Parent-adolescent attachment and peer attachment associated with Internet Gaming Disorder: A longitudinal study of first-year undergraduate students.
Given that Internet Gaming Disorder (IGD) has tentatively been included in DSM-5 as a psychiatric disorder, it is important that the effect of parental and peer attachment in the development of IGD is further explored. Utilizing a longitudinal design, this study investigated the bidirectional association between perceived parent–adolescent attachment, peer attachment, and IGD among 1,054 first-year undergraduate students (58.8% female). The students provided demographic information (e.g., age, gender) and were assessed using the nine-item Internet Gaming Disorder Scale and the Inventory of Parent and Peer Attachment. Assessments occurred three times, six months apart (October 2017; April 2018; October 2018). Cross-lagged panel models suggested that IGD weakly predicted subsequent mother attachment but significantly negatively predicted father attachment. However, father and mother attachment did not predict subsequent IGD. Moreover, peer attachment had a bidirectional association with IGD. Furthermore, the model also demonstrated stable cross-sectional negative correlations between attachment and IGD across all three assessments. The findings of the present study did not show a bidirectional association between parental attachment and IGD, but they did show a negative bidirectional association between peer attachment and IGD. The results suggested previous cross-sectional associations between IGD and attachment, with larger links among males than females at the first measurement point. We found that peer attachment negatively predicted subsequent IGD, which indicates that peer attachment plays an important role in preventing addictive gaming behaviors for university students.


A quantitative description of end-plate currents in the presence of two lidocaine derivatives.
1. Possible ways in which local anaesthetics may act to produce their characteristic alterations of end-plate current (e.p.c.s) are considered. 2. Following Magleby & Stevens (1972b), it is proposed that when acetylcholine (ACh) binds to its end-plate receptor it induces a conformational change which causes an increased ionic permeability and, thus, the measured e.p.c.; the reverse conformational change which returns the permeability to its resting state is postulated to be the rate-limiting event for e.p.c. decay whether or not local anaesthetics are present. Moreover, it is proposed that the ACh receptor had multiple binding sites and the local anaesthetics can bind to one or more of these sites thereby altering the conformational changes induced when ACh binds to remaining sites. 3. Equations based on this proposal are developed and are shown to provide an accurate description of the entire e.p.c. time couse as modified by eith QX-222 or QX-314. 4. Other models are also discussed; models in which local anaesthetic molecules bind only after receptor activation appear to be ruled out.


Serum YKL-40 is a reliable biomarker for pulmonary alveolar proteinosis.
Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar filling. YKL-40, a chitinase-like protein produced by macrophages and epithelial cells, is increased in patients with interstitial lung diseases. We aimed to evaluate the role of YKL-40 as a biomarker for PAP. A total of 34 patients with autoimmune PAP and 50 healthy controls were studied. YKL-40 was measured by ELISA in serum and bronchoalveolar lavage fluid (BALF). Chitinase coding gene polymorphisms (CHI3L1-329 and -131) were detected by PCR and pyrosequencing. Correlations between serum YKL-40 levels and disease outcome were analysed. Baseline serum and BALF levels of YKL-40 were higher in PAP patients than in controls (286 ± 27 ng/mL vs 42 ± 4 ng/mL, P < 0.0001; 323 ± 36 ng/mL vs 3 ± 1 ng/mL, P < 0.0001, respectively). Serum YKL-40 levels correlated with diffusing capacity of the lung for carbon monoxide (DLCO ) at baseline (P = 0.002) and over time (P < 0.0001). Patients with disease progression had higher baseline serum YKL-40 levels than those who remained stable or improved (P < 0.0001). A baseline cut-off level of 300 ng/mL was predictive of disease progression (HR (hazard ratio): 7.875, P = 0.001). The presence of the G allele was associated with higher serum and BALF levels of YKL-40. YKL-40 is elevated in serum and BALF of PAP patients, and may be of clinical utility to predict outcome in PAP.


Design of a liquid crystal-based aptasensing platform for ultrasensitive detection of tetracycline.
We develop a novel label-free liquid crystal (LC) aptasensor based on intrinsic properties of nematic LCs for ultra-sensitive detection of tetracycline. The aptasensor is assembled by immobilizing aptamers onto the glass slide modified with both homeotropic alignment and silane coupling agents. Designed aptasensor makes use of the target-induced aptamer conformational switching and disruption of the orientation of LCs which lead to an obvious change of the optical appearance from a dark to a bright response. We describe the optimized condition for maintaining the homeotropic orientation of LCs, which are suitable for the tetracycline detection. The average gray-scale intensities of polarizing optical microscopy images were calculated to quantitatively detect tetracycline concentrations. The aptasensor works especially at trace level of tetracycline as low as 0.5 pM. Moreover, the LC aptasensor was successfully used to detect tetracycline in the real milk sample. According to the results, the proposed LC aptasensor for tetracycline detection is simple, ultra-sensitive, label free and ease of preparation.


Development of a bacterial surface display of hexahistidine peptide using CS3 pili for bioaccumulation of heavy metals.
A novel cell surface display system for metal uptake was developed using CS3 pili of enterotoxigenic Escherichia coli, which is a suitable system for display of heterologous peptides. The recombinant bacteria producing the hybrid pili containing the hexahistidine peptide accumulated high concentrations of Cd(2+) and Ni(2+) at 656.2 and 276.5 nmol per mg dry weight of bacterial cell, respectively. The recombinant bacteria may be useful in water and waste water treatment.


Application of phase-field fracture theories and digital volume correlation to synchrotron X-ray monitored fractures in human trabecular bone: A case study.
Fracture processes of trabecular bone have been studied using various approaches over the years. However, reliable methods to analyse fracture at the single trabecula level are limited. In this study, a digital volume correlation (DVC) and a phase-field fracture model are applied and contrasted for human trabecular bone to analyse its failure under global compression at high resolution. A human trabecular bone sample was fractured in situ under synchrotron-based X-ray micro computed tomography (CT). Reconstructed CT data was then used in DVC algorithms to obtain high-resolution displacement fields in the bone at different load steps. A high-resolution specimen-specific structural mesh was discretized from the CT data and used for the phase-field simulation of the fracturing bone. The DVC analysis showed opening mode cracks as well as shear mode cracks. Strains in cracked regions were analysed. The load distribution in the trabecular structure resulted in two completely separated fracture regions in the sample body. A phenomenon that was also captured in the phase-field model. The results encourage us to believe improvements in boundary conditions and material models are worthwhile pursuing. Findings in this study support further development of a phase-field method to analyse fracture in samples with complex morphology, such as trabecular bone, and the capacity of DVC to quantify strains and slowly growing stable fractures during step-wise loading of trabecular bone.


Thyrotropin and norepinephrine stimulate the metabolism of phosphoinositides in FRTL-5 thyroid cells.
Hormone-induced changes in phospholipid metabolism were examined in a functioning rat thyroid cell line (FRTL-5). Stimulation of FRTL-5 cells, prelabeled with 32P, with TSH or NE resulted in a rapid decrease in the radioactivity of both phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 4-monophosphate (PIP). The effects of TSH on phospholipid metabolism and calcium mobilization are independent of those on adenylate cyclase. This suggests that the TSH receptor may be unique in that it activates enzyme cascades involved in cAMP production and Ca2+ mobilization.


Intracranial aneurysms in pediatric population: a two-center audit.
Intracranial aneurysms (IA) in children are rare, accounting for less than 5% of all IA. Due to their scarcity, the epidemiology is poorly understood and differs from adults in term of clinical presentation, size, location, and origin. Consequently, the treatment strategies are specific and cannot be only based on data from adult series. The aim of our study was to report the characteristics, management, and outcomes of children treated for IA in two university hospitals located in Normandy (France) over the last 17 years and to perform a literature review of this rare pathology. This retrospective study included 18 consecutive children (< 18 years old) admitted with cerebral aneurysm treated in two neurosurgery departments in Normandy, from 2001 to 2018. Computerized tomography and cerebral angiography established the diagnosis. Both endovascular and surgical procedures were discussed in all cases. Data focused on clinical condition at admission, characteristics of the IA, choice of the treatment modalities, and complications. The outcome at follow-up is based on Glasgow outcomes scale (GOS) at 1 year. During the study period, 18 children (mean age: 12.6 years; sex ratio male/female: 2.3) were admitted with 21 IA. Aneurysms had a mean size of 13.6 mm with 4 giant aneurysms and were mostly located in the anterior circulation (16/21). Clinical presentations at onset were sudden symptoms related to a subarachnoid hemorrhage in 13 patients, headaches in 4 patients with giant aneurysm, and asymptomatic in one patient. Among the 13 patients with ruptured IA, 6 presented in poor preoperative condition (Hunt and Hess Grade ≥ 4). Treatment modalities consisted in embolization in 9 patients and surgery in 9 patients including 2 by-pass surgeries in fusiform aneurysms. Complications were similar in the two groups, but two cases of recanalization were observed in the endovascular group. At 1 year of follow-up, 14 children were in good condition (GOS Score > 4) and one died. Three children presented associated IA treated by the same technique as initial aneurysm. Pediatric aneurysm is a different pathology compared with adults, occurring more frequently in male population with a higher proportion of giant aneurysms and aneurysms located in the internal carotid bifurcation. The use of endovascular techniques has progressed in the last years, but surgery was proposed for half of our population.


Completing the purine utilisation pathway of Aspergillus nidulans.
We have previously identified by classical genetics and biochemistry, all the genes of Aspergillus nidulans predicted to be involved in purine utilisation, together with cognate regulatory genes and one gene encoding a novel xanthine hydroxylation activity. In this article we complete the description of the purine utilisation pathway with the identification of the two genes (uaX and uaW) encoding the enzymes catalysing the conversion of the product of urate oxidation by urate oxidase, 5-hydroxyisourate, to optically active allantoin. The identification of these additional genes confirms the complete absence of clustering of the genes involved in purine utilisation in A. nidulans.


A review of environmental and health risks of maleic hydrazide.
The cellular metabolism, acute toxicity, mutagenicity, and carcinogenicity of maleic hydrazide have been reviewed. It seems that this chemical is a mutagen and a carcinogen in cell cultures and animals, but no evidence is available on human carcinogenicity regardless of population exposure in manufacturing, agriculture, and the food chain (i.e., potatoes, potato chips). Because of the level of exposure of the general public to this compound, an epidemiologic survey should be conducted to ascertain possible human health effects. Long-term feeding experiments should be conducted in several animal species to establish whether maleic hydrazide is carcinogenic by this route. Biotransformation and pharmacokinetic studies should be undertaken to obtain better understanding of the chemical's metabolism and excretion. Such investigations would firmly establish whether the tolerance for maleic hydrazide should remain unchanged or whether the use of the compound should be more restricted.


Lipopolysaccharide mitagates methamphetamine-induced striatal dopamine depletion via modulating local TNF-alpha and dopamine transporter expression.
Systemic lipopolysaccharide (LPS) treatment may affect methamphetamine (MA)-induced nigrostriatal dopamine (DA) depletion. This study was undertaken to determine the critical time window for the protective effects of LPS treatment and the underlying mechanisms. An LPS injection (1 mg/kg) 72 h before or 2 h after MA treatment [three consecutive, subcutaneous injections of MA (10 mg/kg each) at 2-h intervals] diminished the MA-induced DA depletion in mouse striatum. Such an LPS-associated effect was independent of MA-produced hyperthermia. TNF-alpha, IL-1beta, IL-6 expressions were all elevated in striatal tissues following a systemic injection with LPS, indicating that peripheral LPS treatment affected striatal pro-inflammatory cytokine expression. Striatal TNF-alpha expression was dramatically increased at 72 and 96 h after the MA treatment, while such TNF-alpha elevation was abolished by the LPS pretreatment protocol. Moreover, MA-produced activation of nuclear NFkappaB, a transcription factor following TNF-alpha activation, in striatum was abolished by the LPS (1 mg/kg) pretreatment. Furthermore, thalidomide, a TNF-alpha antagonist, treatment abolished the LPS pretreatment-associated protective effects. Pretreatment with mouse recombinant TNF-alpha in striatum diminished the MA-produced DA depletion. Finally, single LPS treatment caused a rapid down-regulation of dopamine transporter (DAT) in striatum. Taken together, we conclude that peripheral LPS treatment protects nigrostriatal DA neurons against MA-induced toxicity, in part, by reversing elevated TNF-alpha expression and subsequent signaling cascade and causing a rapid DAT down-regulation in striatum.


Molar enthalpy and molar volume of methylene and benzene homologues in reversed-phase liquid chromatography.
In this study, thermodynamic properties are measured for methylene and benzene homologues in reversed-phase liquid chromatography using octadecylsilica stationary phases and methanol mobile phase. The change in molar enthalpy (delta H degree) is determined from graphs of the logarithm of the capacity factor versus the inverse temperature (15 to 60 degrees C), whereas the change in molar volume (delta V degrees) is determined from graphs of the logarithm of the capacity factor versus pressure (830 to 5000 p.s.i.). For octadecylsilica phases with low bonding density (2.7 mumol m-2), delta H degree and delta V degree are small and are relatively unaffected by temperature and pressure. These thermodynamic parameters are linearly related to the homologue number for the methylene homologues, but not for the benzene homologues. For the ethylene group, delta delta H degree and delta delta V degree are in the order of -0.41 kcal mol-1 and -1.0 cm3 mol-1, respectively, at 30 degrees C. As the bonding density increases (5.4 mumol m-2), the molar volume and molar enthalpy decrease in a significant and nonlinear manner with the homologue number. Moreover, these thermodynamic parameters are markedly affected by temperature and pressure. For the ethylene group, delta delta H degree and delta delta V degree are in the order of -3.65 kcal mol-1 and -14.1 cm3 mol-1, respectively, at 30 degrees C. The theoretical and practical implications of these measurements are discussed with respect to the retention mechanism in reversed-phase liquid chromatography.


Reliability of a new scale for essential tremor.
The objective of this study was to determine the reliability of a new scale for the clinical assessment of essential tremor. The Essential Tremor Rating Assessment Scale contains 9 performance items that rate action tremor in the head, face, voice, limbs, and trunk from 0 to 4 in half-point intervals. Head and limb tremor ratings are defined by specific amplitude ranges in centimeters. Videos of 44 patients and 6 controls were rated by 10 specialists on 2 occasions 1-2 months apart. Inter- and intrarater reliability was assessed with a 2-way random-effects intraclass correlation, using an absolute agreement definition. Inter- and intrarater intraclass correlations for head and upper-limb tremor ranged from 0.86 to 0.96, and intraclass correlations for total score were 0.94 and 0.96. The intraclass correlations for voice, face, trunk, and leg were less robust. This scale is an exceptionally reliable tool for the clinical assessment of essential tremor.


GLP-1 receptor agonists in NAFLD.
Non-alcoholic fatty liver disease (NAFLD) is very common in patients with type 2 diabetes (T2D), with approximately two-thirds having a diagnosis of the disease. Currently, the only validated treatment for NAFLD is weight loss. A number of studies of animal models and human trials have evaluated the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on liver fat content and suggest that the treatment could represent a new alternative for NAFLD management. In this review, our focus is on the main studies regarding the effects of GLP-1RAs on NAFLD. Also, the mechanisms that might explain their beneficial effects on liver diseases are analyzed.


Kinetic resolution of ketoprofen ester catalyzed by lipase from a mutant of CBS 5791.
A biotransformation process was developed for the production of (S)-ketoprofen by enantioselective hydrolysis of racemic ketoprofen ester using the mutant Trichosporon laibacchii strain CBS 5791. A satisfactory result was obtained, in which the E was 82.5, with an ee of 0.94 and a conversion of 0.47 under the optimum hydrolysis conditions [E is enantiomeric ratio, E=ln[1-X(1+ee)]/ln[1-X(1-ee)]; ee is enantiomeric excess, ee=(CS-CR)/(CS+CR): temperature of hydrolysis was 23 degrees C]. The medium used in biotransformation was a mixture of growth broth and biotransformation broth at a ratio of 1:9, the concentration of Tween 80 was 15 g/l, the time of hydrolysis, 72 h. These results are promising for further scale-up. Tween 80 significantly improved lipase enantioselectivity and activity at the optimum concentration.


Effect of transcatheter renal arterial embolization combined with cryoablation on regulatory CD4+CD25+ T lymphocytes in the peripheral blood of patients with advanced renal carcinoma.
To analyze the effect of Argon-Helium cryosurgery (AHCS) combined with transcatheter renal arterial embolization (TRAE) on the differentiation of regulatory CD4+ CD25+ T cell (Treg) and its implication in patients with renal carcinoma. Seventy seven patients are included in the study, and divided into two groups: TRAE group (n=45, receiving TRAE only) and TRAE+cryoablation group (n=32, receiving cryoablation 2-3 weeks after TRAE). The percentage of Treg cells and T lymphocyte subsets (CD4+T, CD8+T, and CD4+T/CD8+T) in the peripheral blood is measured by flow cytometry previous to the therapy and 3 months after therapy. Meanwhile, the extent of tumor necrosis is measured by MRI or CT 1 month after therapy. The percentages of Treg cells of patients in TRAE + cryoablation group decrease from (6.65±1.22)% to (3.93±1.16)%, (t=42.768, P<0.01), and the percentages of CD4+T and CD4+T/CD8+T increase significantly (P<0.01). However, the results of patients in TRAE group show that the percentages of Treg, CD4+T, CD8+T and CD4+T/CD8+T increase slightly although the differences had no statistical significance (P>0.05). The tumor necrosis rate of TRAE+cryoablation group is 57.5%, significantly higher than those of TRAE group, which shows 31.6% (t=6.784, P<0.01). The median survival duration of the TRAE+cryoablation group is 20 months, significantly longer than that of the TRAE group (χ² = 7.368, P<0.01). The decreasing extent of Treg cells is correlated with tumor necrosis rates (r=0.90, P<0.01) and life time (r=0.67, P<0.01). The therapy of TRAE combined with cryoablation contributes to reduce the percentage of Treg cells and improve the immune situation of patients with renal cell carcinoma, which consequently increase tumor necrosis rate and prolong the patients' survival duration.


Time in range correlates glycated albumin measured immediately after 2 weeks of continuous glucose monitoring.
Time in range (TIR), an index of glycemic control and also blood glucose fluctuation, obtained from continuous glucose monitoring (CGM), has been increasing its importance along with the spread of CGM in recent years. For a while, glycated albumin (GA) has been also used as a glycemic control index during about 2-weeks in routine clinical practice. It has not yet been confirmed under optimal condition whether TIR and GA correlates. Clarification of the correlation between TIR and GA, which was measured immediately after 2-weeks of CGM, might be a finding that further supports the utility of TIR. GA was measured at the conclusion of 2-week CGM in 71 diabetes outpatients at our hospital, and the correlation between GA and indices such as TIR obtained from CGM was statistically analyzed. It was found that TIR and time above range (TAR) were significantly correlated with GA. Upon performing multiple regression analysis, TIR, TAR and BMI. indicated a significant regression coefficient with respect to GA. These findings further support the utility of TIR as a marker of glycemic control that it might also be correlated with GA, and also suggest a relation between GA and blood glucose fluctuation.


Recent progress of functional metal-organic framework materials for water treatment using sulfate radicals.
Human health is being threatened by the ever-increasing water pollution. Sulfate radical (SO4•-)-based advanced oxidation processes (SR-AOPs) are rapidly being developed and gaining considerable attention due to their high oxidation potential and selectivity as a way to purify water by degrading organic contaminants in it. Among the catalytic materials that can activate the precursor to generate SO4•-, metal-organic frameworks (MOFs) are the most promising heterogeneous catalytic material in SR-AOPs because of their various structure possibilities, large surface area, ordered porous structure, and regular activation sites. Herein, an in-depth overview of MOFs and their derivatives for water purification with SR-AOPs is provided. The latest studies on pristine MOFs, MOF composites, and MOF derivatives (metal oxides, metal-carbon hybrids, and carbon materials) are summarized. The mechanisms of decomposition of pollutants in water via radical and non-radical pathways are also discussed. This review suggests future research directions for water purification through MOF-based SR-AOP.


Characteristics and mechanisms of Cu(II) biosorption by disintegrated aerobic granules.
Disintegrated aerobic granules (DAG) as an effective biosorbent had great potential to remove Cu(II) from aqueous solution. The effects of solution pH value, contact time, initial Cu(II) concentration on the biosorption were investigated. Kinetic studies indicate that pseudo-second-order model with correlation coefficients of 0.9999 best fits the Cu(II) biosorption process. Investigation of the biosorption mechanisms shows that Cu(II) biosorption is associated with a significant release of Ca(II). The adsorption capacity of extracted extracellular polymeric substances (EPS) was 2.34 times as much as that of pristine DAG, indicating the significant role of EPS in adsorption. In order to determine the role of different functional groups, DAG was chemically modified to block specific functional groups and was then used in the adsorption of Cu(II). The anionic carboxyl group, was identified as the key binding site for the cationic Cu(II). Results reveal that ion exchange is the most important biosorption mechanism but other mechanisms to some extent like electrostatic interaction, involving in functional groups, also play a part.


Complications of Stamey needle suspension for female stress urinary incontinence.
The Stamey bladder neck suspension for stress urinary incontinence in females is thought to be an excellent procedure. However, recent studies revealed that complications of this procedure have not been negligible. In this retrospective study, complications of the Stamey needle bladder neck suspension were examined. The Stamey procedure was performed either alone or in combination with anterior colporrhaphy for 86 female patients with stress urinary incontinence between 1989 and 1999. The mean follow-up period was 37.6 months and the mean age was 59.1 years. We studied the complications postoperatively pointed out by patients' complaint and image examination. The overall incidence of complications was 37.2%. Voiding difficulties and lower abdominal pain were present in 15 cases, respectively. We experienced 2 unusual cases in whom suspensory stitches had to be removed due to abdominal pain. Although the Stamey bladder neck suspension is thought to be an excellent procedure for stress urinary incontinence, surgeons should beware of possible complications and be alert of the symptoms, such as abdominal pain and bladder irritation.


Investigation on the urea deposit formation and thermal decomposition characteristics in the SCR aftertreatment system of a diesel engine.
Selective catalytic reduction is the most efficient and reliable equipment for NOx control in current diesel engines. However, the issue of urea crystallization becomes increasingly serious with the implement of the new emissions standards. In this paper, urea deposit samples collected from engine test bed and tube furnace were characterized by thermogravimetric analysis and Fourier transform-infrared analysis to aid the comprehension of urea deposit formation. Moreover, thermogravimetric tests were conducted to disclose the effects of catalyst on the thermal decomposition processes of urea deposit. The results indicated that less temperature resistant species are formed in the engine test bed than in the tube furnace at conditions with the same temperatures. The main compositions in the World Harmonized Transient Cycle (WHTC) urea deposits are urea, cyanuric acid (CYA) and ammelide, implying that accelerating the decomposition of these species could prevent the accumulation of urea deposit. CuWTi, Cuβ and CuZSM catalysts could lead to increased yield of CYA during pure urea thermolysis. Cuβ, CuWTi and VWTi catalysts tend to promote the thermolysis of CYA while VWTi has the most significant catalytic effects on the thermal decomposition of ammelide and ammeline.


Population Pharmacokinetics of Olanzapine and Samidorphan When Administered in Combination in Healthy Subjects and Patients With Schizophrenia.
A combination of olanzapine and samidorphan was recently approved by the US Food and Drug Administration for the treatment of patients with schizophrenia or bipolar I disorder. Population pharmacokinetic models for olanzapine and samidorphan were developed using data from 11 clinical studies in healthy subjects or patients with schizophrenia. A 2-compartment disposition model with first-order absorption and elimination and a lag time for absorption adequately described concentration-time profiles of both olanzapine and samidorphan. Age, sex, race, smoking status, and body weight were identified as covariates that impacted the pharmacokinetics of olanzapine. A moderate effect of body weight on samidorphan pharmacokinetics was identified by the model but was not considered clinically meaningful. The effects of food, hepatic or renal impairment, and coadministration with rifampin on the pharmacokinetics of olanzapine and samidorphan, as estimated by the population pharmacokinetic analysis, were consistent with findings from dedicated clinical studies designed to evaluate these specific covariates of interest. Food intake did not have a clinically relevant effect on the pharmacokinetics of olanzapine or samidorphan. Consistent with the known metabolic pathways for olanzapine (primarily via uridine 5'-diphospho-glucuronosyltransferase-mediated direct glucuronidation and cytochrome P450 [CYP]-mediated oxidation) and for samidorphan (predominantly mediated by CYP3A4), coadministration of olanzapine and samidorphan with rifampin, a strong inducer of CYP3A4 and an inducer of uridine 5'-diphospho-glucuronosyltransferase enzymes, significantly decreased the systemic exposure of both olanzapine and samidorphan. Severe renal impairment or moderate hepatic impairment resulted in a modest increase in olanzapine and samidorphan exposure.


Alpha-bulnesene, a novel PAF receptor antagonist isolated from Pogostemon cablin.
Alpha-bulnesene is a sesquiterpenoid isolated from the water extract of Pogostemon cablin. It showed a potent and concentration-dependent inhibitory effect on platelet-activating factor (PAF) and arachidonic acid (AA) induced rabbit platelet aggregation. In a radioligand binding assay for the PAF receptor, alpha-bulnesene competitively inhibited [(3)H]PAF binding to the PAF receptor with an IC(50) value of 17.62+/-5.68microM. alpha-Bulnesene also dose-dependently inhibited PAF-induced intracellular Ca(2+) increase in fluo-3/AM-loaded platelets (IC(50) values of 19.62+/-1.32microM). Furthermore, alpha-bulnesene inhibited AA-induced thromboxane B(2) (TXB(2)) formation and prostaglandin E(2) (PGE(2)) formation. These results indicate that the inhibitory effect of alpha-bulnesene on platelet aggregation was due to a dual activity; specifically the chemical blocked PAF-induced intracellular signal transduction and interfered with cyclooxygenase activity, which resulted in a decrease in thromboxane formation. This study is the first to demonstrate that alpha-bulnesene is a PAF receptor antagonist as well as an anti-platelet aggregation agent.


Sodium iodide symporter (NIS)-mediated radiovirotherapy of hepatocellular cancer using a conditionally replicating adenovirus.
In this study, we determined the in vitro and in vivo efficacy of sodium iodide symporter (NIS) gene transfer and the therapeutic potential of oncolytic virotherapy combined with radioiodine therapy using a conditionally replicating oncolytic adenovirus. For this purpose, we used a replication-selective adenovirus in which the E1a gene is driven by the mouse alpha-fetoprotein (AFP) promoter and the human NIS gene is inserted in the E3 region (Ad5-E1/AFP-E3/NIS). Human hepatocellular carcinoma cells (HuH7) infected with Ad5-E1/AFP-E3/NIS concentrated radioiodine at a level that was sufficiently high for a therapeutic effect in vitro. In vivo experiments demonstrated that 3 days after intratumoral (i.t.) injection of Ad5-E1/AFP-E3/NIS HuH7 xenograft tumors accumulated approximately 25% ID g(-1) (percentage of the injected dose per gram tumor tissue) (123)I as shown by (123)I gamma camera imaging. A single i.t. injection of Ad5-E1/AFP-E3/NIS (virotherapy) resulted in a significant reduction of tumor growth and prolonged survival, as compared with injection of saline. Combination of oncolytic virotherapy with radioiodine treatment (radiovirotherapy) led to an additional reduction of tumor growth that resulted in markedly improved survival as compared with virotherapy alone. In conclusion, local in vivo NIS gene transfer using a replication-selective oncolytic adenovirus is able to induce a significant therapeutic effect, which can be enhanced by additional (131)I application.


The impact of mass drug administration and long-lasting insecticidal net distribution on Wuchereria bancrofti infection in humans and mosquitoes: an observational study in northern Uganda.
Lymphatic filariasis (LF) in Uganda is caused by Wuchereria bancrofti and transmitted by anopheline mosquitoes. The mainstay of elimination has been annual mass drug administration (MDA) with ivermectin and albendazole, targeted to endemic districts, but has been sporadic and incomplete in coverage. Vector control could potentially contribute to reducing W. bancrofti transmission, speeding up progress towards elimination. To establish whether the use of long-lasting insecticidal nets (LLINs) can contribute towards reducing transmission of W. bancrofti in a setting with ongoing MDA, a study was conducted in an area of Uganda highly endemic for both LF and malaria. Baseline parasitological and entomological assessments were conducted in 2007, followed by high-coverage LLIN distribution. Net use and entomological surveys were carried out after one year, and final parasitological and entomological evaluations were conducted in 2010. Three rounds of MDA had taken place before the study commenced, with a further three rounds completed during the course of the study. In 2007, rapid mapping indicated 22.3% of schoolchildren were W. bancrofti antigen positive, and a baseline survey during the same year found age-adjusted microfilaraemia prevalence was 3.7% (95% confidence interval (CI): 2.6-5.3%). In 2010, age-adjusted microfilaraemia prevalence had fallen to 0.4%, while antigenaemia rates were 0.2% in children < 5 years and 6.0% in ≥ 5 years. In 2010, universal coverage of mosquito nets in a household was found to be protective against W. bancrofti antigen (odds ratio = 0.44, 95% CI: 0.22-0.89). Prevalence of W. bancrofti larvae in anopheline mosquitoes had decreased significantly between the 2007 and 2010 surveys, but there was an apparent increase in vector densities. A marked reduction in W. bancrofti infection and infectivity in humans was observed in the study area, where both MDA and LLINs were used to reduce transmission. The extent to which LLINs contributed to this decline is equivocal, however. Further work investigating the impact of vector control on anopheline-transmitted LF in an endemic area not benefitting from MDA would be valuable to determine the effect of such interventions on their own.


Serum level of transforming growth factor-beta1 (TGF-beta1) and the expression of TGF-beta receptor type II in peripheral blood mononuclear cells in patients with autoimmune hepatitis.
To evaluate the association of the immunosuppressive effects of transforming growth factor-beta1 (TGF-beta1) with abnormalities in immune regulation in autoimmune hepatitis (AIH), we investigated the serum level of TGF-beta1 and expression of TGF-beta receptor type II (TbetaRII) in peripheral blood mononuclear cells (PBMC) in patients with AIH. Twenty-two patients with AIH were included in this study. Serum levels of total TGF-beta1 were determined using a specific enzyme-linked immunosorbent assay (ELISA). The expression levels of TbetaRII mRNA were semi-quantitatively determined by ribonuclease (RNase) protection assay specific for TbetaRII. The mean serum level of TGF-beta1 in patients with AIH (230+/-95 ng/mL) was higher than that of healthy controls (137+/-81 ng/mL, p=0.012). The expression level of TbetaRII mRNA in PBMC obtained from AIH patients (0.131+/-0.046) was lower than that in PBMC of patients with chronic hepatitis C (0.186+/-0.074, p=0.019) and that of healthy subjects (0.188+/-0.060, p=0.013). The present study of TbetaRII mRNA expression in PBMC from patients with AIH suggested that the decreased expression of TbetaRII might contribute partially to abnormalities in immune regulation observed in patients with AIH, despite concomitant up-regulation of TGF-beta1 production.


Spectrum of cutaneous hyperalgesias/allodynias in neuropathic pain patients.
The aim of this study was to discern the pathophysio-logical bases for neuropathic hyperalgesias. In this study, neurological and neurophysiological evaluation of 132 consecutive hyperalgesia patients using rigorous clinical and laboratory protocols were carried out. Two discrete semeiologic entities emerged: classic neurological vs atypical, fulfilling taxonomically complex regional pain syndrome (CRPS) II and I, respectively. The classic group (34.9%) exhibited sensorimotor patterns restricted to nerve distribution and documented nerve fiber dysfunction. Among them four (3.03%) had sensitization of C-nociceptors, seven (5.3%) had central release of nociceptive input, and 35 (26.52%) probable ectopic nerve impulse generation. The atypical group (65.1%) displayed weakness with interrupted effort; non-anatomical hypoesthesia and hyperalgesia; hypoesthesia or paresis reversed by placebo, or atypical abnormal movements, and physiological normality of motor and sensory pathways. Spatiotemporal features of neuropathic hyperalgesia constitute key criteria for differential diagnosis between CRPS II and I and, together with other behavioral sensorimotor features, signal psychogenic pseudoneurological dysfunction vs structural neuropathology. 'Neuropathic' hyperalgesias may reflect neuropathological or psychopathological disorders.


Defining and investigating difficult asthma: developing quality indicators.
There is no agreed definition of 'difficult asthma' or what investigations should be available to investigate these patients. Patients with difficult asthma remain symptomatic on high levels of treatment and are high users of medical resources. To develop a set of quality indicators for the definition and investigation of difficult asthma. Modified RAND Appropriateness Method was used. An expert panel composed of nine hospital asthma specialists who run 'difficult' asthma clinics and were identified from a short list of key workers in the field. Indicators were rated as necessary to define and investigate difficult asthma. Difficult asthma was defined as 'symptoms persisting beyond therapy consistent with step 4 of the British Thoracic Society (BTS) guidelines' (high dose inhaled corticosteroids and long acting beta(2)-agonists). Eighty-three indicators were identified (40 relating to definition and 43 relating to investigations). Of these 32 (39%) were rated as necessary: 7 out of 40 (18%) for defining difficult asthma and 23 out of 43 (53%) for investigations. Indicators of high medical resource usage were characteristic of the 'difficult' nature of the management of patient with difficult asthma. A framework for the investigation of these patients was created. The listed performance indicators identify a range of requirements that are necessary to define difficult asthma. Targeting of real needs in this group of patients will lead to better patient care and reduction of 'waste' in provision of healthcare.


Spontaneous arterial lesions: their possible role in arteriosclerosis.
Spontaneous lesions of the arterial wall involving the internal elastic lamellae and variable amounts of the intima are described in the spontaneously hypertensive rat caudal, renal, and mesenteric arteries. A simple model for producing similar circumferential lesions in rat and rabbit carotid arteries has been developed and the subsequent repair of these lesions is described. Two types of circumferential lesion can be produced by the application of 50-160 g of longitudinally applied tension. Small lesions can be up to 400 micron in length and are characterized by the loss of a small area of endothelium and rupture of the internal elastic lamellae. No demonstrable damage to the media is detected in these lesions. Larger lesions can be up to 1 mm in length and are characterized by the loss of endothelium and rupture of the internal as well as a variable number of medial elastic lamellae. Little, if any, damage to the medial smooth muscle cells is observed although the extracellular matrix is often disrupted. Small lesions are completely reendothelialized within 24 hr and larger lesions within 7-10 days. Both large and small lesions repair without the formation of an intimal thickening of smooth muscle cells, despite quite marked damage to the media of the larger lesions.


Neutral alleles at X-linked loci. A cautionary note.
Under the same conditions which yield 1 + 4Nemu as the effective number of neutral alleles maintained by fresh mutation at a rate mu at an autosomal locus in a population of size Ne, the corresponding number at an X-linked locus is 1 + 3Nemu. The resultant bimodal frequency distribution for the effective number of alleles does not seem to have been used as the basis for analysis of data on actual numbers of alleles in natural populations.


Selective transarterial embolization for posttraumatic renal hemorrhage: a second try is worthwhile.
Selective percutaneous transarterial embolization has proved to be effective, safe treatment for posttraumatic renal hemorrhage but inefficacious procedures often lead to nephrectomy. Thus, the success rate of transarterial embolization should be maximized. We retrospectively investigated the clinical success rate of transarterial embolization for posttraumatic bleeding. Study inclusion criteria were imaging evidence and clinical signs of hemorrhage or a hemoglobin decrease of more than 2 gm/dl in urological cases. We excluded spontaneous bleeding from analysis. A total of 21 patients with a median age of 66 years (range 12 to 78) met study inclusion criteria. Etiology was blunt trauma in 3 cases (14%), stab wound in 1 (5%) and an iatrogenic cause in 17 (81%). In 2 patients an active bleeding site could not be detected during selective angiography. Transarterial embolization was done in 19 patients and led to primary clinical success in 12 (63%), including 2 with grade V parenchymal injury. In 6 of 7 cases (86%) in which primary treatment failed transarterial embolization was repeated. It resulted in clinical success in 4 of 6 patients (67%) with equal efficiency (p =1). Three patients (16%) who could not be sufficiently treated with transarterial embolization underwent nephrectomy. When conservative measures fail and clinical symptoms or a relevant hemoglobin decrease occur, transarterial embolization should be considered. Since the success rate is equally high for initial and repeat interventions, re-intervention is justified when the clinical course allows.


Investigations into the interface failure of yttria partially stabilised zirconia - porcelain dental prostheses through microscale residual stress and phase quantification.
Yttria Partially Stabilised Zirconia (YPSZ) is a high strength ceramic which has become widely used in porcelain veneered dental copings due to its exceptional toughness. Within these components the residual stress and crystallographic phase of YPSZ close to the interface are highly influential in the primary failure mode; near interface porcelain chipping. In order to improve present understanding of this behaviour, characterisation of these parameters is needed at an improved spatial resolution. In this study transmission micro-focus X-ray Diffraction, Raman spectroscopy, and focused ion beam milling residual stress analysis techniques have, for the first time, been used to quantify and cross-validate the microscale spatial variation of phase and residual stress of YPSZ in a prosthesis cross-section. The results of all techniques were found to be comparable and complementary. Monoclinic YPSZ was observed within the first 10μm of the YPSZ-porcelain interface with a maximum volume fraction of 60%. Tensile stresses were observed within the first 150 μm of the interface with a maximum value of ≈300 MPa at 50 μm from the interface. The remainder of the coping was in mild compression at ≈-30MPa, with shear stresses of a similar magnitude also being induced by the YPSZ phase transformation. The analysis indicates that the interaction between phase transformation, residual stress and porcelain creep at YPSZ-porcelain interface results in a localised porcelain fracture toughness reduction. This explains the increased propensity of failure at this location, and can be used as a basis for improving prosthesis design.


Intrinsic sympathomimetic activity of pindolol. Evidence for interaction with pretreatment sympathetic tone.
Eighty-six hypertensive patients were treated with pindolol, a beta-adrenergic blocking drug with intrinsic sympathomimetic activity. To evaluate the interactions between beta-blockade, intrinsic sympathomimetic activity, and the level of pretreatment sympathetic activity, blood pressure, heart rate, and forced expiratory volume in one second (FEV1) were examined before and during a 15-week treatment program. The response of patients with a relatively higher pretreatment sympathetic tone reflected by a resting heart rate equal to or greater than 80 beats per minute (Group I) was compared with the response of patients with a lower pretreatment heart rate (less than 80 beats per minute) (Group II). Decreases in mean blood pressure were similar in the two groups. In patients in Group I, the net effect of pindolol was a modest decrease in heart rate and FEV1, supporting the concept that when sympathetic tone is relatively high, the beta-blocking effect is dominant. In contrast, patients in Group II showed little change in heart rate or FEV1 during pindolol treatment, reflecting a balance between the intrinsic sympathomimetic activity and beta-blocking effects of pindolol. Thus, the intrinsic sympathomimetic activity of pindolol is physiologically evident, and relative impact is dependent on the pretreatment level of sympathetic tone.


Instrument development and validation of the comprehensive ability of older people assessment scale.
The study is aimed to develop and psychometrically test the Comprehensive Ability of Older People Assessment scale and classify the ability grades. A cross-sectional design was used for instrument development. The Comprehensive Ability of Older People Assessment scale was developed by a sample of 971 older people from 4 long-term care institutions in China. The data were collected between April 2018 and March 2020. One-way analysis of variance and multiple regression analysis was used to screen scale items, while focus group interviews were used to integrate the subjective and objective items. Confirmative factor analysis and expert judgment were applied to explore construct validity. Reliability was explored through internal consistency estimation using Cronbach's alpha and homogeneity evaluation using corrected item-total correlations. Cluster analysis and discriminant analysis were used to segment the comprehensive ability assessment scores and discriminant function was established to determine the boundary value of each segment, using correlation analysis to perform reverse verification. Factor analysis yielded 40 items with six dimensions, including "mentation and cognitive," "perception and communication," "emotional problems," "mental and behavioural problems," "daily life and social participation," and "skin and oral status." The Cronbach's α was 0.951, while the dimensions showed Cronbach's α values ranging from 0.760-0.946. The rationality and scientificity of this scale were proved by the correlation analysis of reverse validation. The 4-grade Comprehensive Ability of Older People Assessment scale is proved to be with good validity and reliability and should be considered for institutional assessors. Assessors can accurately evaluate older people's health status and nursing needs through this scale in long-term care institutions, communities and hospitals, so as to provide accurate and high-quality nursing services. It will become a scientific basis for the government to offer accurate pension subsidies, purchase pension services scientifically for older people and establish third-party objective evaluation and supervision.


Impact of a case-based collaborative learning curriculum on knowledge and learning preferences of dermatology residents.
Case-based collaborative learning (CBCL) models that incorporate learner-guided content review, structured preparatory assessment, and interactive case-based classroom sessions have been shown to promote content mastery among medical students. However, limited research has explored the viability of CBCL in resident populations, particularly in dermatology. We therefore sought to investigate the impact of a CBCL curriculum covering complex medical dermatology topics on resident knowledge and learning preferences. This prospective cohort study included dermatology and combined internal medicine-dermatology resident trainees of all levels (postgraduate years 2-5) in a single residency program in Boston, Massachusetts. Four CBCL sessions covering complex medical dermatology topics were delivered to program residents between March and April 2019. Preparatory material for each session included a 20-minute concept video and a multiple-choice readiness assessment. During the sessions, residents applied their nascent understanding to newly introduced clinical vignettes and cases covering the preassigned materials. To assess knowledge and learner preferences, 15-question surveys were administered before and immediately after curriculum delivery. Changes in knowledge and learner preferences were determined using Student t tests to compare means and χ2 tests to compare proportions. Of the 30 residents, 29 (96.7%) completed the precurriculum survey and 17 (56.7%) completed the postcurriculum survey. Mean content scores improved significantly (p < .01) from presession (x̅ 5.70; σ 1.88) to postsession (x̅ 9.71; σ 1.88). The majority of respondents indicated a preference for future CBCL sessions, with learning preferences remaining stable over time. In this single-center prospective cohort study, resident knowledge improved significantly after CBCL curriculum delivery. Most resident learners viewed the curriculum as worthwhile and preferred it to traditional lecture-based didactics. Collectively, our findings suggest that CBCL models can be feasibly implemented and durably convey complex content to resident learners.


Simultaneous self-other integration and segregation support real-time interpersonal coordination in a musical joint action task.
The ability to distinguish between an individual's own actions and those of another person is a requirement for successful joint action, particularly in domains such as group music making where precise interpersonal coordination ensures perceptual overlap in the effects of co-performers' actions. We tested the hypothesis that such coordination benefits from simultaneous integration and segregation of information about 'self' and 'other' in an experiment using a musical joint action paradigm. Sixteen pairs of individuals with little or no musical training performed a dyadic synchronization task on a pair of electronic music boxes. The relationship between pitches produced by paired participants (same vs. different) and the relationship between movement frequencies required to trigger synchronous tones (congruent vs. incongruent) were varied in a repeated measures design. The results indicate that interpersonal coordination was most accurate when sounds were different in pitch but movement frequency was congruent. Under other conditions, participants often drifted apart, resulting in poor coordination, especially with same sounds and incongruent movements across co-performers. These findings suggest that interpersonal coordination was facilitated when simultaneous self-other integration and segregation occurred across sensory modalities in an asymmetrical manner where pitch relations favoured segregation via auditory streaming while movement congruence favoured integration via visuo-motor coupling. Such self-other representational balance may enable co-performers to maintain autonomous control while attending, anticipating, and adapting to each other's timing when joint action requires precise temporal coordination.


Chitosan, xanthan and locust bean gum matrices crosslinked with β-cyclodextrin as green sorbents of aromatic compounds.
Three different polysaccharides, xanthan gum, chitosan and locust bean gum, were crosslinked with or without β-cyclodextrin, using citric acid in different ratios, to create 'green' hydrogel matrices. The crosslinking of these polysaccharides was produced through an inexpensive and innocuous solvent-free synthesis process. A favorable swelling behavior of the hydrophilic matrices facilitates the sorption of the solutes tested. Interestingly, the amount of β-cyclodextrin groups is not the only factor to yield the best sorption capability for hydrophobic model molecules: polysaccharides themselves also influence the sorption depending on their characteristic functional groups, the conformation of their chains and, as mentioned above, their degrees of swelling. In order to ascertain the effect of the polysaccharides on the sorption capabilities of a model sorbate (1-naphthol), isotherms using a wide range of solute concentrations were analyzed, and the Hill equation yielded the best fitting results and provided some insight into the mechanisms of interaction.


A study of lactate dehydrogenase isozymes in rat ova.
The presence of subunits A and B has been demonstrated in mature rat ova by several means, including the immunohistochemical method of Coons, use of antisera against LDH-I (B4) and LDH-5 (A4) isozymes, and polyacrylamide gel electrophoresis.


IL-20 bone diseases involvement and therapeutic target potential.
Millions of people around the world suffer from bone disorders, likes osteoporosis, rheumatoid arthritis (RA), and cancer-induced osteolysis. In general, the bone remodeling balance is determined by osteoclasts and osteoblasts, respectively responsible for bone resorption and bone formation. Excessive inflammation disturbs the activities of these two kinds of cells, typically resulting in the bone loss. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory disorders likes psoriasis, atherosclerosis, cancer, liver fibrosis, and RA. IL-20 has an important role in the regulation of osteoclastogenesis and osteoblastogenesis and is upregulated in several bone-related diseases. The anti-IL-20 monoclonal antibody treatment has a therapeutic potential in several experimental disease models including ovariectomy-induced osteoporosis, cancer-induced osteolysis, and bone fracture. This review article provides an overview describing the IL-20's biological functions in the common bone disorders and thus providing a novel therapeutic strategy in the future.


Sensitivity analysis for physiologically based pharmacokinetic models.
The present study evaluates the sensitivity of pharmacokinetic model output to variability in the biochemical and metabolic input parameters. Pharmacokinetic models of three chemicals are chosen for analysis: styrene, methylchloroform, and methylene chloride. Results show that model sensitivities are time-, dose-, and species-dependent and that the most sensitive parameters are the maximum Michaelis-Menten metabolism rate Vmax and the blood/air and fat/air partition coefficients. For humans, the muscle/air partition coefficient is also important. Model output is insensitive to the Michaelis-Menten parameter Km (except for low doses) and to other tissue/air partition coefficients.


Eculizumab treatment and discontinuation in pediatric patients with atypical hemolytic uremic syndrome: a multicentric retrospective study.
Eculizumab is effective treatment of pediatric atypical hemolytic uremic syndrome (aHUS). However, the optimal duration of treatment is not clearly defined. The aim of this study was to retrospectively analyze the outcome of pediatric patients with aHUS, who started eculizumab treatment but discontinued it during the follow-up period. The clinical and laboratory findings of the pediatric patients with aHUS were recorded on a web-based, national registry system, known as the Turkish aHUS Registry. The study included 63 patients who had to have received more than four doses of eculizumab during the acute phase of the disease. The median age at diagnosis was 3.62 (IQR: 1.29-6.14) years. During the follow-up period, 39 patients continued to receive standard eculizumab treatment (standard treatment group, treatment every 2 weeks) while 24 received an extended dose of eculizumab at three-four-week intervals (non-standard treatment group). There was no significant difference between both groups in terms of clinical and laboratory parameters. Eculizumab treatment was discontinued in 18 patients (30.7%, F/M:11/7), and the median age of these patients at diagnosis and their median follow-up duration were 4.0 (IQR:2.7-10.2) and 4.2 (IQR:2.2-7) years respectively. The median eGFR at the last visit was 110 (84.7-146.1)ml/min/1.73 m2. Fourteen patients remained in remission without any sign of the disease. Recurrence occurred in four (22.2%) patients, in which eculizumab was immediately started again and complete remission was achieved. Eculizumab is a successful treatment option in pediatric patients with aHUS and it can be safely discontinued with close monitoring in a selected group of patients. In case of recurrence, eculizumab should be restarted immediately to achieve complete remission.


Natural radioactivity and total K content in wild-growing or cultivated edible mushrooms and soils from Galicia (NW, Spain).
The radioactive isotope, 40K, of naturally occurring potassium (0.012%) is present in the Earth's crust in a low percentage of all potassium, leading to its presence in almost all foodstuffs. The impact of 40K activity concentrations was assessed in wild and cultivated edible mushrooms and in growing substrates. Samples were analysed by gamma spectroscopy. In the wild mushroom species, the average activity concentration of 40K was 1291 Bq kg-1 dry weight (dw), approximately 140 Bq kg-1 fresh weight (fw), with a range of average values per species from 748 in Lactarius deliciosus to 1848 Bq kg-1 dw in Tricholoma portentosum. The cultivated species presented an average value of 1086 Bq kg-1 dw; and the soils, compost of cultivation and wood of substrate are 876, 510 and 59.4 Bq kg-1 dw, respectively. The total K content reached a maximum of 59,935 mg kg-1 dw in T. portentosum. The transfer factors (TF > 1) suggested that mushrooms preferentially bioconcentrated 40K. Cantharellus cibarius, Craterellus tubaeformis, Hydnum repandum and T. portentosum by most TF could be considered as bioindicators of 40K. Taking into account that the annual radiation dose of 40K due to the average consumption of mushrooms analysed (0.15 μSv/year) is very low, it can be concluded that the consumption of these mushrooms does not represent a toxicological risk for human health. Finally, according to the total K content, from the nutritional point of view, these mushrooms could be considered as a potential source of potassium for the human diet.


Combining Direct 3D Volume Rendering and Magnetic Particle Imaging to Advance Radiation-Free Real-Time 3D Guidance of Vascular Interventions.
Magnetic particle imaging (MPI) is a novel tomographic radiation-free imaging technique that combines high spatial resolution and real-time capabilities, making it a promising tool to guide vascular interventions. Immediate availability of 3D image data is a major advantage over the presently used digital subtraction angiography (DSA), but new methods for real-time image analysis and visualization are also required to take full advantage of the MPI properties. This laboratory study illustrates respective techniques by means of three different patient-specific 3D vascular flow models. The selected models corresponded to typical anatomical intervention sites. Routine patient cases and image data were selected, relevant vascular territories segmented, 3D models generated and then 3D-printed. Printed models were used to perform case-specific MPI imaging. The resulting MPI images, direct volume rendering (DVR)-based fast 3D visualization options, and their suitability to advance vascular interventions were evaluated and compared to conventional DSA. The experiments illustrated the feasibility and potential to enhance image interpretation during interventions by using MPI real-time volumetric imaging and problem-tailored DVR-based fast (approximately 30 frames/s) 3D visualization options. These options included automated viewpoint selection and cutaway views. The image enhancement potential is especially relevant for complex geometries (e.g., in the presence of superposed vessels). The unique features of the as-yet preclinical imaging modality MPI render it promising for guidance of vascular interventions. Advanced fast DVR could help to fulfill this promise by intuitive visualization of the 3D intervention scene in real time.


Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules.
Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism. This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.


On some characteristic properties of ATR liquid light conductors.
Electronic spectra of aqueous solutions of the malachite green dye have been measured by liquid and solid spectroscopy. Particular characteristics of the light conductor itself have been shown to have no considerable effect on the results of the experiment.


Biomarkers of macular neovascularisation activity using optical coherence tomography angiography in treated stable neovascular age related macular degeneration.
The aim of this study was to describe features of disease activity in patients with treated stable macular neovascularisation (MNV) in neovascular age related macular degeneration (nAMD) using optical coherence tomography angiography (OCTA). Thirty-two eyes of 32 patients with nAMD were included in this prospective, observational study. These patients were undergoing treatment with aflibercept on a treat-and-extend regimen attending an extension to a 12-week treatment interval. All subjects had no macular haemorrhage and no structural OCT markers of active MNV activity at the index 12-week treatment extension visit. 31/32 OCTA images were gradeable without significant imaging artefact. The mean MNV size was 3.6mm2 ± 4.6mm2 and 27 (87.1%) had detectable MNV blood flow. 29/31 (93.5%) subjects had MNV with mature phenotypes including 10 non-specific, 10 tangle and 3 deadtree phenotypes. MNV halo and MNV central feeder vessel were noted in 18 (58.1%) and 19 (61.3%) of subjects respectively; only 1 (3.2%) subject was noted to have a MNV capillary fringe. MNV blood flow is still detectable using OCTA in the majority of subjects in this study with treated stable MNV. OCTA features associated included MNV mature phenotype, MNV feeder vessel, MNV halo and absence of capillary fringe.


Okadaic acid gives concentration-dependent reciprocal effects on the fluid phase endocytosis activated by Ca2+ and phorbol 12-myristate 13-acetate.
Incubation of a human fibrosarcoma cell line HT-1080 in increasing concentration of Ca2+ was found to enhance endocytic internalization of a fluid phase marker, horseradish peroxidase. At 16.8 mM Ca2+, generation of the effect required incubation for more than 45 min. The effect was reversed by removal of the excess ion for 30 min. Monitoring the intracellular concentration showed that the incubation induced a transient large Ca2+ influx followed by a recovery to 230 +/- 50 nM instead of the normal level of 83 +/- 5 nM. The activation was not inhibited by inhibitors of protein kinases nor a cAMP antagonist. In contrast, the effect was prevented by okadaic acid (OKA) at 100 nM without detectable effect on the basal activity. Fluid phase uptake by HT-1080 cells was also enhanced by phorbol 12-myristate 13-acetate (PMA). In contrast to the case with Ca2+, OKA at 100 nM did not prevent the PMA effect but further enhanced the endocytosis. The effect of OKA was concentration-dependent, as the reagent at 1 microM inhibited not only both the activation but also the basal activity. In Ca(2+)- or PMA-stimulated cells, FITC-dextran was delivered to endosomes that had been labeled with TRITC-transferrin. In contrast, following treatment with a combination of PMA and 100 mM OKA, fluid phase was internalized in vesicular compartments devoid of transferrin labeling. These results suggest that, through differential modifications of protein phosphorylation, endocytosis can be enhanced distinctively either by employing conventional receptor-bearing compartments or generating a new endosomal population.


Inhibition of the growth of yeasts in fermented salads.
Salads composed of vegetables and/or meat in an oil-in-water emulsion were prepared by fermentation for 7 h at 42 degrees C or 45 degrees C with strains of Lactobacillus spp. Their stability towards spoilage yeasts was studied using Saccharomyces cerevisiae, Saccharomyces exiguus and Torulaspora delbrueckii, isolated from salads, as well as Pichia membranaefaciens and Zygosaccharomyces bailii. Salads fermented with good lactic starters usually had pH values of < or = 4.2 and lactic acid concentrations of 0.28 to 0.43% (w/w). High numbers of spoilage yeasts (and production of large volumes of CO2) were not attained in these salads, provided the initial concentration of spoilage yeasts was sufficiently low (< or = 100 CFU/g). Inhibition of spoilage yeasts in lactic fermented salads is probably due to lactic acid, the low storage temperature and the low residual oxygen concentration.


A family of unusual immunoglobulin superfamily genes in an invertebrate histocompatibility complex.
Most colonial marine invertebrates are capable of allorecognition, the ability to distinguish between themselves and conspecifics. One long-standing question is whether invertebrate allorecognition genes are homologous to vertebrate histocompatibility genes. In the cnidarian Hydractinia symbiolongicarpus, allorecognition is controlled by at least two genes, Allorecognition 1 (Alr1) and Allorecognition 2 (Alr2), which encode highly polymorphic cell-surface proteins that serve as markers of self. Here, we show that Alr1 and Alr2 are part of a family of 41 Alr genes, all of which reside in a single genomic interval called the Allorecognition Complex (ARC). Using sensitive homology searches and highly accurate structural predictions, we demonstrate that the Alr proteins are members of the immunoglobulin superfamily (IgSF) with V-set and I-set Ig domains unlike any previously identified in animals. Specifically, their primary amino acid sequences lack many of the motifs considered diagnostic for V-set and I-set domains, yet they adopt secondary and tertiary structures nearly identical to canonical Ig domains. Thus, the V-set domain, which played a central role in the evolution of vertebrate adaptive immunity, was present in the last common ancestor of cnidarians and bilaterians. Unexpectedly, several Alr proteins also have immunoreceptor tyrosine-based activation motifs and immunoreceptor tyrosine-based inhibitory motifs in their cytoplasmic tails, suggesting they could participate in pathways homologous to those that regulate immunity in humans and flies. This work expands our definition of the IgSF with the addition of a family of unusual members, several of which play a role in invertebrate histocompatibility.


Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine.
Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries. Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers. Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways. The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.


Oxyradical scavenging effects of dehydroascorbate.
Dehydroascorbate (DHA) has been shown to possess vitamin C like activities as well as to protect the lens against oxidative stress and cataract formation. The results presented here suggest that some of the beneficial effects of DHA can be attributed to its property of undergoing peroxidative decarboxylation and of O2-. scavenging. Incubation of 1-14C-DHA with peroxide at physiological pH has been found to liberate 14CO2 in quantitative yields, with recovery of 79-94%. The recovery increases with the increase in the amount of DHA used. Its O2-. scavenging activity was apparent by inhibition of O2-. dependent reduction of ferricytochrome c and nitroblue tetrazolium. The authenticity of the latter mechanism was proved by inhibition of the O2-. dependent reactions also by superoxide dismutase.


Segmental copy number variation shapes tissue transcriptomes.
Copy number variation (CNV) is a key source of genetic diversity, but a comprehensive understanding of its phenotypic effect is only beginning to emerge. We have generated a CNV map in wild mice and classical inbred strains. Genome-wide expression data from six major organs show not only that expression of genes within CNVs tend to correlate with copy number changes, but also that CNVs influence the expression of genes in their vicinity, an effect that extends up to half a megabase. Genes within CNVs show lower expression and more specific spatial expression patterns than genes mapping elsewhere. Our analyses reveal differential constraint on copy number changes of genes expressed in different tissues. Dosage alterations of brain-expressed genes are less frequent than those of other genes and are buffered by tighter transcriptional regulation. Our study provides initial evidence that CNVs shape tissue transcriptomes on a global scale.


Glucosamine-mediated immunomodulation after stroke is sexually dimorphic.
Growing evidence suggests that galectin-3 (Gal-3) is instrumental in orchestrating innate immune response and microglia activation following different brain pathologies. However, its role remains controversial. We recently showed that a readily available natural product glucosamine may act as a strong modulator of Gal-3. Glucosamine is a naturally occurring sugar and a precursor in the synthesis of glycosylated proteins. It is often used as a supplement to treat symptoms of various inflammatory conditions. Our recent work suggests that by increasing the synthesis and availability of Gal-3 ligands and/or by regulating its expression levels, glucosamine may significantly modulate Gal-3 signaling. Because evidence suggests that Gal-3 might be differentially regulated after ischemic injury in the brains of female mice, here we examined and compared the immunomodulatory potential of glucosamine in male and female stroke. The mice were subjected to transient middle cerebral artery occlusion (MCAO), followed by different reperfusion periods. The short-term 5 days treatment with glucosamine (150 mg/kg i.p.) was initiated 2 hrs after stroke. To visualize the effects of glucosamine treatment on post-stroke inflammation, we took advantage of a transgenic mouse model bearing the dual reporter system luciferase/GFP under transcriptional control of a murine TLR2 promoter (TLR2-luc-GFP) allowing in vivo bioluminescence imaging of innate immune response and microglial activation. We report that after stroke, both, male and female mice strongly up-regulate the TLR2 bioluminescence signals from activated microglia, however, the observed in vivo immunomodulatory effects of glucosamine after stroke were sex-dependent. Analysis of cytokine profiles at protein level, in glucosamine-treated male mice 72hsr after stroke, revealed down regulation of pro-inflammatory cytokines, an increase in levels of anti-inflammatory cytokines including IL-4, IL13 and colony stimulating factors MCFC and GM-CSF and a significant decrease in the size of ischemic lesion in male mice. Conversely, in female mice glucosamine markedly increases the pro-inflammatory signaling and exacerbates ischemic injury. Analysis of the downstream signaling target of glucosamine/Gal-3 revealed that glucosamine administration restored PPAR-γ activity in male but not in female mice 3 days following MCAO. Together, our results suggest that glucosamine acts as a fine tuner of post-ischemic inflammation in a sex dependent-manner and may have therapeutic potential after stroke in males. Based on our results propose that targeting immune system after stroke may require adapted sex-specific therapeutic approaches.


Affordable, abbreviated roche monitor assay for quantification of human immunodeficiency virus type 1 RNA in plasma.
The cost for the Roche Monitor assay kit can be reduced 50% by using only the 1:1, 1:25, and 1:625 human immunodeficiency virus (HIV) and the 1:1 quantitation standard dilutions. This abbreviated test applied to 1,774 mostly African samples had results nearly identical to those obtained following the package insert instructions. To make this approach feasible, Roche would have to provide additional lysis buffer and master mix.


Ultrastructural and fluorescence microscopy study of a case of acute erythremia.
The authors studies in fluorescence microscopy and electronic microscopy the dysmorphic erythroblasts of a case of acute erythremia. They found evidence of granular fluorescence on the smears, corresponding to the presence of prophyrins and proteinaceous cristallin structures on the ultrathin sections. It seems to be possible to establish a morphologic correlation between the fluorescent granules and the cristallin structures. Thus, the hypothesis of poryphrins adsorption on cristallin structures may be proposed.


Effect of potassium on human and rat liver glucose-6-phosphatase.
Potassium chloride concentrations of 100-150 mM were shown to inhibit (20-40%) human and rat liver microsomal glucose-6-phosphatase when the substrate was reduced to physiological concentration. When the enzyme was solubilized by treatment of microsomes with A12O3 the inhibition could be observed at greater substrate concentrations. Since potassium deprivation is associated with hyperglycemia in both animals and man, these observations may have physiological significance.


Precise control of the interlayer twist angle in large scale MoS2 homostructures.
Twist angle between adjacent layers of two-dimensional (2D) layered materials provides an exotic degree of freedom to enable various fascinating phenomena, which opens a research direction-twistronics. To realize the practical applications of twistronics, it is of the utmost importance to control the interlayer twist angle on large scales. In this work, we report the precise control of interlayer twist angle in centimeter-scale stacked multilayer MoS2 homostructures via the combination of wafer-scale highly-oriented monolayer MoS2 growth techniques and a water-assisted transfer method. We confirm that the twist angle can continuously change the indirect bandgap of centimeter-scale stacked multilayer MoS2 homostructures, which is indicated by the photoluminescence peak shift. Furthermore, we demonstrate that the stack structure can affect the electrical properties of MoS2 homostructures, where 30° twist angle yields higher electron mobility. Our work provides a firm basis for the development of twistronics.


Formation of odorous compounds from hydrogen sulphide and 2-butenal.
Strongly odorous compounds may be formed upon addition of hydrogen sulphide to unsaturated carbonyl compounds. The reaction between hydrogen sulphide and 2-butenal was studied, and the characteristics of the flavour, the structure and some of the physical chemical characteristics of the reaction products were determined. The influence of the pH on the type of components formed in dilute aqueous solution was investigated.


Fabrication of high-aspect-ratio Prussian blue nanotubes using a porous alumina template.
Prussian blue nanotubes were fabricated by using a sequential deposition technique inside the 60-nm well-ordered pores of anodic alumina. By varying the deposition parameters and the dimensions of the template, we could tailor the length and the outer as well as the inner diameter of the tubes. The nanotubes were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD).


The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats.
One of the prominent health problems caused by Aluminium was the decrease in male fertility rates. In the study, the protective effect of Esculetin (ESC) against the reproductive toxicity induced by Aluminium chloride (AlCl3 ) was investigated. For this purpose, AlCl3 was administrated to Wistar Albino rats at a dose of 34 mg/kg and ESC was administrated at a dose of 50 mg/kg for 70 days. It was determined that AlCl3 treatment reduced sperm motility and concentration, increased dead/live rate and abnormal sperm rate. It decreased serum testosterone level, and co-treatment of ESC significantly regulated these values. In the AlCl3 -treated group, MDA level increased and GSH level, GPx and CAT activities decreased compared with those of the control group. However, co-treatment of ESC showed an amelioratory effect on the values except for CAT activity. It was observed that the expression level of NRF-2 increased in the ESC and AlCl3 + ESC groups, and NF-κB increased in the AlCl3 group with the control group. It was determined that Caspase-3 expression decreased, and Bcl-2 expression increased in AlCl3 + ESC group compared to AlCl3 group. It was also determined that AlCl3 -induced tissue injury was significantly prevented by ESC co-treatment.


Preoperative Chemerin Level Is Predictive of Inflammatory Status 1 Year After Bariatric Surgery.
Obesity is associated with chronic low-grade inflammation, which has been linked to increased morbidity. However, inflammation variably and unpredictably improves after bariatric surgery. This study aimed at (1) evaluating the relationship between amplitude of weight loss and variation of inflammatory parameters after bariatric surgery, and (2) identifying, among clinical and biological baseline parameters, predictive factors of variation in inflammatory parameters. In a prospective cohort of patients who underwent bariatric surgery, serum concentrations of interleukin (IL)-6, IL-10, resistin, leptin, adiponectin chemerin, and C-reactive protein (CRP) were measured preoperatively and 1 year after surgery, and routine clinical and biochemical parameters were retrieved. Univariate and multivariate analyses (partial least square method) were performed to assess how parameters were associated with weight loss and to predict improvement of inflammatory parameters. Eighty-seven patients were included (mean weight ± SD 136.3 ± 3.2 kg, 35 gastric bypasses, 52 sleeve gastrectomies). In parallel with weight loss (39.5 ± 13.8 kg), pro-inflammatory markers (IL-6, CRP, leptin, resistin) significantly decreased, and anti-inflammatory markers (IL-10, adiponectin) increased. Multivariate analysis revealed a significant association between weight loss and improvement in inflammatory parameters. Among all the clinical and biological preoperative parameters, baseline chemerin level was the only parameter that was significantly associated with global improvement of the inflammatory status after surgery. The amplitude of weight loss 1 year after bariatric surgery was strongly correlated with improvement of inflammatory profile, which could be predicted by baseline plasma level of chemerin. This suggests a key role of chemerin in obesity-driven inflammation, and a potential use as a biomarker.


Ecofriendly Approach for the Control of a Common Insect Pest in the Food Industry, Combining Polymeric Nanoparticles and Post-application Temperatures.
One of the most common insect pests is Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae), which affects different food commodities. A new effective approach for the management of insect pests is the development of new formulations based on essential oils (EO). However, few works informed about the relationship between insecticidal activity of EO or essential oils loaded polymeric nanoparticles (EOPN) and post-application temperature. In our work, palmarosa [Cymbopogon martinii (Roxb.) Watson], geranium (Geranium maculatum L.), and peppermint (Mentha piperita L.) oils were formulated in a polyethylene glycol 6000 matrix to obtain EOPN. Geranium and palmarosa EOPN had sizes of 259 and 191 nm, respectively; the encapsulation efficiency (EE) was close to 90%, and the samples were monodisperse. The sizes from peppermint EOPN were around 380 nm, with an EE of 72%, and were polidisperse. In a contact toxicity bioassay, the insecticidal effect of the oils was increased by all EOPN, with palmarosa oil being the most toxic. In addition, the oils and their nanoparticles showed a significantly negative temperature coefficient when applied by contact. In a fumigant bioassay, just palmarosa and peppermint EOPN enhanced the oil activity and palmarosa EO and EOPN showed the highest toxic effect. In this case, the EO and EOPN insecticidal activity was unaffected by environmental temperature variation.


Trabecular titanium tailored implants in complex acetabular revision surgeries: our experience at minimum 3 years follow-up.
Hip revision surgery in cases with previous multiple reconstructive procedures is a challenging procedure. A custom-made product could be useful to obtain good results. Four cases (2 men and 2 women) of acetabular customized Trabecular Titanium (TT) implants made by 3D printed technology were performed. The mean age at surgery was 51.5 years (range 25-72). Patients were reviewed clinically and radiographically at follow-up. Mean Harris Hip Score increased significantly from 13.9 (range 6.9-20.6) preoperatively to 75.8 (range 53.9-94) at last follow-up (mean 43.5, range: 36-59), showing an improvement in terms of both pain relief, function and joint mobility. Radiographically neither signs of instability, migration nor tilting were observed. TT custom-implant made by high performance of the 3D-printing technology, system modularity, and patient-specific surgical tools permitted good clinical results and an effective restoration of the biomechanical joint parameters in these complex revision cases.


Spectroscopic and volumetric investigation of cytochrome c unfolding at alkaline pH: characterization of the base-induced unfolded state at 25 degrees C.
We have measured at 25 degrees C the relative specific sound velocity increment, [u], and the partial specific volume, v degrees, of cytochrome c as a function of pH. Our data reveal that the base-induced native to unfolded transition of the protein is accompanied by a volume decrease of 0.014 cm3 g-1 and a compressibility decrease of 3.8 x 10(-6) cm3 g-1 bar-1. These results allow us to conclude that, relative to a fully unfolded conformation, the base-denatured state of cytochrome c has only 70 to 80% of its surface area exposed to the solvent. Recently, we reported a similar result for the acid-denatured state of cytochrome c. Thus, insofar as solvent exposure is concerned, both the base- and the acid-induced unfolded states of cytochrome c retain some order, with 20 to 30% of their surface areas remaining solvent-inaccessible. We discuss the implications of this result in terms of defining potential intermediate states in protein folding pathways.


Outcomes of open versus closed treatment of mandibular subcondylar fractures: a prospective randomized study.
To compare open reduction and internal fixation with closed treatment and maxillomandibular fixation for the management of subcondylar fractures of the mandible. Forty patients with subcondylar fractures of the mandible were evaluated. All fractures were displaced; either angulated between 10 degrees and 35 degrees or the ascending ramus was shortened by more than 2 mm. Clinical and radiographic evaluation was performed 6 months after the trauma. Clinical parameters included mouth opening, protrusion, laterotrusion, deviation on mouth opening, and occlusion. Radiographic parameters included level of the fracture, deviation of the fragment, and shortening of the ascending ramus. Subjective parameters included pain according to a visual analog scale. Nonparametric data were compared for statistical significance with a chi(2) analysis and parametric data with an independent samples t test (P < .05). Correct anatomical position of the fragments was achieved significantly more accurately in the operative group in contrast to the closed treatment group. Regarding mouth opening/lateral excursion/protrusion, significant (P = .00) differences were observed between both groups (open 39.6/12.5/5.9 mm vs closed 33.5/9.8/4.1 mm). The visual analog scoring revealed significant (P = .00) difference with less pain in the operative treatment group (1.1 open vs 5.2 closed). No statistically significant difference was found between the 2 groups for occlusion (P = .86). Both treatment options for condylar fractures of the mandible yielded acceptable results. However, operative treatment was superior in all objective and subjective functional parameters except occlusion.


[Infliximab is effective in difficult-to-control peripheral ulcerative keratitis. A report of three cases].
Peripheral ulcerative keratitis is caused by an inflammatory and destructive process of the perilimbal peripheral cornea. This inflammation is due to immune complex deposition in this region of the cornea and in adjacent vessels. It can be idiopathic, or a manifestation of systemic disease such as rheumatoid arthritis, vasculitis of small vessels associated with ANCA, relapsing polychondritis, systemic lupus erythematosus and Crohn's disease. Its treatment includes the use of high-dose corticosteroids and, in some cases, the concomitant use of immunosuppressants such as methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide or cyclosporine. The use of immunobiological agents can be a strategy in cases of difficult control. The authors describe the treatment of three patients who, after failure with the use of corticosteroids or immunosuppressants, showed good response after the use of infliximab.


Surgeon volume and reoperation risk after midurethral sling surgery.
Emerging research supports that fewer complications occur in patients who undergo surgery by higher surgical volume surgeons. The midurethral sling surgery has been involved in recent warnings and litigation, which further supports a need to understand features that enhance its safety and efficacy. The purpose of this study was to measure the impact of a surgeon's volume on their patient's rate of reoperation after midurethral sling surgery. This was a retrospective cohort study that evaluated all surgeons who performed synthetic mesh midurethral sling surgery for stress urinary incontinence at a large managed care organization with >4.5 million members from 2005-2016. Physicians Current Procedural Terminology and International Classification of Diseases, version 9/10, codes were used to identify the procedures and the reoperations that were performed. The system-wide medical record was queried for demographic and perioperative data. The primary outcome was the overall reoperation rate after midurethral sling surgery. Concentration curves were used to identify the impact of a surgeon's surgical volume on their rate of reoperation. Demographics, characteristics, and reoperation of patients were compared with the use of chi-square test for categoric variables and Wilcoxon rank sum test for continuous variables. Poisson regression models with a robust error variance were used to calculate the unadjusted and the adjusted risk ratios of reoperation with the use of age, body mass index, marital status, race, parity, vaginal estrogen use, sling type, smoking, diabetes mellitus, and menopausal status as covariates. Two hundred twenty-seven surgeons performed 13,404 midurethral sling surgeries over the study period; patients had a mean of 4.4 years of follow up. Higher-volume surgeons (>40 procedures/year, ≥95th percentile) performed 47% of the surgeries in this cohort and had an overall lower rate of reoperation (3.6% vs 4.2%; 95% confidence interval, 0.67-0.94; P=.04) compared with lower-volume surgeons. Higher-volume surgeons had a lower rate of reoperation for surgical failure (2.7% vs 3.6%; 95% confidence interval, 0.55-0.92; P<.01). Rates of reoperation for complications were similar between the 2 groups (1.1% vs 0.9%; 95% confidence interval, 0.82-1.13; P=.32). For patients whose condition required a reoperation secondary to complication, the rates of reoperation for urinary retention (0.9% vs 0.6%; P=.06), mesh exposure (0.2% vs 0.3%; P=.31), hemorrhage/bleeding (0.1% vs 0.0%; P=.11), pain (0.1% vs 0.1%; P=.52), and infection (0.0% vs 0.0%; P=.37) did not differ between higher- and lower-volume surgeons. The risk ratio for reoperation that compared higher- and lower-volume surgeons was 0.83 (95% confidence interval, 0.67-0.98; P=.01) in the adjusted model. Although the reoperation rates were low for both higher- and lower-volume surgeons, higher-volume surgeons had lower overall rates of reoperation after midurethral sling surgery. This effect is seen most dramatically in reoperation for surgical failure, in which patients who have surgery with a higher-volume surgeon are 25% less likely to have postoperative stress urinary incontinence that leads to reoperation.


Cellular behavior as a dynamic field for exploring bone bioengineering: a closer look at cell-biomaterial interface.
Bone is a highly dynamic and specialized tissue, capable of regenerating itself spontaneously when afflicted by minor injuries. Nevertheless, when major lesions occur, it becomes necessary to use biomaterials, which are not only able to endure the cellular proliferation and migration, but also to substitute the original tissue or integrate itself to it. With the life expectancy growth, regenerative medicine has been gaining constant attention in the reconstructive field of dentistry and orthopedy. Focusing on broadening the therapeutic possibilities for the regeneration of injured organs, the development of biomaterials allied with the applicability of gene therapy and bone bioengineering has been receiving vast attention over the recent years. The progress of cellular and molecular biology techniques gave way to new-guided therapy possibilities. Supported by multidisciplinary activities, tissue engineering combines the interaction of physicists, chemists, biologists, engineers, biotechnologist, dentists and physicians with common goals: the search for materials that could promote and lead cell activity. A well-oriented combining of scaffolds, promoting factors, cells, together with gene therapy advances may open new avenues to bone healing in the near future. In this review, our target was to write a report bringing overall concepts on tissue bioengineering, with a special attention to decisive biological parameters for the development of biomaterials, as well as to discuss known intracellular signal transduction as a new manner to be explored within this field, aiming to predict in vitro the quality of the host cell/material and thus contributing with the development of regenerative medicine.


Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations.
Struma ovarii (SO) is a highly specialized ovarian teratoma, consisting of thyroid tissue. Rarely, carcinomas histologically identical to their thyroid counterparts may occur, and are comprehensively defined as malignant struma ovarii (MSO). Their optimal management is controversial, and the molecular profile of the malignant counterpart in the ovary is incompletely known. In this study, the clinicopathological and molecular features of six MSO from different Italian Institutions were analysed, to explore genetic profiles of potential therapeutic interest. The histopathological features and immunoprofile (according to the known markers Galectin-3, HBME1, cytokeratin 19 and CD56) were reviewed. In addition, all cases underwent genetic analysis with a next-generation sequencing (NGS) hot spot cancer panel detecting mutations in 50 genes involved in cancerogenesis. RET/PTC rearrangements and TERT promoter alterations were also evaluated. Papillary carcinoma in all similar to its thyroid counterpart was found in five of six cases, including classical (two tumors) and follicular variant (three tumors) types. The last case was a poorly differentiated carcinoma. An activating gene mutation, was detected in five of six cases, including two NRAS, two BRAF, and one JAK3 oncogene mutations. No alterations were found in the other panel genes, nor in TERT promoter, or in RET chromosomal regions. MSO is a rare condition. Papillary carcinoma is the predominant malignant type, sharing both histomorphological and molecular features of its thyroid counterpart. Interestingly, the single case of poorly differentiated carcinoma displayed a JAK3 mutation. The presence of such driving mutation could be of potential interest in guiding postoperative treatment.


Identification of genes for variable regions of immunoglobulins that recognize sialylated glycans.
We previously reported an antibody (clone ID: FR9, IgM-κ) that recognizes the sialyl oligosaccharide Neu5Acα2,6Galβ1,4GlcNAc as an epitope on glycoproteins and glycolipids. In the present study, we developed an antibody (clone ID: AFR45, IgM-κ) that recognizes Neu5Acα2,3Galβ1,4GlcNAc/Glc as an epitope on glycoproteins and glycolipids and compared the nucleotide and amino acid sequences of the immunoglobulin gene variable regions with those of FR9. The heavy chain variable (VH) regions of FR9 and AFR45 were encoded by different VH gene segments, each of which was composed of a characteristic D gene segment. The major differences between VH genes encoding various antibodies deposited in public databases and FR9 and AFR45 were identified in the D gene segment, indicating that D genes play a critical role in determining the epitope specificity of these antibodies. Surprisingly, although FR9 and AFR45 were obtained independently from different mice immunized with different immunogens, the light chain variable (VL) region nucleotide sequences were identical. The VL gene consisted of Igkv4-57 and Igkj4 gene segments (Igkv4-57j4), the sequences of which were identical to VL genes for a number of antibodies against meningococcal group C capsular polysaccharide deposited in public databases. As this polysaccharide is a sialic acid homopolymer, these results indicate that Igkv4-57j4 encodes a VL common to immunoglobulins that recognize sialylated glycans.


[Research progress in treatment of bone defect with osteomyelitis by using drug-carried bionic nano-bone].
To review the research progress in the treatment of bone defect or osteomyelitis with drug-carried bionic nano-bone so as to offer some theoretic supports and experimental references for those relative researchers. The related literature was reviewed. The research progress in the treatment of bone defect or osteomyelitis with drug-carried bionic nano-bone was analyzed, which included the designing and preparing of drug-carried nano composites, the way of making infected bone defect animal models, and the general steps, test indexes and results. Traumatic osteomyelitis and bone defect were two kinds of disease to difficulty cure in nowadays clinical orthopaedics. The osteomyelitis, especially chronic one was quite troublesome during the treatments. Many researchers made artificial bone with nano-materials and added drugs into them by various ways for the purpose of controlling infection and repairing bone defection simultaneously. But these researches were still at the laboratory phase, lacking the criterions of making relative animal models, and needed to be improved in the way of drug slow-releasing and nano-scaffold producing. The drug-carried bionic nano-bone as a kind of newly emerging replacement material has splendid effects in the treatments of traumatic large area bone defect or osteomyelitis and will have a brilliant future.