in cortex, hippocampus and amygdala of metals+HFD group, explaining the cholinergic deficits that caused cognitive impairment. Among the studied metals, Al was found to be highly accumulated in cortex (p < 0.01), hippocampus (p < 0.01) and amygdala (p < 0.01); followed by Pb, Cu and Cd. Hippocampus showed greater accumulation of metals than the cortex and amygdala. This data provided the novel evidences that combined administration of metals and HFD enhanced aging process, caused memory impairment, cholinergic hypofunction, elevated oxidative stress and neurodegeneration in young mice.


A novel approach to seizures in neonates.
Recognition of seizures in neonates remains the foremost challenge to overcome. All neonates at risk for seizures, especially the critically ill, should undergo video-EEG monitoring. The initial step toward an accurate diagnosis is the accurate description and interpretation of the electro-clinical phenotype. THE IMPORTANCE OF SEIZURE SEMIOLOGY AND ASSOCIATION WITH ETIOLOGY: The early distinction between acute provoked seizures and neonatal-onset epilepsies serves as the primary determinant for guiding management, treatment choices, and duration. Seizures in neonates should be seen as a symptom, not a disease, and their semiology may suggest the etiology. Neonates with hypoxic-ischemic encephalopathy respond best to phenobarbital, while levetiracetam is a better choice for neonates with congenital heart diseases. Anti-seizure medication can be discontinued after 72 h of seizure freedom, before discharge from the hospital. Neonates with epilepsy usually require a personalized, etiology-based approach in terms of choice and duration of treatment. Neonates with channelopathies tend to respond to sodium channel blockers such as carbamazepine, oxcarbazepine, or phenytoin. The surgical option should be considered early in cases of large brain malformations, such as hemimegalencephaly.


New host material for high-performance blue phosphorescent organic electroluminescent devices.
A new carbazole derivative with two carbazole moieties on the C3 and C6 positions of carbazole and triphenylsilane directly linked to the N of carbazole is successfully used as a highly efficient blue phosphorescent host in an organic light-emitting diode (PhOLED). The blue PhOLED, with this new host, gives an extremely high external quantum efficiency.


Hemocytes and hemocytopoiesis in Silkworms.
A brief review is presented of the current state of ultrastructure, cytochemistry, and physiology of the hemocytes and meso- and metathoracic peri-imaginal-wing organs in silkworms. According to the accepted morphological classification, five circulating types of hemocytes are recognized in Bombyx mori as well as in Antheraea pernyi. They are prophemocytes or stem cells, plasmatocytes or pre-differentiated cells and three specialized cells, granulocytes, spherule cells and oenocytoids. During post-embryonic development the last four types are the most common in the circulating hemolymph. Plasmatocytes are considered to be pluripotent cells from which granulocytes, spherule cells and oenocytoids are derived. Contrary to the situation in most insects the plasmatocytes are not phagocytic in Antheraea. The granulocytes are efficient phagocytes. Both plasmatocytes and granulocytes are involved in pinocytosis. Another possible function of the granulocytes is hemolymph coagulation. The function of the spherule cells which contain a paracrystalline material (muco- or glycoproteins) is by no means clear. The phenoloxidase activity found within the cytosol of oenocytoids appears effective against the natural monophenol and diphenol substrates. The involvement of oenocytoids in the complex metabolism of phenols and particularly in the production of plasma phenolases has been reported. The mitotic division of five circulating hemocyte types is well known and was long regarded as the only mechanism of postembryonic hemocyte production. We present for silkworms, experimental evidence of the hemocytopoietic function of the meso- and metathoracic organs surrounding the imaginal wing discs. Ablation experiments demonstrate that the mitotic activity of free hemocytes is unable to maintain the normal hemocytogram in the absence of the two paris of organs. These organs are typically divided into cell islets ensheathed by a connective tissue membrane. Two types of islets may be classified by the disposition of the cells : the compact islets or aggregations of stem cells and the reticulate islets which are mainly composed of hemocytes at different steps of differentiation. The relative number of prohemocytes in the total hemocyte population ranges from 84 to 97 p. cent in organs of Antheraea pernyi. This well-defined cell type appears to be the major hemocyte type in hemocytopoietic organs. In Antheraea, the mitotic index (the relative number of mitotic hemocytes in the total cell population) varies from 0.5 to about 3 p. cent. Finally, our data direct attention to cyclic functional changes such as mitotic divisions and hemocyte differentiation which run parallel to the molting cycle.


Retraction Note: Chronic neuroinflammation and cognitive impairment following transient global cerebral ischemia: role of fractalkine/CX3CR1 signaling.
This article [1] has been retracted by the Editors-in-Chief. Based on the report of an inquiry conducted by Wayne State University and additional analysis conducted by the Office of Research Integrity (ORI) [2], the ORI informed the journal that the first author Dr Teresita L. Briones engaged in research misconduct by falsifying and/or fabricating data by falsely reporting the results of Western blot experiments, and that data reported in Figures 2A and 2C in [1] were duplicated, reused and falsely relabelled, and claimed to represent different experiments. We have not been able to contact any of the authors.


Biological membranes are rich in low-frequency motion.
Using 13C cross-polarization NMR techniques, we have found that the effect of protein on the dynamics of the hydrocarbon interior of a series of biological membranes is to depress the intensity of motion on the nanosecond timescale (i.e., T1 becomes longer) and to enhance the intensity of motion on the timescale of tens of microseconds (i.e., T1p becomes shorter.)


[The induction of neuronal differentiation in the glial fibrillary acid protein positive human neural progenitor cell line].
To investigate the ability of human GFAP positive neural progenitor cell line from the subventricular zone (SVZ) to differentiate into neurons. Real-time RT-PCR, Western blot analysis and immunocytochemistry were used to examine the expression level of the neural stem cell marker and neuronal-specific marker before and after all-trans-retinoic acid (AT-RA) induction in the GFAP positive neural progenitor cell line. Immunocytochemistry was used to examine the expression of the neuronal-specific marker after transplantation the GFAP positive neural progenitor cell line into the animal model. After induction, in the GFAP positive neural progenitor cell line the expression levels of the neuronal-specific marker increased, while the neural stem cell marker decreased both in mRNA and protein levels. After transplantation into animal model, the GFAP positive neural progenitor cell line could differentiate into neurons. The GFAP positive neural progenitor cell line could be induced to differentiate into neurons both in vitro and in vivo.


A 6-month observational study of the relationship between weight loss and behavioral symptoms in institutionalized Alzheimer's disease subjects.
Weight loss is a common occurrence in Alzheimer's disease (AD). This study was undertaken to investigate the relationship between weight loss and behavioral symptoms in institutionalized AD subjects. Observational study. Two facilities that included assisted living and nursing care. Residents with probable or possible AD (n = 32). Weight was measured monthly. At baseline, month 3, and month 6, a knowledgeable staff member provided information that included the Neuropsychiatric Inventory: Nursing Home Version (NPI-NH, ie, a measure of behavioral symptoms) and a questionnaire regarding eating habits, food intake, and appetite. Two-day calorie counts were done and accelerometers were worn to monitor physical activity. At baseline, the mean body mass index (BMI) was 24.0 (standard deviation, 3.5) with 12 subjects exhibiting a BMI <22. BMI was negatively associated with the baseline NPI-NH total score (Spearman Correlation Coefficient -0.52, P <0.01), which indicates that subjects with low BMIs were more likely to have higher frequency and severity of behavioral problems. Individual behavior scores for agitation/aggression (-0.40, P <0.05), depression (-0.31, P = 0.08), irritability/lability (-0.47, P <0.01), aberrant motor behavior (ie, pacing, -0.42, P <0.05), nighttime behavior (-0.37, P = 0.05), and appetite/eating (-0.48, P <0.01) at baseline were negatively correlated with baseline BMI. Behaviors not correlated with BMI were delusions, hallucinations, elation, apathy, and disinhibition. Although this was a small sample followed for a relatively short time period, change in specific NPI-NH scores from baseline to month 6 were correlated with the change in weight over the 6-month period. Both agitation/aggression (-0.37, P = 0.05) and disinhibition (-0.45, P <0.05) showed negative correlation with weight change, which indicates an association between changes in these behaviors and weight loss. There were no significant differences between those who lost weight (n = 13) and those who did not (n = 19) on baseline variables, which included age, comorbidity, functional status, and NPI-NH. However, those who lost weight had a significantly higher BMI at baseline than those who gained weight. These preliminary results suggest that behavioral disturbances play a role in low body weight and weight loss in AD subjects.


Experiences with the tracheoesophageal shunt method for vocal rehabilitation after total laryngectomy.
The tracheoesophageal (T-E) shunt technique reported by Komorn et al. (1973) was used for vocal rehabilitation in 8 laryngectomized patients including one case of hypopharyngeal cancer. It was proved that this technique was a simple one-stage procedure with a low incidence of complication. Four out of 7 patients, excluding one patient who died of another disease, acquired excellent speech without symptomatic aspiration. Two patients developed fairly good speech. One shunt was closed by aspiration. The shunt constructed by a flap measuring 2 x 4 cm, opened 1 cm below the distal end of the trachea, showed good results. The T-E shunt speech exceeds esophageal speech in duration and intelligibility.


Clinical and molecular characteristics of two Italian kindreds with hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome.
Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome, also known as Barakat syndrome, is a rare autosomal dominant disease characterized by the triad of hypoparathyroidism, deafness, and renal abnormalities. The disorder is caused by the haploinsufficiency of the zinc finger transcription factor GATA3 and exhibits a great clinical variability with an age-dependent penetrance of each feature. We report two unrelated kindreds whose probands were referred to our outpatient clinic for further evaluation of hypoparathyroidism. The proband of family 1, a 17-year-old boy, was referred for severe hypocalcemia (5.9 mg/dL) incidentally detected at routine blood tests. Abdomen ultrasound showed bilateral renal cysts. The audiometric evaluation revealed the presence of bilateral moderate hearing loss although the patient could communicate without any problem. Conversely, the proband of family 2, a 19-year-old man, had severe symptomatic hypocalcemia complicated by epileptic seizure at the age of 14 years; his past medical history was remarkable for right nephrectomy at the age of 4 months due to multicystic renal disease and bilateral hearing loss diagnosed at the age of 18 years. Based on clinical, biochemical, and radiologic data, HDR syndrome was suspected and genetic analysis of the GATA3 gene revealed the presence of two pathogenetic variants in exon 3, c.404dupC and c.431dupG, in the proband of family 1 and 2, respectively. HDR syndrome is a rare cause of hypoparathyroidism and must be excluded in all patients with apparently idiopathic hypoparathyroidism. A correct diagnosis is of great importance for early detection of other HDR-related features and genetic counseling.


Bioconcentration factors and trace elements bioaccumulation in sporocarps of fungi collected from quartzite acidic soils.
The content of 19 metals (Al, V, Cr, Co, Ni, Cu, Zn, Ga, Rb, Sr, Zr, Nb, Cs, Ba, Ce, Pb, Th, U and Nd) was investigated in 15 edible species of phylum Basidiomycota collected in an area with quartzite acidic soils in a province of the central Spain. The study explores the differences in metal accumulation in relation to fungal species, and the results were related to metal content in soil through the determination of bioconcentration factors. Regarding the highest concentrations, Zn, Al, Cu and Rb were the metals more accumulated in the sporocarps. Notable concentrations were also found in Sr, Zr, Ba, Cs and Ce. The major bioconcentration factors were found for Cu and Zn in sporocarps of Agaricus silvicola and Lepista nuda. Regarding the different species, Tricholoma equestre and Cantharellus cibarius were those with the greatest capacity to absorb trace elements, and in contrast, Amanita caesarea and Agaricus campestris showed the lowest values. The cluster analysis shows that there are some species with the same nutritive physiology that share similarities in the absorptive behaviour. Lactarius sanguifluus and Lactarius deliciosus, both ectomycorrhizas of the genus Pinus, are closely related, and Clitocybe gibba, L. nuda and Marasmius oreades, all of them saprobes on soil organic matter, are very close too.


[Epidemiological aspects of the hospitalized patients with acute viral hepatitis (author's transl)].
The Authors propose epidemiological studies on 179 patients hospitalized for viral hepatitis in the Department of Medicine of Fiorenzuola D'Arda Hospital from 1966 to 1977. The Authors prove, besides, the worrying incidence of disease and locate two zones of different frequency of hepatitis in the considered territory; they advise any possible causes of thys; they put forward any proposals about the control of disease.


Urinary tract infections in childhood: the place of the nitrite test.
The effectiveness of the nitrite test available on the N-Multistix (Ames Co.) was compared with that of the microscopic examination of urine as a screening test for the detection of urinary tract infections in children presenting to a general paediatric clinic. The nitrite test gave a positive result in 59% of children with urinary infections, while microscopic pyuria (more than 50 white blood cells per cubic millimetre of uncentrifuged urine) was found in 72% of the same group. Of children who did not have a urinary tract infection, 2.8% had microscopic pyuria compared with only 0.2% who showed a false-positive nitrite test result. The ease and rapidity of the nitrite test make it a useful screening test for the presumptive diagnosis of urinary tract infections, and in certain circumstances it is preferable to the conventional microscopic examination of urine. However, as in the case of microscopic examination, urine culture must always be performed to avoid missing the urinary infections that are not detected by the screening test.


Nucleoside analogs: molecular mechanisms signaling cell death.
Nucleoside analogs are structurally similar antimetabolites that have a broad range of action and are clinically active in both solid tumors and hematological malignancies. Many of these agents are incorporated into DNA by polymerases during normal DNA synthesis, an action that blocks further extension of the nascent strand and causes stalling of replication forks. The molecular mechanisms that sense stalled replication forks activate cell cycle checkpoints and DNA repair processes, which may contribute to drug resistance. When replication forks are not stabilized by these molecules or when subsequent DNA repair processes are overwhelmed, apoptosis is initiated either by these same DNA damage sensors or by alternative mechanisms. Recently, strategies aimed at targeting DNA damage checkpoints or DNA repair processes have demonstrated effectiveness in sensitizing cells to nucleoside analogs, thus offering a means to elude drug resistance. In addition to their DNA synthesis-directed actions many nucleoside analogs trigger apoptosis by unique mechanisms, such as causing epigenetic modifications or by direct activation of the apoptosome. A review of the cellular and molecular responses to clinically relevant agents provides an understanding of the mechanisms that cause apoptosis and may provide rationale for the development of novel therapeutic strategies.


Variations in egg size of Trichuris trichiura.
In patients infected with Trichuris trichiura, large eggs as well as more typical eggs were frequently found in the feces; these large eggs have been attributed to human infection by T. vulpis. To clarify whether the female worms laying the large eggs were T. trichiura or T. vulpis, we examined the morphology of adult worms and the size of whipworm eggs obtained from a patient and from several domestic dogs. Adult female T. trichiura worms were easily and quickly distinguished from those of T. vulpis by their convoluted vaginal tracts and uteri. Eggs obtained from the uteri of T. trichiura were of two sizes, with approximately 80% being of the smaller variety (57 X 26 microns) and 20%, the larger (78 X 30 microns). These percentages were about equal to those found the feces of the patient. T. vulpis uterine eggs were slightly larger (82 X 39 microns) than the large eggs of T. trichiura. The distribution of the 2 populations of eggs in 30 adult female T. trichiura was as follows: 1 worm had only large eggs, 14 had only the typical smaller eggs, and 15 had both varieties in their uteri.


Difference of high-salinity-induced inhibition of ammonia-oxidising bacteria and nitrite-oxidising bacteria and its applications.
The difficulty in achieving stable partial nitritation (PN) is a challenge that limits the application of mainstream anaerobic ammonium oxidation (anammox). This study proposes high-salinity treatment as a novel strategy for inactivating nitrite-oxidising bacteria (NOB). The study indicated that NOB are more sensitive to high salinity than ammonia-oxidising bacteria (AOB). The inhibitory effect on the nitrifier gradually increased with increasing salinity from 0 to 100 g NaCl/L. After 24 h and 35 g NaCl/L inhibition, the AOB and NOB activities were 36.65% and 7.15% of their original activities, respectively. After one high-salinity treatment, nitrite accumulation rate (NAR) was above 33% during nitrification. Moreover, the sludge characteristics remained almost unchanged after suppression. A novel process for achieving mainstream PN was proposed and evaluated based on the results. An energy consumption analysis showed that mainstream PN/anammox based on the ex situ high-salinity treatment can achieve higher energy self-sufficiency compared with activated sludge.


Risks of applying mobilising agents for remediation of arsenic-contaminated soils: Effects of dithionite-EDTA and citric acid on arsenic fractionation, leachability, oral bioavailability/bioaccessibility and speciation.
Arsenic (As) mobilisation assists in remediating As-contaminated soils but might increase ecological and health risks. In this study, risks of applying two mobilising agents were assessed, i.e. an emerging reducing-chelating composite agent [dithionite (Na2S2O4)-EDTA] and a classical low-molecular-weight organic acid (LMWOA) [citric acid (C6H8O7)]. Results showed that both agents induced sharp increase in leachability-based ecological risk of As. Interestingly, the two agents had opposite performances regarding health risks. Na2S2O4-EDTA significantly increased As relative bioavailability (RBA) to 1.83 times that in controls based on in vivo mouse model, and As bioaccessibility to 1.96, 1.65 and 1.20 times in gastric, small intestinal and colon phases based on in vitro PBET-SHIME model. Besides, it caused significant increase of highly toxic As(Ⅲ) in colon fluid. In contrast, C6H8O7 significantly reduced RBA and bioaccessibility of soil As in colon by 44.44% and 14.65%, respectively. Importantly, C6H8O7 restrained bioaccessible As(V) reduction and promoted bioaccessible As(Ⅲ) methylation, further reducing health risk. The phenomena could mainly be attributed to excessive metal components release from soil by C6H8O7 and gut microbiota metabolism of C6H8O7. In summary, C6H8O7 and similar LMWOAs are recommended. The study contributes to mobilising agent selection and development and provides a reference for managing remediation sites.


Comparison of 5-aminolevulinic acid-encapsulated liposome versus ethosome for skin delivery for photodynamic therapy.
Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an alternative therapy for many non-melanoma skin cancers. The major limitation of this therapy, however, is the low permeability of ALA through the stratum corneum (SC) of the skin. The objective of the present work was to characterize ethosomes containing ALA and to enhance the skin production of protoporphyrin IX (PpIX), compared to traditional liposomes. Results showed that the average particle sizes of the ethosomes were less than those of liposomes. Moreover, the entrapment efficiency of ALA in the ethosome formulations was 8-66% depending on the surfactant added. The particle size of the ethosomes was still approximately <200 nm after 32 days of storage. An in vivo animal study observed the presence of PpIX in the skin by confocal laser scanning microscopy (CLSM). The results indicated that the penetration ability of ethosomes was greater than that of liposomes. The enhancements of all the formulations were ranging from 11- to 15-fold in contrast to that of control (ALA in an aqueous solution) in terms of PpIX intensity. In addition, colorimetry detected no erythema in the irradiated skin. The results demonstrated that the enhancement ratio of ethosome formulations did not significantly differ between the non-irradiated and irradiated groups except for PE/CH/SS, which may have been due to a photobleaching effect of the PDT-irradiation process.


Prolonged infusion of gemcitabine: clinical and pharmacodynamic studies during a phase I trial in relapsed acute myelogenous leukemia.
To determine the maximum tolerated duration of infusions at the fixed gemcitabine dose rate of 10 mg/m(2)/min and to analyze the pharmacodynamic actions in leukemia blasts during gemcitabine therapy. The study was conducted in a phase I trial by escalating the duration of gemcitabine infusion at a fixed-dose rate of 10 mg/m(2)/min. Patients with relapsed or refractory acute myelogenous leukemia (AML) received gemcitabine for 8.0 (n = 3), 10.0 (n = 3), 12.5 (n = 8), 15.5 (n = 3), or 18.0 hours (n = 2). Pharmacokinetic and pharmacodynamic investigations were undertaken in circulating AML blasts. Gemcitabine was infused for up to 18 hours at the fixed-dose rate. Four patients had grade 3 toxicities at longer infusion schedules. One patient had a partial remission; two others had a reduction in blasts and concomitant rise in neutrophils. Gemcitabine triphosphate was detectable in AML cells even at 1 hour after the start of infusion in eight patients. The concentration ranged from 130 to 900 micromol/L at the end of the infusion. Consistently, there was a rapid decline in DNA synthesis, which remained suppressed at 85% to 95% during and for at least 10 hours after the end of the infusion. Compared with levels in cells measured before therapy, at 8 hours after the start of the infusion, there was a decline in the cellular purine deoxynucleotide pools. At the fixed-dose rate of 10 mg/m(2)/min, gemcitabine could be administered for longer than 12 hours without untoward toxicity. The favorable toxicity profile and pharmacokinetic and pharmacodynamic features warrant combination with DNA-damaging agents.


Baseline natriuretic peptides as a predictor of atrial fibrillation recurrence after radiofrequency-based pulmonary vein isolation in a non-heart failure population: A subanalysis from DECAAF II.
Brain natriuretic peptide (BNP) is a marker of myocardial stretch and may have prognostic significance in patients with atrial fibrillation (AF) without heart failure (HF). We investigated the association between baseline BNP levels and arrhythmia recurrence following pulmonary vein isolation (PVI) among patients with persistent AF without HF. We analyzed 125 patients with persistent AF without HF who had baseline BNP measured from the DECAAF II trial. The primary outcome was arrhythmia recurrence following ablation. The baseline characteristics across the two groups were compared using Chi-square test and Wilcoxon rank test accordingly. Cox regression analysis was used to analyze the association between baseline BNP levels and the primary outcome. Across the entire cohort, 64 (51%) patients experienced arrhythmia recurrence. When comparing patients who experienced arrythmia recurrence to patients who did not, patients with recurrent arrhythmia had higher levels of pre-ablation BNP, as evidenced by differences in means (330.05 pg/mL) compared to patients without recurrent arrhythmia (182.39 pg/mL) (p < .05). A cut-off BNP value of 300 pg/mL provided the largest area under curve (AUC) of receiver-operating characteristic (ROC) curve on univariate logistic regression. On unadjusted Cox analysis, for every 100 unit increase in BNP, the hazard ratio for the primary outcome increased 1.09 (1.026-1.158) times (p = .004). After adjusting for sex, hypertension, and stroke, the results remained significant (HR = 1.8516, CI 95% [1.0139 - 3.381], p = .045). In the non-heart failure population, BNP levels predict AF recurrence following PVI in persistent AF patients.


Ultrastructural localization of adrenergic nerve terminals in the circular muscle layer and muscularis mucosae of the rat duodenum after acute treatment with 6-hydroxydopamine.
The ultrastructure of the intrinsic adrenergic innervation of the circular muscle coat and muscularis mucosae of rat duodenum has been studied following acute treatment with 6-hydroxydopamine. Adrenergic terminals were found among intramuscular nerve bundles. They were most numerous in the outer layer of the circular coat, where close neuromuscular contacts were commonly encountered. Adrenergic terminals also innervated the inner layer of the circular coat and the muscularis mucosae, where only wide neuromuscular contacts have been found. The evidence suggests that smooth muscle cells in the rat duodenum may be directly influenced by adrenergic nerves.


[Effects of electroacupuncture plus oxygenmedicine on the expression of Bcl-2 and Bax proteins in the hippocampal CA 1 area in rats with global cerebral ischemia/reperfusion injury].
To observe the effect of electroacupuncture (EA) plus oxygenmedicine (OM) on the expression of Bcl-2 and Bax in the hippocampal CA 1 area in cerebral ischemia/reperfusion injury (CI/RI) rats. Thirty SD rats were randomized into sham-operation, model, EA, OM, EA+OM groups (n=6 /group). CI/RI model was established by using modified Pulsinelli 4 vessel occlusion and reperfusion. EA (100 Hz, 3.5 mA) was applied to "Baihui" (GV 20) and "Zusanli" (ST 36) 30 min, once daily for 4 days. Rats of OM and EA+ OM groups were put into a box filled with oxygen and atomized herbal medicines containing Bingpian (Borneolum), Shexiang (Moschus), Huangjing (Rhizoma Polygonati), Shouwu (Radix Polygoni Multiflori), etc. for 30 min, once daily for 4 days. Bcl-2 and Bax expression of the hippocampal CA 1 area was detected by immunohistochemistry. Compared with sham group, the numbers of Bcl-2 immunoreaction (IR) and Bax IR positive cells, and the immunoactivity of Bcl-2 IR and Bax IR positive products in the hippocampal CA 1 area were increased significantly in model group (P < 0.05, P < 0.01). In comparison with model group, the number of Bcl-2 IR positive cells and Bcl-2 immunoactivity in EA, OM and EA+OM groups increased considerably (P < 0.01), while Bax IR positive cell numbers and Bax immunoactivity in EA, OM and OM+ EA groups decreased significantly (P < 0.01). The effects of EA+ OM were significantly superior to those of EA and OM groups in upregulating Bcl-2 IR positive cell number and Bcl-2 immunoactivity and downregulating Bax IR positive cell number and Bax immunoactivity (P < 0.01). No significant differences were found between EA and OM groups in the abovemen-EA and OM and EA+OM can effectively regulate the expression of Bcl-2 and Bax in tioned indexes (P > 0.05). EA and OM and EA + OM can effectively regulate the expression of Bcl-2 and Bax in the hippocampal CA 1 area in CI/RI rats, and the effects of EA+OM are significantly superior to those of simple EA and simple OM, which may contribute to their effect in improving cerebral ischemia.


Berberine inhibits gastric cancer development and progression by regulating the JAK2/STAT3 pathway and downregulating IL-6.
Gastric cancer is a prevalent malignant tumor that seriously affects human health. Berberine (BBR), an alkaloid from Chinese herbal medicines, inhibits the proliferation of various cancers. We evaluated the effects and related mechanisms of BBR on gastric cancer. The MTT assay, flow cytometry, scratch assays, transwell experiments and xenograft nude mice models were used to investigate the antineoplastic effects of BBR. RNA-Seq, qRT-PCR, WB and ELISA were used to investigate the underlying mechanisms of BBR on gastric cancer metastasis. BBR treatment inhibited the proliferation of MKN-45 and HGC-27 cells, induced their apoptosis, G0/G1 cell arrest, and suppressed the migration as well as invasion of GC cells in vitro. Moreover, BBR inhibited in vivo tumor growth in MKN-45 xenograft mice. RNA-seq showed that interactions between cytokines and their receptors was one of the greatest enrichment modulated pathways and IL-6 was a key target. IL-6 knockdown significantly inhibited the activities of MKN-45 cells. Mechanistically, these findings imply that BBR inhibits GC cell proliferation by modulating the signaling pathways related to IL-6/JAK2/STAT3. This study provides a theoretical basis for the use of BBR in gastric cancer prevention.