Patient Survival and Technique Failure in Continuous Ambulatory Peritoneal Dialysis Patients with Prior Stroke.
♦ To investigate patient survival and technical failure of patients with prior stroke receiving continuous ambulatory peritoneal dialysis (CAPD) in Southern China. ♦ This was a retrospective study. All subjects were recruited from the peritoneal dialysis center in The First Affiliated Hospital of Sun Yat-sen University from 1 January 2006 to 31 December 2010. All eligible patients were assigned to stroke group and non-stroke group according to a history of stroke before receiving CAPD. The primary outcomes were all-cause mortality and death-censored technical failure. Cox regression was used to estimate risk factors of all-cause mortality and death-censored technique failure. ♦ Of the 1,068 recruited patients, 75 (7.0%) patients had a previous history of stroke. The all-cause mortality and death-censored technique failure were significantly higher in the stroke group compared with the non-stroke group, respectively (odds ratio [OR] 2.67, 95% confidence interval [CI] 1.59 - 4.46 and OR 2.52, 95% CI 1.19 - 5.34). Older age (changed by 10 years, hazard ratio [HR] 1.90, 95% CI 1.07 - 3.38), lower body mass index (BMI 18.5 - 23.9 vs < 18.5 kg/m(2) reference, HR 0.17, 95% CI 0.05 - 0.55) and time to the first episode of peritonitis (HR 0.93, 95% CI 0.89 - 0.96) were independently associated with increased risk of all-cause mortality in patients with prior stroke. In addition, time to the first episode of peritonitis was associated with decreased risk of death-censored technique failure (HR 0.91, 95% CI 0.84 - 0.99) in those with prior stroke. ♦ Continuous ambulatory peritoneal dialysis patients with prior stroke had high rates of all-cause mortality and technique failure compared with those without prior stroke. Older age, lower BMI, and time to the first episode of peritonitis were independent risk factors of all-cause mortality in patients with prior stroke.


The effect of glial cell line-derived neurotrophic factor in fibrin glue on developing dopamine neurons.
Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta superfamily, promotes the survival, morphological differentiation, and high-affinity dopamine (DA) uptake of cultured nigral DA neurons. In order to test potential methodology for peptide delivery in vivo, GDNF-containing fibrin glue balls (8 micrograms/ball) were incorporated with pieces of fetal ventral mesencephalon (E15) and transplanted into the anterior chambers of sympathetically denervated adult rats. Five weeks after grafting, the numbers of TH-positive neurons and the nerve fiber density were significantly higher in the ventral mesencephalic grafts treated with GDNF-containing glue balls than in those treated with vehicle. In addition, the laminin and GFAP immunoreactivities were similar between the two groups. These data support the concept that GDNF is a potent trophic factor for DA neurons in vivo and suggest that fibrin glue may provide a unique and safe means to permit prolonged delivery of trophic molecules to CNS tissues.


Assessment of lead exposure in indoor shooters in central Poland.
A steady increase in shooting practices is observed worldwide. Potential lead exposure at shooting ranges poses a risk to their employees and users, which is not widely reported outside of the USA, especially in Poland. Exposure to lead results from the use of bullets containing lead and the main route of exposure to this metal at shooting ranges is inhalation, i.e., during shooting or cleaning. The aim of this study was to assess lead exposure of employees and users in selected indoor shooting ranges in central Poland. Airborne lead concentrations at all locations in the shooting ranges were above Polish occupational exposure limit (OEL, 0.05 mg m-3). Elevated blood and urine lead levels, and decreased 4-aminolevulinic acid dehydratase activity (ALA-D) were found in subjects participating in shooting even for only a few (< 10) hours per week. Lead exposure at shooting ranges in central Poland, as indicated by elevated blood lead levels and decreased ALA-D activity, could represent an elevated risk for adverse health effects. Thus, information on the possible health consequences of lead exposure should be provided at these sites, and biomonitoring appears to be reasonable for regular workers and shooters.


Effects of acute swim stress on LiCl-induced conditioned taste aversions.
The present study examined the effects of a 5-min period of swim stress experienced between a flavor (saccharin) and illness (LiCl) on conditioned taste aversion learning. Experiment 1 obtained a stress-induced attenuation of learning. Experiment 2 replicated the findings of Experiment 1, and also obtained a similar attenuation when stress was administered 30 min prior to the saccharin presentation. Experiment 3 examined the effects of swim stress either 15 min or 90 min after the LiCl had been administered. It was found that swim stress 15 min after LiCl significantly attenuated CTA, but swim stress 90 min after LiCl did not. These results are discussed with regard to current views of the relationship between external events and conditioned taste aversions.


A junctionless SONOS nonvolatile memory device constructed with in situ-doped polycrystalline silicon nanowires.
In this paper, a silicon-oxide-nitride-silicon nonvolatile memory constructed on an n+-poly-Si nanowire [NW] structure featuring a junctionless [JL] configuration is presented. The JL structure is fulfilled by employing only one in situ heavily phosphorous-doped poly-Si layer to simultaneously serve as source/drain regions and NW channels, thus greatly simplifying the manufacturing process and alleviating the requirement of precise control of the doping profile. Owing to the higher carrier concentration in the channel, the developed JL NW device exhibits significantly enhanced programming speed and larger memory window than its counterpart with conventional undoped-NW-channel. Moreover, it also displays acceptable erase and data retention properties. Hence, the desirable memory characteristics along with the much simplified fabrication process make the JL NW memory structure a promising candidate for future system-on-panel and three-dimensional ultrahigh density memory applications.


'Read for Nutrition' programme improves preschool children's liking and consumption of target vegetable.
To determine whether the 'Read for Nutrition' programme would increase liking and consumption of broccoli (a target vegetable) in preschool children and test acceptability and practicality of the programme. Pilot pre-post intervention study, where childcare teachers received training and coaching followed by reading the book 'Monsters Don't Eat Broccoli' multiple times with the children during a three-week intervention. Five classrooms of Educare, Lincoln, Nebraska in 2018. Sixty-nine (11 to 16 children per classroom) preschool-aged children and sixteen teachers (minimum, three per classroom). Average total consumption of broccoli increased 35 % (0·14 ounces or 0·05th cup) after the 'Read for Nutrition' programme (t = 2·66; P = 0·01; 95 % CIs (0·035, 0·246)) for all children. Proportional consumption increased for children who received ≥ five exposures to the book (t46 = 2·77; P = 0·008). Exposures to the book predicted proportional consumption (β = 0·365; P = 0·002). Liking of broccoli increased (W69 = 2·2, P = 0·03) as well. Teachers rated the programme as acceptable, practical and enjoyable to children and to themselves. Programmes such as 'Read for Nutrition' have the potential to improve children's vegetable liking and consumption in early care and education settings with only book readings and no exposure to a real vegetable.


Evidence for broken minocycline by NMR and HPLC techniques: a new additional resistance mechanism mediated by tetB determinant.
As demonstrated by microbiological assays, a decrease in the active minocycline level occurs in spent media from each Escherichia coli K12 recipient containing one of 10 different plasmids bearing tetB determinants. No such decrease was detected when tetA, C, D or E determinants were tested under the same conditions. Likewise, no decrease in tetracycline or doxycycline levels was detected when 20 plasmids bearing tetA to E determinants were tested. Studies carried out by nuclear magnetic resonance and high pressure liquid chromatography proved that minocycline is broken by a mechanism mediated by the tetB determinant. This new mechanism can be considered as additional to the active efflux of minocycline.


The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion.
A model of the energetics of lipid assemblies (Siegel. 1993. Biophys. J. 65:2124-2140) is used to predict the relative free energy of intermediates in the transitions between lamellar (Lalpha) inverted hexagonal (HII), and inverted cubic (QII) phases. The model was previously used to generate the modified stalk theory of membrane fusion. The modified stalk theory proposes that the lowest energy structures to form between apposed membranes are the stalk and the transmonolayer contact (TMC), respectively. The first steps in the Lalpha/HII and Lalpha/QII phase transitions are also intermembrane events: bilayers of the Lalpha phase must interact to form new topologies during these transitions. Hence the intermediates in these phase transitions should be similar to the intermediates in the modified stalk mechanism of fusion. The calculations here show that stalks and TMCs can mediate transitions between the Lalpha, QII, and HII phases. These predictions are supported by studies of the mechanism of these transitions via time-resolved cryoelectron microscopy (. Biophys. J. 66:402-414; Siegel and Epand. 1997. Biophys. J. 73:3089-3111), whereas the predictions of previously proposed transition mechanisms are not. The model also predicts that QII phases should be thermodynamically stable in all thermotropic lipid systems. The profound hysteresis in Lalpha/QII transitions in some phospholipid systems may be due to lipid composition-dependent effects other than differences in lipid spontaneous curvature. The relevant composition-dependent properties are the Gaussian curvature modulus and the membrane rupture tension, which could change the stability of TMCs. TMC stability also influences the rate of membrane fusion of apposed bilayers, so these two properties may also affect the fusion rate in model membrane and biomembrane systems. One way proteins catalyze membrane fusion may be by making local changes in these lipid properties. Finally, although the model identifies stalks and TMCs as the lowest energy intermembrane intermediates in fusion and lamellar/inverted phase transitions, the stalk and TMC energies calculated by the present model are still large. This suggests that there are deficiencies in the current model for intermediates or intermediate energies. The possible nature of these deficiencies is discussed.


[What prognostic factors correlate with activities of daily living (Barthel Index) 1 year after para-articular hip fracture? A prospective observational study].
The aim of this prospective study was to identify prognostic factors predicting post-operative outcome in patients one year after their hip fracture. From October 1996 until September 1997 all patients (n = 98) treated for a hip fracture in our hospital were prospectively included into the study. Follow up was performed at three, six and twelve months after the injury. The main outcome variable was the activity of daily living measured by the Barthel-Index. An univariate analysis of the variables age, gender, ASA-classification, type of fracture and treatment, length of stay and rehabilitation was performed and all these variables were correlated with the Barthel-Index. A multiple logistic regression was performed for identification of prognostic factors predicting outcome. The one year lethality was 33% (n = 31). All patients younger than 75 years reached their preoperative activity level at one year follow up. Patients with age of 75 years or more experienced a reduction of their activities of daily living of 20%. The ADL-differences of both groups at the follow up after 3, 6 and 12 months showed a significant p-value (p < 0.001). The ADL-differences between the group of patients with or without a transfer to a specialized rehabilitation center were not significant. The multivariate analysis showed that the preoperative use of the Barthel-Index was the best prognostic factor for outcome until one year after the injury. The preoperative Barthel-Index should be seriously considered for therapeutic decision making in patients with hip fractures.


Ligand western blotting for specific detection of active forms of proteases.
We developed a non-radioactive method of ligand western blotting for specific detection of active forms of serine proteases. The method consists of three steps: (i) separation of proteins by electrophoresis in sodium dodecyl sulfate-polyacrylamide gel, followed by blotting of proteins to nitrocellulose membrane; (ii) binding of a specific ligand, such as soybean trypsin inhibitor labeled with biotin, to protease on the membrane; and (iii) detection of the protease-inhibitor complex by color reaction (or chemiluminescence) developed by streptavidin-conjugated peroxidase (or alkaline phosphatase). By using this method, plasmin and trypsin (serine proteases) were detected, but papain (thiol protease) or pepsin (acidic protease) was not. Plasmin was detectable up to less than 4 ng. Inactive precursors of serine protease, i.e. plasminogen and trypsinogen, did not exhibit visible bands until they were activated by treatment with streptokinase or trypsin, respectively. We applied this method to clinical samples, and succeeded in detecting plasminogen, after conversion to plasmin with streptokinase treatment, in as little as 5 microliters of serum or trypsin, as it was in 10 microliters of pancreatic juice.


Is compromised intestinal barrier integrity responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia?
Compromised intestinal barrier integrity can be independently driven by hyperglycemia, and both hyperglycemia and intestinal barrier injury are associated with poor prognosis in critical illness. This study investigated the intestinal barrier biomarkers in critically ill patients, to explore the role of compromised intestinal barrier integrity on the prognosis of critically ill patients with pre-existing hyperglycemia. This was a retrospective observational study. The relationships between intestinal barrier biomarkers and glycated hemoglobin A1c (HbA1c), fasting blood glucose (FBG), indicators of clinical characteristics, disease severity, and prognosis in critically ill patients were investigated. Then the metrics mentioned above were compared between survivors and non-survivors, the risk factors of 90-day mortality were investigated by logistic regression analysis. Further, patients were divided into HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group, metrics mentioned above were compared between these two groups. A total of 109 patients with critical illness were included in the study. D-lactate and lipopolysaccharide (LPS) were associated with sequential organ failure assessment (SOFA) score and 90-day mortality. LPS was an independent risk factor of 90-day mortality. DAO, NEU (neutrophil) proportion, temperature, lactate were lower in HbA1c ≥ 6.5% Group while D-lactate, LPS, indicators of disease severity and prognosis showed no statistical difference between HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group. Intestinal barrier integrity is associated with the disease severity and prognosis in critical illness. Compromised intestinal barrier integrity might be responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia.


Effects of cholinergic drugs on learning impairment in ventral globus pallidus-lesioned rats.
The excitotoxin kainic acid (10 nmol/microliter) was used to produce bilateral lesions in the nucleus basalis magnocellularis (NBM) of rats which provides extensive cholinergic innervation to the cerebral cortex. The behavioral effects of physostigmine, THA (9-amino-1,2,3,4-tetrahydroacridine hydrochloride) and NIK-247 (9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrate hydrochloride) were investigated by observing locomotor activity, shock sensitivity and passive avoidance response in the NBM-lesioned rats. Evaluation of locomotor activity and shock sensitivity in the experimental animals did not reveal any sensorimotor disturbances caused by the lesions. Oral administration of 1 and 2 mg/kg physostigmine reduced the locomotor activity in the NBM-lesioned rats, while physostigmine (0.5 mg/kg), THA (1 or 3 mg/kg) and NIK-247 (1 or 3 mg/kg) had no effect on locomotor activity. Compared with the sham-operated controls, the NBM-lesioned rats exhibited a significantly lesser deficit in the retention of the passive avoidance response. THA (1 or 3 mg/kg) and NIK-247 (1 or 3 mg/kg) elicited good retention of the passive avoidance response. Rats with NBM lesions showed impaired acquisition of a passive avoidance response when trained repeatedly at 24-h intervals. Also, when post-training NBM lesions were induced, there was rapid extinction of the acquired passive avoidance response. THA or NIK-247 administered at doses of 3 mg/kg significantly increased response latencies of post-trained NBM-lesioned rats. THA or NIK-247 administered once a day in doses of 1 or 3 mg/kg p.o. produced a very significant increase of acetylcholine in the cerebral cortex of NBM-lesioned rats after the 21st administration. These finding suggest that THA and NIK-247 exert an ameliorating effect on memory disturbance induced by NBM lesions in rats.


The effects of temperature on the crystalline properties and resistant starch during storage of white bread.
Resistant starch (RS) can form during storage of foods, thereby bestowing a variety of potential health benefits. The purpose of the current study has been to determine the influence of storage temperature and time on the crystallinity and RS content of bread. Loaves of white bread were baked and stored at refrigeration, frozen and room temperatures with analysis over a period of zero to seven days. RS determination and X-ray diffraction (XRD) were used to evaluate the influence of storage temperature and time on total crystallinity and RS content. The rate of starch recrystallisation was affected by storage temperature and time, where refrigeration temperatures accelerated RS formation and total crystallinity more than storage time at both frozen and room temperature. A strong statistical model has been established between RS formation in bread and XRD patterns, having a 96.7% fit indicating the potential of XRD to measure RS concentrations.


Overexpression of glucose-6-phosphate dehydrogenase in genetically modified Saccharomyces cerevisiae.
Glucose-6-phosphate dehydrogenase (G6PD) (EC 184.108.40.206) is an abundant enzyme in Saccharomyces cerevisiae. This enzyme is of great interest as an analytical reagent because it is used in a large number of quantitative assays. A strain of S. cerevisiae was genetically modified to improve G6PD production during aerobic culture. The modifications are based on cloning the G6PD sequence under the control of promoters that are upregulated by the carbon source used for yeast growth. The results showed that S. cerevisiae acquired from a commercial source and the same strain produced by aerobic cultivation under controlled conditions provided very similar G6PD. However, G6PD production by genetically modified S. cerevisiae produced very high enzyme activity and showed to be the most effective procedure to obtain glucose-6-phosphate dehydrogenase. As a consequence, the cost of producing G6PD can be significantly reduced by using strains that contain levels of G6PD up to 14-fold higher than the level of G6PD found in commercially available strains.


Inverse relationship between galactokinase activity and 2-deoxygalactose resistance in Chinese hamster ovary cells.
Galactokinase activity is reduced in 12 independent clones of Chinese hamster ovary cells resistant to 2-deoxygalactose. The frequency of resistant colonies is increased with chemical mutagens. The resistant phenotype is stable in the absence of selection. There is an inverse correlation between the levels of galactokinase activity and the cloning efficiency in deoxygalactose. Cells with high resistance have 1% or less of the enzyme activity observed in the parental cells; while cells with low resistance have 10-30% galactokinase activity. Studies with tetraploid hybrid cells reveal that resistance to deoxygalactose is a recessive trait and that cells with high resistance do not complement those with low resistance. In cell lines with low resistance, the Km for galactose, Ki for deoxygalactose, Km for ATP, and thermolability were not significantly altered compared to sensitive parental cells. Although the possibility of mutation at the structural gene locus has not been ruled out, the reduced enzyme activity may also be due to mutation at a regulatory site which affects the number of galactokinase molecules per cell.


RDR2 partially antagonizes the production of RDR6-dependent siRNA in sense transgene-mediated PTGS.
RNA-DEPENDENT RNA POLYMERASE6 (RDR6) and SUPPRESSOR of GENE SILENCING 3 (SGS3) are required for DNA methylation and post-transcriptional gene silencing (PTGS) mediated by 21-nt siRNAs produced by sense transgenes (S-PTGS). In contrast, RDR2, but not RDR6, is required for DNA methylation and TGS mediated by 24-nt siRNAs, and for cell-to-cell spreading of IR-PTGS mediated by 21-nt siRNAs produced by inverted repeat transgenes under the control of a phloem-specific promoter. In this study, we examined the role of RDR2 and RDR6 in S-PTGS. Unlike RDR6, RDR2 is not required for DNA methylation of transgenes subjected to S-PTGS. RDR6 is essential for the production of siRNAs by transgenes subjected to S-PTGS, but RDR2 also contributes to the production of transgene siRNAs when RDR6 is present because rdr2 mutations reduce transgene siRNA accumulation. However, the siRNAs produced via RDR2 likely are counteractive in wildtype plants because impairement of RDR2 increases S-PTGS efficiency at a transgenic locus that triggers limited silencing, and accelerates S-PTGS at a transgenic locus that triggers efficient silencing. These results suggest that RDR2 and RDR6 compete for RNA substrates produced by transgenes subjected to S-PTGS. RDR2 partially antagonizes RDR6 because RDR2 action likely results in the production of counteractive siRNA. As a result, S-PTGS efficiency is increased in rdr2 mutants.


The changes in Tps1 activity, trehalose content and expression of TPS1 gene in the psychrotolerant yeast Guehomyces pullulans 17-1 grown at different temperatures.
The psychrotolerant yeast Guehomyces pullulans 17-1 grows the best at 15 °C. When the yeast cells grown at 15 °C for 48 h were transferred to new medium and grown at 10, 15, and 25 °C, respectively, trehalose-6-phosphate synthase (Tps1) activity and trehalose content of the yeast cells grown at 25 °C were higher than those of the yeast cells grown at 10 and 15 °C. However, Tps1 activity and trehalose content of the yeast cells grown at 10 °C were lower than those of the yeast cells grown at 15 °C. This may suggest that trehalose synthesized by G. pullulans 17-1 only can play more important role in its adaption to high temperature than in its adaption to low temperature. After the GPTPS1 gene encoding trehalose-6-phosphate synthase was cloned from the psychrotolerant yeast, it was found that the promoter of the gene contained several stress-response elements such as C4T and AG4, indicating that the gene expression might be regulated by heat shock. It was also found that the transcriptional level of the GPTPS1 gene in the yeast cells grown at 25 °C was higher than that of the GPTPS1 gene in the yeast cells grown at 10 and 15 °C. However, the transcriptional level of the GPTPS1 gene in the yeast cells grown at 10 °C was lower than that of the yeast cells grown at 15 °C. This meant that expression of the GPTPS1 gene was constant with the changes in Tps1 activity and trehalose content of the yeast cells.


Metastatic renal cell carcinoma in the thyroid gland.
Thyroid incidentalomas on FDG PET/CT are common with one-third of focal uptakes caused by malignancies. Toxic nodules should be excluded. Ultrasound risk-adapted systems can classify thyroid nodules and identify those who need biopsy.


Apoptotic responses stimulated by the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine depend on cell differentiation state in BeWo human trophoblast cells.
During pregnancy, the placental villous cytotrophoblasts differentiate via cell fusion and multinucleation to create syncytiotrophoblasts, a cell type at the maternal-fetal interface. Apoptosis of syncytiotrophoblasts is associated with adverse pregnancy outcomes. The human trophoblast BeWo cell line has been used as an in vitro model for this differentiation process, also known as syncytialization. In the current study, we exposed unsyncytialized BeWo cells, BeWo cells undergoing syncytialization, and syncytialized BeWo cells to S-(1,2-dichlorovinyl)-L-cysteine (DCVC), a metabolite of the industrial chemical trichloroethylene (TCE). DCVC exposure at 50 μM for 48 h decreased cell viability, increased cytotoxicity, increased caspase 3/7 activity, and increased nuclear condensation or fragmentation in BeWo cells regardless of their differentiation status. Investigating mechanisms of apoptosis, DCVC increased H2O2 abundance and decreased PRDX2 mRNA in all three BeWo cell models. DCVC decreased tumor necrosis factor-receptor 1 (TNF-R1) concentration in media and decreased NFKB1 and PRDX1 mRNA expression in syncytialized BeWo cells only. DCVC decreased BCL2 mRNA expression in syncytializing BeWo cells and in syncytialized BeWo cells only. Decreased LGALS3 mRNA was seen in unsyncytialized BeWo cells only. Together, these data suggest roles for oxidative stress and pro-inflammatory mechanisms underlying apoptosis in BeWo cells with differences depending on differentiation state.


Dual effects of entomopathogenic fungi on control of the pest Lobesia botrana and the pathogenic fungus Eutypella microtheca on grapevine.
Entomopathogenic fungi (EPF) are the natural enemies of insect pests. Nevertheless, research on the use of EPF for simultaneous prevention of pest and disease agents on the same crop is limited. In this study, we explored the potential dual effects of three strains of the EPF Metarhizium anisopliae on the control of detrimental agents of Vitis vinifera L., including different developmental stages (larvae, pupae, and adult) of the insect pest Lobesia botrana and the phytopathogenic fungus Eutypella microtheca. Laboratory pathogenicity trials were performed to examine the effects of the three M. anisopliae strains on the mortality rate of L. botrana. In addition, field trials were conducted to assess the biocontrol potential of one selected M. anisopliae strain on the larval stage of L. botrana. Moreover, inhibitory effects of the three EPF strains on E. microtheca growth were examined in vitro. All the M. anisopliae strains were highly effective, killing all stages of L. botrana as well as inhibiting the growth of E. microtheca. The in vitro mortality of larvae treated with the strains was over 75%, whereas that of treated pupae and adults was over 85%. The three EPF strains showed similar efficacy against larvae and adult stages; nevertheless, pupal mortality was observed to be strain dependent. Mortality of L. botrana larvae ranged from 64 to 91% at field conditions. Inhibition of E. microtheca growth reached 50% in comparison to the control. Our study showed that M. anisopliae strains were highly effective in ensuring control of two different detrimental agents of V. vinifera L., providing new evidence to support the dual effects of entomopathogenic fungi.


A long-term follow-up in conservative management of unilateral ureteropelvic junction obstruction with poor drainage and good renal function.
The aim of the study was to retrospectively review the outcome of neonatal ureteropelvic junction obstruction with a good renal function and a poor drainage at a first diuretic renal scan, in cases where surgery was recommended on the basis of a loss of renal function, worsening of hydronephrosis or occurrence of clinical symptoms. Hydronephrosis was graded from 1 to 4 or as ureteral tract dilatation (UTD) P1 to UTD P3. During follow-up, 15 out of 38 patients (34.2%) required surgery while 25 out of 38 (65.8%) could have been managed conservatively. In patients with grade 2, 3, and 4 hydronephrosis, the ureteropelvic junction obstruction resolved or improved spontaneously in 100%, 63%, and 33% of cases (in 100% of UTD P1, 67% of UTD P2, and 50% of UTD P3), respectively. The median of follow-up was 14 years. Chi-square test showed a significant relationship between initial grade of hydronephrosis or UTD and the possibility of an efficient conservative management (p = 0.0088 and p = 0.0460).Conclusion: Conservative management can be safely achieved in ureteropelvic junction obstruction with poor drainage. Scheduled controls are needed for early discovery of functional renal deterioration. High-grade hydronephrosis is unlikely to resolve spontaneously and is often accompanied by a loss of renal function during the first years of life. What is Known: • There is controversy about which management should be adopted in infants with unilateral ureteropelvic junction obstruction with poor drainage but good differential renal function. What is New: • Long-term follow-up suggests that conservative management can be safely achieved also in unilateral ureteropelvic junction obstruction with poor drainage in more than 60% of cases, even if high-grade hydronephrosis is unlikely to resolve spontaneously and it is often accompanied by a loss of renal function during the first years of life. In our experience, surgical intervention was required in more than 50% of cases before 1 year of life and in all cases before 3 years of life.


Nucleosomes unwrapped: Structural perspectives on transcription through chromatin.
Transcription of most protein-coding genes requires the passage of RNA polymerase II through chromatin. Chromatin with its fundamental unit, the nucleosome, represents a barrier to transcription. How RNA polymerase II and associated factors traverse through nucleosomes and how chromatin architecture is maintained have remained largely enigmatic. Only recently, cryo-EM structures have visualized the transcription process through chromatin. These structures have elucidated how transcription initiation and transcription elongation influence and are influenced by a chromatinized DNA substrate. This review provides a summary of our current structural understanding of transcription through chromatin, highlighting common mechanisms during nucleosomal traversal and novel regulatory mechanisms that have emerged in the last five years.


Public policies and tax evasion: evidence from SAARC countries.
In compliance with the socioeconomic theory, the study has strived to investigate the impact of economic and non-economic public policies on tax evasion using panel data of 7 SAARC countries covering the period from 1998 to 2015. The study has applied the ordinary least square with fixed effect and random effect models to analyze the data assembled. The result of the study implies that the higher the degree of economic freedoms, the lower the tax evasion. More specifically, the government policies about property rights, monetary freedom, fiscal freedom and investment freedom have a negative influence on taxpayers' choices of tax evasion while financial freedom result shows a positive effect on tax evasion. Additionally, there is a negative impact of public sector governance and religiosity on tax evasion, which implies the higher the public sector governance and the higher the religious faith amid the people, the lower the degree of tax evasion. The findings of the study are supposed to offer the governments, tax authorities, and research scholars the valuable insights into public policies for reducing the tax evasion to a significant extent.


Vascular-platelet and plasma hemostasis regulators from bloodsucking animals.
Saliva of bloodsuckers (leeches, insects, ticks, vampire bats) contains various regulators of some hemostatic stages. This review summarizes information on their structural characteristics and mechanisms of action. Most bloodsuckers are shown to inhibit vascular-platelet hemostasis by blocking collagen-induced platelet adhesion/aggregation. Plasma hemostasis is inhibited by blocking activation of factor X or factor Xa directly.


HIV-1 integrase pharmacophore model derived from diverse classes of inhibitors.
A three-dimensional pharmacophore model has been generated for HIV-1 integrase (HIV-1 IN) from known inhibitors. A dataset consisting of 26 inhibitors was selected on the basis of the information content of the structures and activity data as required by the catalyst/HypoGen program. Our model was able to predict the activity of other known HIV-1 IN inhibitors not included in the model generation, and can be further used to identify structurally diverse compounds with desired biological activity by virtual screening.


A multifunctional pipette for localized drug administration to brain slices.
We have developed a superfusion method utilizing an open-volume microfluidic device for administration of pharmacologically active substances to selected areas in brain slices with high spatio-temporal resolution. The method consists of a hydrodynamically confined flow of the active chemical compound, which locally stimulates neurons in brain slices, applied in conjunction with electrophysiological recording techniques to analyze the response. The microfluidic device, which is a novel free-standing multifunctional pipette, allows diverse superfusion experiments, such as testing the effects of different concentrations of drugs or drug candidates on neurons in different cell layers with high positional accuracy, affecting only a small number of cells. We demonstrate herein the use of the method with electrophysiological recordings of pyramidal cells in hippocampal and prefrontal cortex brain slices from rats, determine the dependence of electric responses on the distance of the superfusion device from the recording site, document a multifold gain in solution exchange time as compared to whole slice perfusion, and show that the device is able to store and deliver up to four solutions in a series. Localized solution delivery by means of open-volume microfluidic technology also reduces reagent consumption and tissue culture expenses significantly, while allowing more data to be collected from a single tissue slice, thus reducing the number of laboratory animals to be sacrificed for a study.


Clinical Restaging and Tumor Sequencing are Inaccurate Indicators of Response to Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer.
Standard of care for patients with muscle-invasive bladder cancer (MIBC) includes neoadjuvant cisplatin-based chemotherapy (NAC) followed by consolidative therapy with either chemoradiation or radical cystectomy (RC). Some patients experience robust pathologic responses to NAC, and these have been reported to associate with somatic mutations in specific gene pathways including DNA damage response genes. To evaluate the ability of post-NAC clinical restaging, with or without tumor sequencing, to predict final RC pathologic staging. We reviewed our institutional review board-approved institutional database to identify patients with MIBC who underwent NAC followed by RC from 2003 to 2016. Following NAC prior to RC, cystoscopy was performed routinely, with resection of residual visible tumor and/or tumor base (transurethral resection [TUR]). For patients with pre-NAC tumor tissue available, tumor sequencing was performed. Outcome measurements and statistical analysis: Clinical restaging and tumor sequencing were evaluated for their ability to predict the final pathologic stage accurately at RC using chi-square or Fisher's exact test. A total of 114 patients underwent restaging TUR following NAC and prior to RC. The diagnostic accuracy of post-NAC clinical restaging including TUR was poor, with 32% of patients being downstaged falsely when compared with their final RC pathology. Forty-nine patients had sequencing of pre-NAC tumor tissue, of whom 32 showed at least one mutation of interest. However, NAC responses and rates of false downstaging did not differ significantly according to tumor mutation status. This study highlights the inaccuracy of post-NAC clinical restaging TUR with or without adjunctive tumor mutation analysis, to assess pathologic residual disease accurately. Caution must be taken when performing post-NAC restaging, especially when considering conservative management strategies such as active surveillance on this basis. Patient summary: Several groups are evaluating whether certain patients, whose bladder cancer responds well to upfront chemotherapy, may be able to forego cystectomy safely. We demonstrate that currently available staging tools and tumor DNA sequencing cannot identify such patients reliably and accurately.


An assessment of ONRAB oral rabies vaccine persistence in free-ranging mammal populations in Ontario, Canada.
ONRAB is a rabies glycoprotein recombinant human adenovirus type 5 oral vaccine developed for application in baits to control rabies in wildlife populations. Prior to widespread use of ONRAB, both the safety and effectiveness of this vaccine required investigation. While previous research has focused on field performance and the persistence and pathogenicity of ONRAB in captive animals, we sought to examine persistence and shedding of ONRAB in populations of free-ranging target and non-target mammals. We collected oral and rectal swab samples from 84 red foxes, 169 striped skunks, and 116 raccoons during 2007 and 2008 in areas where ONRAB vaccine baits were distributed. We also analyzed 930 tissue samples, 135 oral swab and 138 rectal swab samples from 155 non-target small mammals from 10 species captured during 2008 at sites treated with high densities of ONRAB vaccine baits. Samples were screened for the presence and quantity of ONRAB DNA using quantitative real-time PCR. None of the samples that we analyzed from target and non-target species contained quantities of ONRAB greater than 10(3)EU/mL of ONRAB DNA which is a limit that has previously been applied to assess viral shedding. This study builds on similar research and suggests that replication of ONRAB in animals is short-lived and the likelihood of horizontal transmission to other organisms is low.


Prospective cohort of cryobiopsy in interstitial lung diseases: a single center experience.
Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004). Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.


Anti-epileptic drug changes and quality of life in the community.
Changes in anti-epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change patterns and their association with quality of life (QoL), as main outcome measure, in a community-based setting. We assessed a cohort of 248 people with epilepsy identified from community pharmacy records from whom we retrieved AED dispensing history. We assessed all changes in AED use during the 2 years prior to the index date and current QoL using the validated Dutch QOLIE-31 questionnaire. Thirty-one per cent had at least one AED change during the study period, either in drug type or dose. People who changed showed significantly lower QoL (QOLIE score 73 vs 79), especially those who intensified their treatment. Each additional change was associated with a further reduction of 4.9 points in QoL score. AED changes are common practice, even in people with long-standing epilepsy. Frequent changes, as objective measure of epilepsy severity, are associated with a progressively lower QoL. Changes, even in dose, should be monitored in daily clinical practice and used as a red flag that may require adjustments in epilepsy management. This may include earlier referral to a specialized centre for a more thorough evaluation or counselling. AED changes can also be used as an outcome marker in epilepsy research as a proxy of QoL for better translation of drug-efficacy results to general practice.


Movement disorder in hypothyroidism: a case report.
A case of primary hypothyroidism with hemichoreoathetoid movement was presented. After thyroid hormone replacement therapy for a few weeks, the movement disorder decreased dramatically. This abnormal movement may be one of the neurological manifestations of hypothyroidism.


Prevalence of erectile dysfunction (ED) and its risk factors among adult men in a Nigerian community.
This study assesses the prevalence of erectile dysfunction as well as its risk factors. This is a descriptive cross-sectional study among 650 adult males, aged between 18 and 70 years selected by multi-stage sampling technique. Data were obtained from respondents selected from 4 wards in Olorunda local government area of Osogbo in Osun state, Southwest, Nigeria, using pre-tested semi-structured questionnaires. Majority of the respondents were between ages 20-29 years with mean age of 33.6 ± 13.4 years. Most of the respondents [547(91.2%)] were aware of ED and 63.4% of them said it can be treated. The prevalence of ED was 43.8% and factors such as increasing age (p=0.00), hypertension (p=0.000), diabetes mellitus (p=0.000), perineal surgery (p=0.000), alcohol consumption (p=0.000), and smoking (p=0.000) were found to be significantly associated with developing ED. The level of awareness about erectile dysfunction was high among respondents and the prevalence from this study was 43.8%. Factors associated with ED from this study included increasing age, alcohol consumption, hypertension, perineal injury and surgery. Hence, the risk of developing ED can be significantly reduced by educating men about life style modifications such as reduction in alcohol intake and smoking, as well as regular exercises.


Mass Spectra and Yields of Intact Charged Biomolecules Ejected by Massive Cluster Impact for Bioimaging in a Time-of-Flight Secondary Ion Microscope.
Impacts of massive, highly charged glycerol clusters (≳10(6) Da, ≳ ± 100 charges) have been used to eject intact charged molecules of peptides, lipids, and small proteins from pure solid samples, enabling imaging using these ion species in a time-of-flight secondary ion microscope with few-micrometer spatial resolution. Here, we report mass spectra and useful ion yields (ratio of intact charged molecules detected to molecules sputtered) for several molecular species-two peptides, bradykinin and angiotensin II; two lipids, phosphatidylcholine and sphingomyelin; Irganox 1010 (a detergent); insulin; and rhodamine B-and show that useful ion yields are high enough to enable bioimaging of peptides and lipids in biological samples with few-micrometer resolution and acceptable signals. For example, several hundred molecular ion counts should be detectable from a 3 × 3 μm(2) area of a pure lipid bilayer given appropriate instrumentation or tens of counts from a minor constituent of such a layer.


[Uptake and release of fluoride in enamel surface after fluoridation].
After one single application of a sodium monofluorophosphate or sodium fluoride solution (1%) in an in vitro study, the incorporation of fluoride into enamel platelets was determined. Compared with sodium fluoride the increase in the fluoride concentration following the application of sodium monofluorophosphate was significantly lower, whereas the loss of fluoride after four weeks of rinsing with an artificial saliva solution was markedly reduced. The duration of fluoride incorporation may be one of the factors governing the clinical equivalence of both substances. To determine the amount of enamel in which the fluoride content was measured, the elements calcium and phosphor were determined with the aid of nuclear emission spectrometry and compared with photometric phosphate measurements. All three methods produced identical results.


Polycyclic Aromatic Hydrocarbons (PAHs) in honey from stingless bees (Meliponinae) in southern Brazil.
This study evaluated sixteen Polycyclic Aromatic Hydrocarbons (PAHs) considered priority pollutants by the United States Environmental Protection Agency (USEPA) in 13 honey samples from seven Meliponinae species, collected in native forests and industrial areas in southern Brazil. All samples contained at least one PAH. ∑PAHs ranged from 1.4 to 23.3 μg kg-1, where 23 % of samples were above the maximum allowed levels in dietary food for special medical purposes. Furthermore, the Excess Cancer Risk (ECR) ranged from 1.67 × 10-5 to 6.17 × 10-3, and 2.97 × 10-6 to 1.10 × 10-3, according to the Brazilian Institute of Geography and Statistics (IBGE) and Food and Agriculture Organization (FAO) daily intakes, respectively, being 61.54 % and 15.38 % of the samples above the threshold classified into sever by the USEPA. Results highlighted that honey has been affected by PAH contamination and that it has the potential to be used as an indicator of environmental pollution.


Lipid Nanoparticles Vectorized with NFL-TBS.40-63 Peptide Target Oligodendrocytes and Promote Neurotrophin-3 Effects After Demyelination In Vitro.
Promoting remyelination in multiple sclerosis is important to prevent axon degeneration, given the lack of curative treatment. Although some growth factors improve this repair, unspecific delivery to cells and potential side effects limit their therapeutic use. Thus, NFL-TBS.40-63 peptide (NFL)-known to enter specifically myelinating oligodendrocytes (OL)-was used to vectorize 100 nm diameter lipid nanoparticles (LNC), and the ability of NFL-LNC to specifically target OL from newborn rat brain was assessed in vitro. Specific uptake of DiD-labeled NFL-LNC by OL characterized by CNP and myelin basic protein was observed by confocal microscopy, as well as DiD colocalization with NFL and with Rab5-a marker of early endosomes. Unvectorized LNC did not significantly penetrate OL and there was no uptake of NFL-LNC by astrocytes. Canonical maturation of OL which extended compacted myelin-like membranes was observed by transmission electron microscopy in cells grown up to 9 days with NFL-LNC. Endocytosis of NFL-LNC appeared to depend on several pathways, as demonstrated by inhibitors. In addition, vectorized NFL-LNC adsorbed on neurotrophin-3 (NT-3) potentiated the proremyelinating effects of NT-3 after demyelination by lysophosphatidyl choline, allowing noticeably decreasing NT-3 concentration. Our results if they were confirmed in vivo suggest that NFL-vectorized LNC appear safe and could be considered as putative carriers for specific drug delivery to OL in order to increase remyelination.


Insights into the material properties of dragline spider silk affecting Schwann cell migration.
Dragline silk of Trichonephila spiders has attracted attention in various applications. One of the most fascinating uses of dragline silk is in nerve regeneration as a luminal filling for nerve guidance conduits. In fact, conduits filled with spider silk can measure up to autologous nerve transplantation, but the reasons behind the success of silk fibers are not yet understood. In this study dragline fibers of Trichonephila edulis were sterilized with ethanol, UV radiation, and autoclaving and the resulting material properties were characterized with regard to the silk's suitability for nerve regeneration. Rat Schwann cells (rSCs) were seeded on these silks in vitro and their migration and proliferation were investigated as an indication for the fiber's ability to support the growth of nerves. It was found that rSCs migrate faster on ethanol treated fibers. To elucidate the reasons behind this behavior, the fiber's morphology, surface chemistry, secondary protein structure, crystallinity, and mechanical properties were studied. The results demonstrate that the synergy of dragline silk's stiffness and its composition has a crucial effect on the migration of rSCs. These findings pave the way towards understanding the response of SCs to silk fibers as well as the targeted production of synthetic alternatives for regenerative medicine applications.


Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients.
Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients. The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1% according to a time-dependent receiver operating characteristic curve for 5-year survival. Of the 433 patients, 306 (70.7%) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P < 0.001 and P = 0.027, respectively). In the subgroup analysis of the PD-L1-negative patients, PD-L2 positivity was significantly associated with shorter DFS (P = 0.018). The study demonstrated that the clinical characteristics of patients with PD-L1 expression may differ from those of patients with PD-L2 expression, and that both might contribute to poor prognoses. The potential role of PD-L2 expression as a predictive biomarker for response to immunotherapy should be investigated in future studies.


Lessons for circuit function from large insects: towards understanding the neural basis of motor flexibility.
Motor behaviors result from information processing that occurs in multiple neural networks acting at all levels from the initial selection of the behavior to its final generation. A long-standing research interest is how single neural networks can help generate different motor behaviors, that is, the origin of motor flexibility. Modern experimental techniques allow studying neural network activity during the production of multiple motor behaviors. Recent data provide strong evidence that the neural networks controlling insect legs are individually modified in task-dependent and finely tuned fashions. Understanding the mechanistic basis of these neural network modifications will be of particular interest in the upcoming years.


Comparison of characteristics between neuropathic pain and non-neuropathic pain in patients with diabetic carpal tunnel syndrome: A cross-sectional study.
The aim of the study was to compare the clinical characteristics of diabetic carpal tunnel syndrome between patients with neuropathic pain (NeuP) and non-NeuP. We enrolled 276 patients with diabetic carpal tunnel syndrome. Pain symptoms were evaluated using a visual analog scale. Douleur Neuropathique 4, the Neuropathic Pain Symptoms Inventory questionnaire, and the body map were used to assess neuropathic symptoms. Baseline information, clinical manifestations, electrophysiological test results, and psychological status were compared between the neuropathic pain (NeuP) and non-NeuP to identify the risk factor for NeuP occurrence. Results showed that the degree of pain was more severe in NeuP patients than in nociceptive pain patients (p = 0.025). The frequencies of light touch and pinprick were more pronounced in the NeuP group than in the non-NeuP group (light touch: p = 0.001; pinprick: p = 0.004). There were 48 and 27 NeuP patients with extramedian and proximal spread, respectively, whereas in the non-NeuP group, there were 11 and 9 patients, respectively (p = 0.03). Electrophysiological results showed that patients in the NeuP group exhibited greater sensory nerve conduction velocity impairment compared with the non-NeuP group (p = 0.033). Pain Catastrophizing Scale total scores of the NeuP group were significantly higher than those of the non-NeuP group (p = 0.006). Of the 276 diabetic carpal tunnel syndrome patients studied, the majority had NeuP. Furthermore, light touch, electrophysiological test results, and psychological factors were found to be related to NeuP occurrence in patients with diabetic carpal tunnel syndrome.


Low-molecular mimetics of nerve growth factor and brain-derived neurotrophic factor: Design and pharmacological properties.
To overcome the limitations of the clinical use of neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), scientists have been trying to create their low-molecular-weight mimetics having improved pharmacokinetic properties and lacking side effects of full-sized proteins since the 90s of the last century. The efforts of various research groups have led to the production of peptide and nonpeptide mimetics, being agonists or modulators of the corresponding Trk or p75 receptors that reproduced the therapeutic effects of full-sized proteins. This review discusses different strategies and approaches to the design of such compounds. The relationship between the structure of the mimetics obtained and their action mechanisms and pharmacological properties are analyzed. Special attention is paid to the dipeptide mimetics of individual NGF and BDNF loops having different patterns of activation of Trk receptors signal transduction pathways, phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase/extracellular signal-regulated kinase, which allowed to evaluate the contribution of each pathway to different pharmacological effects. In conclusion, data on therapeutically promising compounds being at different stages of preclinical and clinical studies are summarized.


Sequence and transcription map analysis of early region-1 of porcine adenovirus type-3.
The nucleotide sequence of a region of the genome of porcine adenovirus-3 (PAV-3) between map units 1 and 12.2 was determined. The sequenced region included four major open reading frames, and several transcription control elements. Homology studies, using the deduced amino acid sequences of the open reading frames, revealed genes coding for the E1A, E1B 202R, E1B 474R and pIX proteins. The region was characterized by Northern blot analysis and sequencing of cDNA clones. In PAV-3, the E1A region is located between 1.5 and 3.8 map units. Alternate splice donor sites are used to produce four different types of transcripts from the primary transcript of the E1A region. The E1A proteins of PAV-3 contain a consensus zinc finger motif, which was shown to be the principal transactivation region of human adenovirus-5 (HAV-5) E1A proteins. The PAV-3 E1A proteins also contain a retinoblastoma susceptibility protein (pRb) binding motif, which in HAVs interacts with cellular Rb protein to overcome the pRb mediated transcription repression. The E1B region in PAV-3 maps between 4.0 and 12.2 map units, and shares a polyadenylation signal and polyadenylation sites with the gene coding for pIX. A single major and a number of minor mRNA species are produced from the E1B region. The open reading frame (ORF) analysis of cDNA representing major mRNA produced from the E1B region showed two overlapping ORFs corresponding to 19K and 55K ORFs of HAV-2. In PAV-3, the gene coding for pIX is located between 9.9 and 12.2 map units and codes for a protein of 199 amino acids.


N-WASP knockdown upregulates inflammatory cytokines expression in human gingival fibroblasts.
The neuronal wiskott-aldrich syndrome protein (N-WASP) is a member of the wiskott-aldrich syndrome protein (WASP) family. N-WASP plays a vital role in promoting cell migration, receptor signaling and immune inflammatory responses. This study aimed to observe the changes in the expression of inflammatory factors and involving pathways after N-WASP knockdown in human gingival fibroblasts (HGFs). Gingival inflammatory condition of N-WASP knockout mice was evaluated by H&E staining. N-WASP in HGFs was knockdown by siRNA and the best knockdown efficiency was determined by qRT-PCR and immunofluorescence. The mRNA levels of interleukin (IL)-6, IL-8, C-C motif ligand 2 (CCL2), superoxide dismutase 2 (SOD2) and prostaglandin endoperoxide synthase 2 (PTGS2) were evaluated by qRT-PCR after N-WASP knockdown with or without mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) inhibitors. The protein levels of IL-6, IL-8 and CCL2 were assessed by ELISA. Western blotting was used to detect the activation of NF-κB and MAPK signaling pathways. Gingival tissue from N-WASP knockout mice exhibited an inflammatory reaction. The expression of IL-6, IL-8, CCL2, SOD2 and PTGS2 was significantly upregulated after N-WASP knockdown in HGFs for 6, 24 and 48 h, except for the SOD2 at 6 h. N-WASP knockdown significantly activated the signaling pathways of NF-κB and MAPK. The inhibitors of p65, p38, ERK and JNK clearly decreased IL-6, IL-8, CCL2, SOD2 and PTGS2 expression after N-WASP knockdown. These data indicated that N-WASP deficiency in HGFs increases the production of inflammatory cytokine and is regulated via NF-κB and MAPK signaling pathways.


Remediation of soil cadmium pollution by biomineralization using microbial-induced precipitation: a review.
In recent years, with industrial pollution and the application of agricultural fertilizers with high cadmium (Cd) content, soil Cd pollution has become increasingly serious. A large amount of Cd is discharged into the environment, greatly endangering the stability of the ecological environment and human health. The use of microorganisms to induce Cd precipitation and mineralization is an important bioremediation method. Itis highly efficient, has a low cost, enables environmental protection, and convenient to operate. This article summarizes the pollution status, pollution source, biological toxicity and existing forms of Cd, as well as the biomineralization mechanism of microbial induced Cd(II) precipitation, mainly including microbial-induced carbonate precipitation, microbial-induced phosphate precipitation and microbial-induced sulfide precipitation. Factors affecting the bioremediation of Cd, such as pH, coexisting ions, and temperature, are introduced. Finally, the key points and difficulties of future microbe-induced Cd(II) biomineralization research are highlighted, providing a scientific basis and theoretical guidance for the application of microbe-induced Cd(II) immobilization in soil.


Polystyrene microplastic particles: In vitro pulmonary toxicity assessment.
Microplastics (MPs) have become a global environmental concern. Recent studies have shown that MPs, of which the predominant type is often polystyrene (PS; known as PS-MPs), can extend to and affect remote, sparsely inhabited areas via atmospheric transport. Although exposure to inhaled MPs may induce lung dysfunction, further experimental verification of the pulmonary toxic potential of MPs and the mechanism underlying the toxicity is needed. Here we used normal human lung epithelial BEAS-2B cells to clarify the association between pulmonary toxicity and PS-MPs. Results revealed that PS-MPs can cause cytotoxic and inflammatory effects in BEAS-2B cells by inducing reactive oxygen species formation. PS-MPs can decrease transepithelial electrical resistance by depleting zonula occludens proteins. Indeed, decreased α1-antitrypsin levels in BEAS-2B cells suggest that exposure to PS-MPs increases the risk for chronic obstructive pulmonary disease, and high concentrations of PS-MPs can induce these adverse responses. While low PS-MP levels can only disrupt the protective pulmonary barrier, they may also increase the risk for lung disease. Collectively, our findings indicate that PS-MP inhalation may influence human respiratory health.


[Neuropsychiatric symptoms in older adults with and without dementia in urban and rural regions. Results of the 10/66 Dementia Research Group in Mexico].
To describe, in a Mexican sample of urban and rural residents older than 65 years, with and without dementia, the frequency and severity of neuropsychiatric symptoms. This work is part of the multi-center, epidemiological study carried out by the 10/66 Dementia Research Group, with 1,003 subjects from an urban region and 1,000 subjects from a rural region. Neuropsychiatric symptoms were assessed with the abbreviated version of the Neuropsychiatric Inventory (NPI-Q). Eighty six and eighty five dementia cases were found in the urban and rural regions, respectively. Subjects with dementia were more frequently widows, older and less educated, and the ones from the rural region had fewer neuropsychiatric symptoms, compared to the urban region. In both regions all symptoms were more severe in subjects with dementia. A high frequency of affective symptoms (depression and apathy specially) was observed, and irritability and anxiety in second term. The caregiver stress levels were associated with the frequency and severity of symptoms. This is the first study reporting neuropsychiatric symptoms associated with dementia identified by means of culturally validated and population based diagnostic criteria, in Mexican residents of urban and rural settings.


Ascorbate effects on type I procollagen synthesis by human adult skin fibroblasts: different migration positions of type I procollagen chains on SDS polyacrylamide gel after incubation with ascorbate.
The effects of ascorbate and steroids on type I procollagen synthesis by human skin fibroblasts were studied. Ascorbate treatment (50 micrograms/ml) for 24 hours stimulated a 2-3 fold increase in type I procollagen synthesis and an unexpected shift in the mobility of type I procollagen on SDS polyacrylamide gels. The kinetics of the increase in procollagen synthesis (4 hours) and the shift in electrophoretic mobility (1 hour) were dissimilar, suggesting different controlling mechanisms. This was confirmed by the addition of alpha-alpha'-dipyridyl to ascorbate-treated cultures which eliminated the ascorbate-induced shift in electrophoretic mobility without altering the amount of procollagen synthesis. In contrast, hydrocortisone (1.5 microM) reduced the ascorbate-induced stimulation of type I procollagen synthesis by 80% but did not affect the ascorbate-induced shift in electrophoretic mobility. These studies indicate that the ascorbate-induced increase in type I procollagen synthesis is due to increased levels of type I procollagen mRNA and is independent of the level of hydroxylation of the procollagen.


The Implication of Preoperative Central Stenosis on Patient-Reported Outcomes After Lumbar Decompression Surgery.
To assess the impact of central stenosis severity on patient-reported outcomes after lumbar decompression. Patient diagnosis, demographics, and surgical characteristics were collected via query search and manual chart review of electronic medical records. The inclusion criteria were posterior lumbar decompressions from 2014-2020, with accessible magnetic resonance imaging reports. As previously validated by Lee et al., central stenosis was determined on magnetic resonance imaging and graded as none, mild, moderate, or severe. Patients were dichotomized into 2 groups to improve statistical power for comparisons: none or mild central stenosis and moderate or severe central stenosis. Patient-reported outcome measures (PROMs) were compared between cohorts at 1 year postoperatively. Statistical significance was set at P < 0.05. On bivariate analysis, no significant differences were noted between cohorts with regard to preoperative, 1-year postoperative, and delta PROMs. In addition, no significant difference in the number of patients attaining minimal clinically important difference (MCID) for each PROM was noted between cohorts. With the exception of mental score of the Short Form-12 survey, all intragroup preoperative to postoperative PROMs indicated significant improvement (all P < 0.05) after lumbar decompression surgery. Multivariate regression identified moderate or severe central canal stenosis as a significant independent predictor of improvement in visual analog scale back (estimate = -1.464, P = 0.045). We demonstrate that patients with moderate or severe central spinal stenosis may have more improvement in back pain than those with mild or no central stenosis after lumbar spine decompression surgery.


Rip2 deficiency leads to increased atherosclerosis despite decreased inflammation.
The innate immune system and in particular the pattern-recognition receptors Toll-like receptors have recently been linked to atherosclerosis. Consequently, inhibition of various signaling molecules downstream of the Toll-like receptors has been tested as a strategy to prevent progression of atherosclerosis. Receptor-interacting protein 2 (Rip2) is a serine/threonine kinase that is involved in multiple nuclear factor-κB (NFκB) activation pathways, including Toll-like receptors, and is therefore an interesting potential target for pharmaceutical intervention. We hypothesized that inhibition of Rip2 would protect against development of atherosclerosis. Surprisingly, and contrary to our hypothesis, we found that mice transplanted with Rip2(-/-) bone marrow displayed markedly increased atherosclerotic lesions despite impaired local and systemic inflammation. Moreover, lipid uptake was increased whereas immune signaling was reduced in Rip2(-/-) macrophages. Further analysis in Rip2(-/-) macrophages showed that the lipid accumulation was scavenger-receptor independent and mediated by Toll-like receptor 4 (TLR4)-dependent lipid uptake. Our data show that lipid accumulation and inflammation are dissociated in the vessel wall in mice with Rip2(-/-) macrophages. These results for the first time identify Rip2 as a key regulator of cellular lipid metabolism and cardiovascular disease.


Do varus or valgus outliers have higher forces in the medial or lateral compartments than those which are in-range after a kinematically aligned total knee arthroplasty? limb and joint line alignment after kinematically aligned total knee arthroplasty.
The aims of this study were to determine the proportion of patients with outlier varus or valgus alignment in kinematically aligned total knee arthroplasty (TKA), whether those with outlier varus or valgus alignment have higher forces in the medial or lateral compartments of the knee than those with in-range alignment and whether measurements of the alignment of the limb, knee and components predict compartment forces. The intra-operative forces in the medial and lateral compartments were measured with an instrumented tibial insert in 67 patients who underwent a kinematically aligned TKA during passive movement. The mean of the forces at full extension, 45° and 90° of flexion determined the force in the medial and lateral compartments. Measurements of the alignment of the limb and the components included the hip-knee-ankle (HKA) angle, proximal medial tibial angle (PMTA), and distal lateral femoral angle (DLFA). Measurements of the alignment of the knee and the components included the tibiofemoral angle (TFA), tibial component angle (TCA) and femoral component angle (FCA). Alignment was measured on post-operative, non-weight-bearing anteroposterior (AP) scanograms and categorised as varus or valgus outlier or in-range in relation to mechanically aligned criteria. The proportion of patients with outlier varus or valgus alignment was 16%/24% for the HKA angle, 55%/0% for the PMTA, 0%/57% for the DLFA, 25%/12% for the TFA, 100%/0% for the TCA, and 0%/64% for the FCA. In general, the forces in the medial and lateral compartments of those with outlier alignment were not different from those with in-range alignment except for the TFA, in which patients with outlier varus alignment had a mean paradoxical force which was 6 lb higher in the lateral compartment than those with in-range alignment. None of the measurements of alignment of the limb, knee and components predicted the force in the medial or lateral compartment. Although kinematically aligned TKA has a high proportion of varus or valgus outliers using mechanically aligned criteria, the intra-operative forces in the medial and lateral compartments of patients with outlier alignment were comparable with those with in-range alignment, with no evidence of overload of the medial or lateral compartment of the knee. Cite this article: Bone Joint J 2017;99-B:1319-28.


NT-proBNP cut-off value for ruling out heart failure in atrial fibrillation patients - A prospective clinical study.
N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements can be used to rule out heart failure in patients with sinus rhythm. Atrial fibrillation often coexists with heart failure but affects NT-proBNP levels. This study aims to identify the optimal NT-proBNP cut-off value for ruling out heart failure among atrial fibrillation patients. This prospective study included 409 atrial fibrillation patients admitted to the emergency department. The inclusion criterion was documented atrial fibrillation on a 12‑lead electrocardiogram. All patients completed a NT-proBNP blood sample, a chest X-ray and an echocardiogram. Heart failure was defined as a left ventricular ejection fraction of <40%. In total, 409 patients were included (mean age: 75.2 ± 11.6). The median NT-proBNP level was 2577 ng/L (quartiles: 1185-5438) and 21% had heart failure. We found a lower median NT proBNP level of 3187 ± 3973 ng/L in patients without heart failure compared to 9254 ± 8008 ng/L in patients with heart failure (absolute difference: 4131, 95% (CI): 3299-4986, p < 0.001). The area under the receiver operating characteristic curve for diagnosing heart failure was 0.82 (95% confidence interval: 0.77-0.87). The optimal cut-off value for ruling out heart failure was 739 ng/L with a sensitivity of 99%, a specificity of 18%, and a negative predictive value of 98%. NT-proBNP can be used to rule out heart failure in atrial fibrillation patients with a high negative predictive value, but low specificity. NCT04125966. https://clinicaltrials.gov/ct2/show/NCT04125966.


Environmental Factors, More Than Spatial Distance, Explain Community Structure of Soil Ammonia-Oxidizers in Wetlands on the Qinghai-Tibetan Plateau.
In wetland ecosystems, ammonia oxidation highly depends on the activity of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB), which are, therefore, important for studying nitrogen cycling. However, the ammonia-oxidizer communities in the typical high-elevation wetlands are poorly understood. Here, we examined ammonia-oxidizer communities in soils from three wetland types and 31 wetland sites across the Qinghai-Tibetan Plateau. The amoA gene of AOA and AOB was widespread across all wetland types. Nitrososphaera clade (Group I.1b) overwhelmingly dominated in AOA community (90.36%), while Nitrosospira was the principal AOB type (64.96%). The average abundances of AOA and AOB were 2.63 × 104 copies g-1 and 9.73 × 103 copies g-1. The abundance of AOA amoA gene was higher in riverine and lacustrine wetlands, while AOB amoA gene dominated in palustrine wetlands. The environmental conditions, but not spatial distance, have a dominant role in shaping the pattern of ammonia-oxidizer communities. The AOA community composition was influenced by mean annual temperature (MAT) and mean annual precipitation (MAP), while MAT, conductivity and plant richness, pH, and TN influenced the AOB community composition. The net nitrification rate had a significant correlation to AOB, but not AOA abundance. Our results suggest a dominant role for climate factors (MAT and MAP) in shaping community composition across a wide variety of wetland sites and conditions.


Substantial increase in human immunodeficiency virus (HIV-1) infection in critically ill emergency patients: 1986 and 1987 compared.
In a follow-up study conducted one year after a previous report, we found that 7.8% of 126 patients with critical illness or injury were infected with the human immunodeficiency virus (HIV-1) in 1987 as compared with 3.0% of 203 similar patients in 1986. In the earlier study all patients with infection (six) were confined to a narrow age range (25 to 34 years old) and were trauma presentations. However, in the follow-up study, infections were found in all age groups under 45 years of age (nine) as well as in 3.4% of patients with nontrauma presentations. Infection rates among patients between the ages of 25 and 34 presenting with penetrating trauma remained over 18% during both study periods. While emergency health care providers may have inadvertently interpreted the results of the first study as indicating that the need for infection control precautions could be restricted to young victims of trauma, the follow-up study clearly indicates that appropriate protective measures must be taken on all patients requiring resuscitative measures regardless of age or clinical presentation, particularly in emergency facilities within similar locations.


Pulmonary pleomorphic liposarcoma.
Pulmonary liposarcoma is extremely rare with 6 cases previously reported in the English literature. The following is a report of a 36-year-old man with pulmonary liposarcoma. The patient had chest pain and a mass shadow in the right lower lung field was revealed on a chest X-ray film. A computed tomography and magnetic resonance imaging showed a heterogeneous tumor, compressing the right lower lobe of the lung. Because of the fatty tissue component in the tumor on the chest computed tomography, and the appearance as an extrapulmonary mass, preoperative diagnosis was posterior mediastinal liposarcoma. But thoracotomy revealed that the tumor originated from the lung. Right lower lobectomy and lymph node dissection was carried out with no additional therapy. The pathological diagnosis was pleomorphic liposarcoma originated from the lung. Two months after the operation, the patient died of respiratory failure due to local recurrence.


Retinoic acid and interferon combination studies in human cancer.
Retinoic acid and interferon-alpha have limited single-agent activity in advanced cancer. Cell culture data indicate that in combination these agents have enhanced activity (modulating growth and differentiation) in a number of malignant cell types. Recent clinical work in advanced squamous cell carcinoma reports major activity with this regimen. This paper reviews the preclinical and clinical data testing retinoic acid in combination with interferons and presents recent work integrating these agents with radiotherapy in locally advanced cervical cancer.


Does the St. Jude Regent 17-mm Offer Better Outcomes Than the Hemodynamic Plus 17-mm Aortic Valve Mechanical Prothesis?
The aim of the present study is to report the early and mid-term clinical and hemodynamic results of a prospective trial investigating the clinical performance of the St. Jude Medical Regent 17 mm (SJMR-17) versus St. Jude Medical Hemodynamic Plus 17 mm (SJMHP-17). Between January 2000 and August 2013, 20 patients (Group I) with aortic valve (AV) stenosis underwent first time AV replacement with a SJMR-17 and nine patients (Group II) underwent AV replacement with a SJMHP-17. The mean follow-up was 58 ± 31 months. There was one death in Group I. The end-diastolic IVS thickness and end-systolic posterior left ventricle (LV) wall thickness was reduced significantly in boths groups (p = 0.001 and p = 0.006 in Group I and p = 0.007 and p = 0.011 in Group II). The peak and mean transprosthesis gradients (P-TPG and M-TPG) were 29 ± 6.8 mmHg and 17.5 ± 4.5 mmHg in Group I, significantly lower than in Group II (55.2 ± 19.7 mmHg and 28.8 ± 7.7 mmHg). The postoperative left ventricular mass (LVM) and indexed left ventricular mass (LVMi) were reduced significantly in both groups versus the preoperative values. The postoperative LVMi was 114.5 ± 10.6 g/m(2) in Group I versus 127 ± 8 g/m(2) in Group II (p = 0.01). With dobutamine, heart rate, left ventricular ejection fraction, cardiac output, transprosthesis peak, and mean gradients increased significantly in both groups, however, the P-TPG and M-TPG were significantly higher in Group II (p = 0.026 and p = 0.022) despite a non-significant increase of the indexed effective orifice area. The SJMR-17 can be employed with satisfactory postoperative clinical and hemodynamic outcomes in patients with small aortic annulus, especially in elderly patients offering better outcome than SJMHP-17.


Immediate split-thickness autogenous skin grafts in the horse. Case reports on the treatment of equine sarcoids in 3 horses.
Three horses with equine sarcoids were treated with radical surgical excision and immediate split-thickness skin grafts. Graft take ranged from 50 to 100%, and the epithelial coverage attained resulted in an early functional repair. In no instance was there a recurrence of the sarcoid.


Women with minor menstrual irregularities have increased risk of preeclampsia and low birthweight in spontaneous pregnancies.
Very few studies describe the obstetric and neonatal outcome of spontaneous pregnancies in women with irregular menstrual cycles. However, menstrual cycle irregularities are common and may be associated with increased risk, and women who develop pregnancy complications more frequently recollect irregular menstrual cycles before the time of conception in case-control studies. This retrospective cohort study compares obstetric and neonatal outcomes in spontaneous singleton pregnancies in 3440 primiparous Danish women stratified according to menstrual cycle regularity. All pregnancies delivered after 22 weeks of gestation and had a nuchal translucency examination at Copenhagen University Hospital Hvidovre between 1 January 2009 and 31 December 2010. Menstrual cycle irregularity was defined as more than 7 days' deviation between self-reported and ultrasound examination-based gestational age. Outcome measures were gestational diabetes, hypertension, preeclampsia, preterm premature rupture of membranes, preterm birth, prolonged pregnancy, birthweight, umbilical artery pH <7.1, APGAR <7 after 5 min, admission to neonatal intensive care unit and stillbirth. Women with more than 7 days' deviation between self-reported and ultrasound examination-based gestational age were compared with women with a deviation of 7 days or less. Irregular menstrual cycle before conception increases the risk of preeclampsia (7.9% vs. 5.2%, p < 0.05) and low birthweight (6.0% vs. 3.6%, p < 0.05) in spontaneous pregnancies, but reduces the risk of prolonged pregnancy (1.4% vs. 4.7%, p < 0.001). Irregular menstrual cycle before conception is associated with increased risk of adverse obstetric and neonatal outcome.


Fosfomycin inhibits neutrophil function via a protein kinase C-dependent signaling pathway.
We investigated effects of fosfomycin (FOM) on neutrophil function, specifically the oxidative burst and adhesion molecule expression (CD11b/CD18, or MAC-1) using flow cytometry assay. Preincubation of polymorphonuclear leukocytes (PMNL) with FOM from 1 to 100 microg/ml prior to stimulation by phorbol 12-myristate 13-acetate (PMA, 2 ng/ml) significantly suppressed the oxidative burst in a concentration-dependent manner. However, FOM did not affect the oxidative burst of PMNL stimulated by a chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP). Stimulation with PMA (2 ng/ml) caused a rapid up-regulation of CD11b surface expression on PMNL, followed by time-dependent loss of this receptor. FOM also suppressed loss of CD11b in PMNL stimulated by PMA. FOM then inhibits the PMA-induced oxidative burst and CD11b epitope loss in PMNL. The suppressive effect appears to be mediated by the protein kinase C-dependent signaling pathway.


Controversies in Implant Surgery.
Dental implants are a mainstream treatment protocol to replace missing teeth. Patient and clinician demands have led to shorter length and narrower diameter implants, immediately placed implants into infected sites, and the use of implants in children. This article reviews some of the controversial topics in implant dentistry, and presents the evidence that supports and challenges these newer techniques. Because long-term studies are often not available, especially for implants in infected sites, mini implants, and implants in the growing patient, the field continues to evolve.


The cholesterol-saturated fat index for coronary prevention: background, use, and a comprehensive table of foods.
The potential of a food or a diet to raise the plasma level of total and low-density-lipoprotein cholesterol and to promote atherosclerosis is directly related to its cholesterol and saturated fat content. A new formula that indicates the concentrations of cholesterol and saturated fat in foods, termed the cholesterol-saturated fat index (CSI), has been devised. A low CSI indicates low saturated fat and/or cholesterol content and thus hypocholesterolemic and low atherogenic potential. Guidelines are provided for using the CSI to evaluate or plan low-fat diets, for comparing a food or a mixed dish with others, and for evaluating a day's food intake. A comprehensive table of foods is presented.


Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3p.
Exosomes are potent vehicles for intercellular communication. Rheumatoid arthritis (RA) is a chronic systemic disease of unknown etiology. Local administration of miR-124 precursor to rats with adjuvant-induced arthritis suppresses systemic arthritis and bone destruction. Thus, exosomes may be involved in this disease. We aimed to determine the role of exosomes in the pathology of RA. Fibroblast-like synoviocytes (FLS) were collected from patients with RA and osteoarthritis (OA). miR-124-3p mimic was transfected into the RA FLS (RA miR-124 FLS). Exosomes were collected from the culture medium by ultracentrifugation. Macrophages were produced from THP-1 cells. MicroRNAs in the exosomes were analyzed using real-time PCR. Proteomics analysis was performed using nanoscale liquid chromatography-tandem mass spectrometry. Macrophage migration was evaluated using a Transwell migration assay. SiRNA was used to knockdown proteins of interest. MicroRNAs in the RA FLS, RA miR-124 FLS, and OA FLS exosomes were similar. Proteomics analysis revealed that pentraxin 3 (PTX3) levels were higher in RA FLS exosomes than in RA miR-124 FLS and OA FLS exosomes, and proteasome 20S subunit beta 5 (PSMB5) levels were lower in RA FLS exosomes than in RA miR-124 FLS and OA FLS exosomes. The RA FLS exosomes promoted and the RA miR-124 FLS exosomes suppressed macrophage migration. PTX3-silenced RA FLS exosomes suppressed and PSMB5-silenced OA FLS exosomes promoted macrophage migration. RA FLS exosomes promote macrophage migration via PTX3 and PSMB5, and miR-124-3p suppresses this migration.


Antibody homotypic interactions are encoded by germline light chain complementarity determining region 2.
The utilization of avidity to drive and tune functional responses is fundamental to antibody biology and often underlies the mechanisms of action of monoclonal antibody drugs. There is increasing evidence that antibodies leverage homotypic interactions to enhance avidity, often through weak transient interfaces whereby self-association is coupled with target binding. Here, we comprehensively map the Fab–Fab interfaces of antibodies targeting DR5 and 4-1BB that utilize homotypic interaction to promote receptor activation and demonstrate that both antibodies have similar self-association determinants primarily encoded within a germline light chain complementarity determining region 2 (CDRL2). We further show that these determinants can be grafted onto antibodies of distinct target specificity to substantially enhance their activity. An expanded characterization of all unique germline CDRL2 sequences reveals additional self-association sequence determinants encoded in the human germline repertoire. Our results suggest that this phenomenon is unique to CDRL2, and is correlated with the less frequent antigen interaction and lower somatic hypermutation associated with this loop. This work reveals a previously unknown avidity mechanism in antibody native biology that can be exploited for the engineering of biotherapeutics.


Evaluation of adhesions after laparoscopic myomectomy using the Harmonic Ace and the auto-crosslinked hyaluronan gel vs Ringer's lactate solution.
To evaluate the efficacy of a crosslinked hyaluronic acid (HA) for the prevention of postsurgical adhesions after laparoscopic myomectomy using the Harmonic Ace. Women 23-42 years of age who wished to conceive underwent laparoscopic myomectomy. As adhesion preventing agents, crosslinked HA gel was applied on the myometrial scar at the end of the surgery in Group A, whereas in Group B a Ringer's lactate solution was used in a prospective, observational study. Second-look mini-laparoscopy was performed 45-60 days after surgery and the adhesions were assessed according to a site-specific modified scoring. The incidence of postoperative adhesions was the same in both groups, but anatomically significant adhesions and site-specific modified score was significantly reduced in Group A compared to Group B control group (31.8% vs 54.6% and 1.05 +/- 1 vs 2.27 +/- 2.5, respectively). The use of auto-cross-linked HA gel confirms a protection on adhesion formation on myometrial wounds, although the degree of this effect appears to be weak. The absence of adnexa adhesions using the HA and a different uterine incision appear remarkable, although a larger number of patients is required to confirm the present findings.


Protective effects of dexmedetomidine in pneumoperitoneum-related ischaemia-reperfusion injury in rat ovarian tissue.
To determine the effects of dexmedetomidine on pneuomoperitoneum-related ischaemia-reperfusion (I/R) injury in rat ovarian tissue. Animals were randomized into three groups: Group S (n=8), no pneumoperitoneum; Group C (n=8), pneumoperitoneum; and Group D (n=8), 100μg intraperitoneal dexmedetomidine 30min before pneumoperitoneum. Ovarian tissue was collected from all rats 30min after desufflation, and fresh frozen for histological and biochemical evaluation. Body weight was similar in all three groups (202.62±28.86, 211.00±14.45 and 212.87±15.71g in Groups S, D and C, respectively). The mean malondialdehyde level was higher in Group C than the other groups (p<0.03). When the histological samples of ovarian tissue were compared, vascular congestion, haemorrhage, follicular cell degeneration and infiltrative cell infiltration scores were higher in Group C compared with the other groups (p<0.05). Significantly lower scores for the histological parameters were found in Group D compared with Group C (p<0.05). Similar scores for follicular cell degeneration and inflammatory cell infiltration were found in Group D and Group S (p>0.05). Although vascular congestion and haemorrhage scores were significantly lower compared with Group C, higher scores were found for Group D compared with Group S (p<0.05). Pneumoperitoneum caused oxidative injury in rat ovarian tissue. Dexmedetomidine reduced oxidative stress and histological injury related to I/R.


Ballroom Dance: Linking Serious Leisure to Successful Aging.
This study explored ballroom dance as serious leisure and successful aging in a sample of community-dwelling older adults. Qualitative procedures were used to explore stories of ballroom dance and successful aging. Participants described positive successful aging and active leisure engagement. Three themes emerged from thematic analyses: (a) Ballroom Dance as Serious Leisure: Its Dimensions; (b) Ballroom Dance: Its Link to Successful Aging; (c) The Affinity: We Love to Dance!. The participants' ballroom dance revealed serious leisure characteristics in conjunction with their successful aging. They loved to dance, self-identified as ballroom dancers, and orchestrated their dance activities within its social world. Future research should examine the relation of successful aging to the social world of ballroom dance.


Effect of a Home-Based Mobile Health App Intervention on Physical Activity Levels in Patients With Heart Failure: A Randomized Controlled Trial.
The use of mobile health applications (apps) is an effective strategy in supporting patients' self-management of heart failure (HF) in home settings, but it remains unclear whether they can be used to reduce sedentary behaviors and increase overall physical activity levels. The aims of this study were to determine the effect of an 8-week home-based mobile health app intervention on physical activity levels and to assess its effects on symptom burden and health-related quality of life. In this study, we collected repeated-measures data from 132 participants with HF (60.8 ± 10.47 years) randomized into a usual care group (n = 67) or an 8-week home-based mobile health app intervention group (n = 65). The intervention was tailored to decrease the time spent in sedentary behavior and to increase the time spent in physical activities performed at light or greater intensity levels. Physical activity levels were monitored for 2 weeks before the intervention and during the 8-week intervention using the Samsung mobile health app. Heart failure symptom burden and health-related quality of life were assessed at baseline, 2 weeks from baseline assessment, and immediately post intervention. At week 8, all participants in the intervention group demonstrated an increase in the average daily step counts above the preintervention counts (range of increase: 2351-7925 steps/d). Only 29 participants (45%) achieved an average daily step count of 10 000 or higher by week 6 and maintained their achievement to week 8 of the intervention. Repeated-measures analysis of variance showed a significant group-by-time interaction, indicating that the intervention group had a greater improvement in physical activity levels, symptom burden, and health-related quality of life than the usual care group. Home-based mobile health app-based interventions can increase physical activity levels and can play an important role in promoting better HF outcomes.


Application of multi-parameter population model based on endogenous population biomarkers and flow volume in wastewater epidemiology.
The consumption or prevalence of acesulfame, caffeine, paracetamol and amantadine was estimated by wastewater-based epidemiology based on a multi-parameter population model in 20 sewage treatment plants (STPs) in Hebei province, China. To minimize the uncertainties contributed by population estimation in WBE, a multi-parameter population model was established based on the population biomarkers equivalent population and flow volume-population with the weight factors calculated by the analytic hierarchy process (AHP). 4-Pyridoxic acid (4-PA), cotinine, trans-3'-hydroxycotinine (trans-3'-OH-Cot) and 1,4-methylimidazole acetic acid (MIAA) were selected as population biomarkers. The estimated model population showed the highest correlations (r2 = 0.97, p < 0.01) and lowest variation (one way-ANOVA, p = 0.82, mean variation: -0.1%) comparing to the census data, suggestion better population estimation. The estimated consumption of acesulfame, caffeine, paracetamol and amantadine was 6.7 ± 2.4 mg/day/inh, 50.5 ± 38.5 mg/day/inh, 61.5 ± 52.7 mg/day/inh and 0.52 ± 0.33 mg/day/inh, respectively. Meanwhile, the prevalence of paracetamol and amantadine was calculated to be 5.3% ± 4.5% and 0.28% ± 0.18%, respectively. The estimated results were consistent with that of previous researches in China and were also in accordance with the consumption calculated by sales data (acesulfame and paracetamol). Moreover, uncertainty study showed decrease in population-associated uncertainties by using a multi-parameter population model. The results demonstrated that the multi-parameter population model constructed in this research is feasible to apply in WBE and might lead to lower uncertainties in population estimation.


Safety and efficacy of sufentanil combined with midazolam in bronchoscopy under conscious sedation: retrospective study of 11,158 cases.
The recommended conscious sedation for bronchoscopy is still lacking. The safety and efficacy of sufentanil combined with midazolam in bronchoscopy under conscious sedation is not well elucidated. A retrospective analysis was conducted on patients who received bronchoscopy in the First Affiliated Hospital of Guangzhou Medical University from September 2013 to July 2017. Sufentanil and midazolam were administrated for conscious sedation. The drug dosage, sedating effect and adverse event were collected and analyzed. Totally, 7,089 males and 4,069 females aged 54±16 years (ranged from 4 to 94 years) were enrolled in this study. The dosage of sufentanil and midazolam were 5.25±1.28 mcg (2-13 mcg) and 2.03±0.51 mg (0.5-4.5 mg), respectively. Ninety-eight point six percent (10,998/11,158) of bronchoscopies were successfully completed, while 68.7% (7,670/11,158) procedures were performed with initial dose of 5 mcg sufentanil and 2 mg midazolam. Endobronchial biopsy, transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA), therapeutic procedure and asthma were predictors of giving incremental doses of sufentanil and midazolam (all OR >1, P<0.05), whereas, the age was associated with lower incidence of adding dose of sufentanil and midazolam (both OR <1, P<0.05). Patients with chronic obstructive lung disease (COPD) had lower incidence of adding dose of midazolam alone (OR =0.597, P=0.003). Whereas, female and pulmonary infection were predictors of adding dose of sufentanil alone (OR >1, P<0.05). The conscious sedation related adverse events were not observed. Sufentanil combined with midazolam was safe and effective for bronchoscopy under conscious sedation.


Long-term follow-up of the Copeland mark III shoulder resurfacing hemi-arthroplasty.
Shoulder humeral resurfacing is being performed in increasing numbers. We report the long-term outcome of patients with the Copeland mark III humeral resurfacing hemi-arthroplasty. Ninety-five shoulder hemi-arthroplasties were performed in 85 patients, from 1994 to 2003. Oxford Shoulder Score (OSS) and short form 12 (SF-12) questionnaires were administered. At 12-year follow-up, 49 patients were alive. The OSS was 35.2 and SF-12 score was 83. There were 3 revision operations and 95% survivorship at 18 years. This prosthesis has a low revision rate with few post-operative complications and good patient-reported outcome in an elderly population.


Botulinum toxin therapy: past, present and future developments.
Although botulinum toxin (BT) is now being used in a large number of different indications in numerous medical specialties, there is still dynamic and rapid development. Treatment algorithms were improved by the introduction of BT short-interval therapy, BT high-dose therapy and improved dosing guidelines. Ultrasound guidance may be helpful in special situations. New indication areas including depression and inflammatory processes are being explored. Drug development projects are mainly focusing on onabotulinumtoxinA analogues, some are addressing liquid preparations and modifications of BT's duration of action. Recombinant BT may simplify production processes. Cell-based assays for potency measurement will soon be required by registration authorities. Treatment algorithms will be further refined and indications will be expanded. New indication areas are still uncertain. BT type A will remain the drug substance of choice. Removal of complexing proteins seems logical. Whether there is a need for BT drugs with modified duration of action and for liquid preparations, is unclear. Bringing BT therapy to those who need it, is the biggest challenge. Current high-price business models need to be changed, either by employing a biosimilar registration approach or by referring to companies from countries where business models are based on different cost structures.