The association between the GSTP1 A313G and GSTM1 null/present polymorphisms and the treatment response of the platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients: a meta-analysis.
The relationship between the GSTP1 A313G and GSTM1 null/present polymorphisms and the treatment response (TR) of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients have been extensively investigated by many studies, but the results were inconsistent and inconclusive. The aim of this meta-analysis was to further explore the predictive value of the GSTP1 and GSTM1 polymorphisms by collecting currently available evidence. Relevant studies were searched in PubMed, Embase, and CNKI. Inclusion criteria were NSCLC patients receiving platinum-based treatment, evaluated GSTP1 A313G or GSTM1 null/present polymorphisms, and TR. Odds ratio (OR) with 95 % confidence interval (CI) was calculated to assess the strength of the associations. Subgroup analysis by race was also conducted to explore the source of heterogeneity. A total of nine studies including 961 NSCLC patients were qualified for analysis. We found that GSTM1 null/present but not GSTP1 A313G polymorphism was associated with platinum-based TR (for GSTM1, null vs present: OR = 1.77, 95% CI = 1.19-2.62). When subgroup analysis by race was done, both GSTP1 and GSTM1 polymorphisms were significantly associated with TR in East-Asian patients, but not in Caucasians. In addition, the heterogeneity disappeared in Asian and Caucasian patients when subgroup analysis by race was done. Our study suggested that the GSTP1 A313G and GSTM1 null/present polymorphisms could predict the treatment response of the platinum-based chemotherapy in NSCLC patients, especially in East-Asian patients.


Being bullied and depressive symptoms in Chinese high school students: The role of social support.
The aims of this study were to: 1) examine the relationship between being bullied and depressive symptoms; 2) explore whether the three mentioned sources of social support moderated this association; and 3) examine gender differences in the moderating effects of social support on bullying-associated depressive symptoms among Chinese high school students. A total of 1252 students were selected from three high schools in Zhenping County of Henan Province in China. The results suggest that bullying victimization is significantly associated with depressive symptoms among high school students. In addition, we found that only school-type social support had a moderating effect on depressive symptoms. Those who had been bullied but who had high levels of school support had lower levels of depressive symptoms than those with less school support. However, moderating effects of this support were only found for girls, not for boys. This study empirically supports that programs aimed at boosting social support for students from teachers and classmates, could help protect high school students from depressive symptoms.


Suture Slippage During Anterior Cruciate Ligament Graft Passage Is Significantly Lower Using a Krackow Suture.
To compare the suture slippage on a hamstring tendon graft prepared with a modified finger-trap device (SPEEDTRAP) with one prepared with Krackow stitch during graft passage through the tibial tunnel in ACL reconstruction. Thirty-eight patients underwent anatomic triple-bundle anterior cruciate ligament reconstruction with 2 femoral and 3 tibial tunnels. After semitendinosus tendon was cut in half to make 2 grafts, the free ends of the proximal membranous portion (posterolateral [PL] graft) were prepared together with 2 sutures: (1) one SPEEDTRAP and one Krackow stitch for 20 cases (group A) and (2) double Krackow stitches on both sides for 18 cases (group B). Then, the PL graft was dye-marked at the proximal suture of SPEEDTRAP in group A and Krackow suture in group B and was inserted into the joint via tibial tunnel ahead of the loop side. The distance between the mark on the graft and the proximal suture of SPEEDTRAP or Krackow stitch was measured under arthroscopy after graft fixation at femur. Slippage was defined as 1 mm and more of distance between the mark and the proximal suture. Slippage was observed in 16 cases for SPEEDTRAP and in 2 for Krackow suture in group A, whereas one case showed slippage in group B. The slippage distance was 4.0 ± 2.9 mm for SPEEDTRAP and 0.2 ± 0.5 mm for Krackow stitch in group A (P < .001), whereas it was 0.1 ± 0.2 mm for double Krackow stitch in group B, showing a significant difference from SPEEDTRAP suture (P < .001). At the time of PL graft passage through the tibial tunnel in anterior cruciate ligament reconstruction, there was significantly less slippage observed with the Krackow stitch compared with the SPEEDTRAP stitch. Level IV, therapeutic case series.


Efficacy of a novel device for cryoprevention of oral mucositis: a randomized, blinded, multicenter, parallel group, phase 3 trial.
Cryoprevention (CP) using ice (IC) is an effective strategy to prevent chemotherapy-induced oral mucositis (OM). However, the use of IC may cause adverse reactions and requires water of safe quality to minimize risk of serious infections. This randomized, blinded, parallel group, phase 3 trial was conducted in five Scandinavian centers. Eligible patients were diagnosed with multiple myeloma or lymphoma, scheduled to receive conditioning with high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation (ASCT). Patients were assigned to cooling with IC or a novel intraoral cooling device (ICD). The primary outcome was the highest OM score during the study period, expressed as peak value on the Oral Mucositis Assessment Scale (OMAS-total). When the entire study population (n = 172) was analyzed for peak OMAS-total, the two cooling methods were equally effective. However, when the lymphoma group was analyzed separately, the ICD significantly reduced the peak OMAS-total score to a greater extent compared to IC (x̄ ± SD; 1.77 ± 1.59 vs. 3.08 ± 1.50; p = 0.047). Combined with existing evidence, the results of the present trial confirm that CP is an effective method to prevent OM. ClinicalTrials.gov. NCT03203733.


Ergodicity-breaking transition and high-frequency response in a simple free-energy landscape.
We present a simple dynamical model described by a Langevin equation in a piecewise parabolic free-energy landscape, modulated by a temperature-dependent overall curvature. The zero-curvature point marks a transition to a phase with broken ergodicity. The frequency-dependent response near this transition is reminiscent of observations near the glass transition.


Infliximab continuation rates in patients with rheumatoid arthritis in everyday practice.
Infliximab is a major breakthrough in the management of rheumatoid arthritis (RA). We evaluated infliximab continuation rates and reasons for discontinuation in patients with RA. We studied patients with RA started on infliximab at any time between March 2000 and December 2002, under the conditions of everyday practice (as opposed to clinical trial settings), as recommended by the French marketing license (3 mg/kg as an intravenous infusion at weeks 0, 2, and 6 then at 8-week intervals). The number of infliximab infusions, side effects, and nonresponse rates was recorded. The Kaplan-Meier method was used to evaluate treatment continuation. Reasons for discontinuation were studied. We included 41 patients, with a mean age of 54 years, a mean RA duration of 9 years, and a mean of three previous disease-modifying antirheumatic drug treatments. The total number of infliximab infusions was 461 with a mean of 10.8 per patient and a mean follow-up under treatment of 15.3 months. The proportions of patients still on infliximab were 82%, 74%, and 67% after 6, 12, and 24 months, respectively. The main reasons for discontinuation were escape phenomenon (n = 6, 42.8% of discontinuations) and allergy (n = 3); in one case each, the reason was primary ineffectiveness, severe infection, plans to start a pregnancy, poor compliance, and unavailability for follow-up. There were 59 recorded episodes of side effects, with a profile similar to that in the literature and in postmarketing databases. The infliximab continuation rate in everyday practice in patients with RA (67% after 2 years) was consistent with published data and with the results of controlled trials.


Fatal granulomatous amebic encephalitis initially presenting with a cutaneous lesion.
We present a case of a 66-year-old man with a cutaneous Balamuthia mandrillaris lesion that progressed to fatal granulomatous amoebic encephalitis. We provide a summary of Australian cases and describe the clinical features and approach to diagnosing this rare but devastating condition, including the importance of PCR for diagnosis.


Effects of soman and sarin on high affinity choline uptake by rat brain synaptosomes.
Synaptosomes were incubated at various time intervals following injection of 120 micrograms/kg SC of soman or sarin or with various concentrations (10(-8) to 10(-2) M) of soman or sarin in vitro. Total cholinesterase (ChE) activities in each brain region were also measured. Following soman injection, sodium-dependent, high affinity choline uptake (SDHACU) was decreased from 1 to 4 hr in the cortex and from 1 to 2 hr in the hippocampus, but increased from 2 to 24 hr in the striatum. Similarly, following sarin injection SDHACU was decreased at 0.5 hr in the cortex and from 1 to 4 hr in the hippocampus, but increased at 1 hr in the striatum. Injection of soman severely inhibited (83-99%) total ChE activity in the cortex, hippocampus and striatum from 1 to 24 hr. In contrast, sarin did not severely inhibit ChE activity in these regions and maximal inhibition (40-60%) did not occur until 24 hr after injection. With both compounds, by 168 hr ChE activity in all regions had partially recovered. Incubation of synaptosomes with soman or sarin in vitro at concentrations below 10(-4) M did not affect SDHACU in any of the brain regions. These data demonstrated that acute soman and sarin injection produced similar effects upon SDHACU in different brain regions, although the time-course of these effects was different for the two compounds. These effects were probably neither due to a direct action of these compounds on the uptake process nor dependent on ChE inhibition.


A potent allele marker related to low bull conception rate in Japanese Black bulls.
Over the years, there has been considerable variation in the bull conception rate (BCR) of Japanese Black cattle; moreover, several Japanese Black bulls with a low BCR of ≤10% have been identified. However, the alleles responsible for the low BCR are not determined yet. Therefore, in this study, we aimed to identify single-nucleotide polymorphisms (SNPs) for predicting low BCR. To this end, the genome of Japanese Black bulls was comprehensively examined by a genome-wide association study with whole-exome sequencing (WES), and the effect of the identified marker regions on BCR was determined. The WES analysis of six sub-fertile bulls with a BCR of ≤10% and 73 normal bulls with a BCR of ≥40% identified a homozygous genotype for low BCR in Bos taurus autosome 5 in the region between 116.2 and 117.9 Mb. The g.116408653G > A SNP in this region had the most significant effect on the BCR (P-value = 1.0 × 10-23), and the GG (55.4 ± 11.2%) and AG (54.4 ± 9.4%) genotypes in the SNP had a higher phenotype than the AA (9.5 ± 6.1%) genotype for the BCR. The mixed model analysis revealed that g.116408653G > A was related to approximately 43% of the total genetic variance. In conclusion, the AA genotype of g.116408653G > A is a useful index for identifying sub-fertile Japanese Black bulls. Some positive and negative effects of SNP on the BCR were presumed to identify the causative mutations, which can help evaluate bull fertility.


Is nevirapine dose-escalation appropriate in young, African, HIV-infected children?
Young children metabolize nevirapine faster than older children/adults. We evaluated nevirapine pharmacokinetics with or without dose-escalation in Zambian, HIV-infected infants/children and its relationship with safety/efficacy. A retrospective pharmacokinetic substudy of the CHAPAS-1 trial. HIV-infected, Zambian children were randomized to initiate antiretroviral therapy (ART) with full-dose twice-daily nevirapine versus 2-week nevirapine dose-escalation. Samples taken 3-4 h postmorning-dose 2 weeks after nevirapine initiation were assayed for nevirapine levels. Viral load was measured on available samples at weeks 4 and 48; adverse events were prospectively reported. Of 162 (77%) children with week-2 samples, 79 (49%) were randomized to nevirapine dose-escalation. At ART initiation, median [interquartile range (IQR)] age, weight and CD4% were 5.2 (1.5-8.7) years, 13.0 (8.1-19.0) kg and 13 (8-18)%, respectively; 81 (50%) were male. With full dose, few children aged less than 2 years (3/23, 13%) or more than 2 years (4/60, 7%) had subtherapeutic nevirapine levels (defined as <3.0 mg/l), but with dose-escalation, seven out of 22 (32%) aged less than 2 years versus seven out of 57 (12%) more than 2 years had subtherapeutic nevirapine levels (P=0.05). There was no difference between week-2 nevirapine levels in those with viral load more than 250 versus less than 250 copies/ml at week 4 (P=0.97) or week 48 (P=0.40). Eleven out of 162 children had grade 1/2 rash; all were more than 2 years of age (P=0.04), and 10 were randomized to full dose. Subtherapeutic nevirapine levels 3-4 h postdose were more frequent in young children on dose-escalation. Younger children were at lower risk for rash. To simplify ART initiation and reduce the risk of suboptimal dosing, full-dose nevirapine at ART initiation should be considered for African HIV-infected children less than 2 years of age.


Crystal structure of manganese superoxide dismutase from Bacillus stearothermophilus at 2.4 A resolution.
The crystal structure of manganese superoxide dismutase (MnSOD) from Bacillus stearothermophilus has been solved at 2.4 A resolution by a combination of multiple isomorphous replacement and molecular replacement (1 A = 0.1 nm). The structure has been refined to a conventional R-factor for all 16,560 unique reflections at 2.4 A of 0.26, and the 2Fo-Fc density maps show features more consistent with the known amino acid sequence of MnSOD from B. stearothermophilus than with the starting model, the MnSOD from Thermus thermophilus. The molecule is a dimer of identical subunits, each with 203 amino acid residues. The polypeptide chain of the monomer is organized into two domains, one of which has an "all-alpha" structure and the other an "alpha/beta" structure, with the manganese ion bound between them. The ion is co-ordinated by three histidine residues, 26, 81 and 167, and one aspartic acid residue, 173, in a tetrahedral arrangement strongly distorted towards trigonal pyramidal. We anticipate that Tyr34, whose hydroxyl group is only 5 A from the metal, is involved in the catalytic reaction. The active site is particularly rich in aromatic amino acid residues. As in the Cu/ZnSOD there are indications that MnSOD provides electrostatic guidance to the substrate entering the active site.


The role of a salt marsh plant on trace metal bioavailability in sediments. Estimation by different chemical approaches.
The presence or absence of vegetation can condition sediment characteristics. The main aim of this work was to investigate the influence of the sea rush Juncus maritimus on metal (Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn) availability to organisms living on or in estuarine sediments, from Douro River (NW Portugal), by comparing the characteristics and chemical behaviour of rhizosediments (collected within the plant assemblage) and those of sediment (collected around the plant). In order to evaluate whether and how sediment characteristics condition the role of plants on metal availability, sandy and muddy sediments colonised by J. maritimus were studied in parallel. Metal availability was estimated by enzymatic digestion with pepsin (ED), which may provide an estimate of metal availability to organisms living at estuarine sediments. Nevertheless, since no consensus exists yet on the most suitable methodologies to estimate metal bioavailability in sediments, two more conventional approaches, BCR sequential extraction (SE) and AVS/ SEM model, were also used, in parallel, and the information these approaches provided was compared with that provided by ED. Total-recoverable metal contents were determined by atomic absorption spectrophotometry after sediment digestion using a high-pressure microwave system. Plants could concentrate metals around its roots and rhizomes. In addition, they were capable of oxidizing (release of oxygen by the roots) the anaerobic medium surrounding their roots in muddy sediment (reducing AVS). As sulphide oxidation renders metals (Cd, Cu, Ni, Pb and Zn) into more soluble forms, according to the AVS/SEM model, metals from muddy sites would be more available in rhizosediment than in sediment. The SE approach led to a similar conclusion. Nevertheless, the results provided by ED pointed at opposite conclusion, particularly for Cd and Zn, indicating less availability at rhizosediments than in the surrounding sediment. ED results were interpreted as a consequence of an enrichment of the rhizosediment in organic ligands exuded by the roots or liberated by dead plants. The effect of complexation of metals by organic compounds, which ED could not decompose/dissolve, seemed to overcome that caused by sediment oxidation. In general, a comparison of the informa tion about metal availability by ED, SE, AVS/SEM, showed that it did not always match and in few cases it was even contradictory. Therefore, a thorough evaluation of the metal availability in sediments requires a combination of different chemical approaches, so as to take into consideration differences in ways of organism exposure (interstitial water and/or ingestion of sediment particles).


Preparation and application of functionalized nano drug carriers.
Targeting at category memory characteristics and preparation methods of functionalized nano drugs, preparation technology of functionalized nano drug carriers is studied, and then important role of functionalized nano drug carrier in preparation of medicine is studied. Carry out the relevant literature search with computer, change limited language in the paper to Chinese and necessarily remove repetitive studies. After first review of 1260 retrieved literature, it can be found that nano drug is with accurate quantity, relatively good targeting, specificity and absorbency. Necessary research of nano drug carriers can prevent and treat disease to a certain extent. Preparation of functionalized nanocarrier is simple and convenient, which can improve frequency of use of nano preparation technology and provide better development space for medical use. Therefore, nanocarriers should be combined with drugs with relatively strong specificity in clinics, in order to be able to conduct effective research on nanometer intelligent drug, effectively promote long-term development of nano biotechnology, and then provide favorable, reliable basis for clinical diagnosis and treatment.


One-Pot Synthesis of Styrene Derivatives from Allyl Silanes via B(C6F5)3-Catalyzed Isomerization-Hiyama Coupling.
Herein, we report a one-pot synthesis of styrene derivatives via a novel B(C6F5)3-catalyzed E-selective isomerization of readily accessible allyl silanes and subsequent Hiyama coupling of the versatile alkenyl silane intermediates. This one-pot, two-step approach enables access to a broad range of styrene derivatives, including those containing Lewis basic functional groups, that cannot be accessed via the previously developed B(C6F5)3-catalyzed isomerization of allyl benzenes.


Microstructural investigation to the controlled release kinetics of monolith osmotic pump tablets via synchrotron radiation X-ray microtomography.
Tomographic imaging techniques are attractive tools for the visualization of the internal structural characteristics of pharmaceutical solid dosage forms. In this paper, the internal structure of the tablet core for a monolith osmotic drug delivery system, felodipine sustained-release tablet, was visualized via synchrotron radiation X-ray computed microtomography during the drug release process. The surface areas and three dimensional parameters of the tablet core were calculated based on the three dimensional reconstruction of the images. At different stages of the drug release process, the surface morphology, the hydration, the swelling, and the structure changing of the tablet, were visualized from the two dimensional monochrome X-ray images. The three dimensional volumes of the remaining tablet core correlated well with the percentages of felodipine (R=0.9988). Also, the three dimensional surface area almost unchanged during the drug release process, which clearly demonstrated the intrinsic drug release mechanism of the osmotic drug delivery system. In conclusion, the synchrotron radiation X-ray computed microtomography, with rapid acquisition, high intensity and micro-scale spatial resolution, was found to be a useful tool for the quantitative elucidation of the intrinsic drug release kinetics and the three dimensional parameters such as surface areas of the remained core obtained by the synchrotron radiation. Thus, X-ray computed microtomography can be considered as a new and complimentary analytical tool to standard compendial pharmaceutical tests for quality control of osmotic drug delivery systems.


Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis.
The prognostic value of FoxP3(+) regulatory T cells (Tregs) in cancer remains controversial. We did a meta-analysis to assess the prognostic effect of FoxP3(+) Treg across different types of cancer and to investigate factors associated with variations in this effect. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched to identify eligible studies. In total, we analyzed 76 articles encompassing 17 types of cancer, and including 15,512 cancer cases. The overall pooled analysis including all types of cancer suggested FoxP3(+)Tregs had a significant negative effect on overall survival (OS) (OR 1.46, P < 0.001), but the prognostic effect varied greatly according to tumor site. High FoxP3(+) Tregs infiltration was significantly associated with shorter OS in the majority of solid tumors studied, including cervical, renal, melanomas, and breast cancers, et al; whereas, FoxP3(+) Tregs were associated with improved survival in colorectal, head and neck, and oesophageal cancers. The stratified analysis suggested the molecular subtype and tumor stage significantly influenced the prognostic value of FoxP3(+) Tregs in certain types of cancer. In conclusion, our meta-analysis suggests that the prognostic role of FoxP3(+) Tregs was highly influenced by tumor site, and was also correlated with the molecular subtype and tumor stage.


A Real-World Evaluation of the Long-Term Safety and Efficacy of Infliximab in the Treatment Moderate-to-Severe Psoriasis.
Psoriasis is a chronic immune-mediated inflammatory skin disease that occurs in 2.5-3.5% of the general population. Infliximab (INF), a TNF-α inhibitor biologic agent, is a long-standing efficacious treatment for psoriasis; however, not all patients sustain a long-term response (LTR) because of a number of factors including antibody production. There is a paucity of studies assessing infliximab efficacy over a period ≥ 5 years. A retrospective cohort chart review of our clinic patients who had undergone ≥ 5 years of treatment with infliximab for chronic plaque psoriasis was performed. The following variables were recorded and analyzed with the Fisher exact test: age, sex, body mass index ([BMI]; normal weight [NW], overweight [OW], obese [OB]), changes in infliximab strength (dose or frequency), concomitant systemic therapy, and side effects. Clinical improvement was assessed by comparing the total body surface area (tBSA) affected by psoriasis before and after treatment. There was a significant difference in likelihood of achieving LTR between the NW, OW and OB groups (p = 0.044). Non-normal-weight patients (OW + OB) were significantly more likely to achieve and sustain LTR than NW patients (OR 9.07, p = 0.020). There were no other significant associations for the other evaluated variables. Patients who began treatment with infliximab before 2009 (prior to the use of the clinic's electronic medical record) were excluded. The Psoriasis Area and Severity Index (PASI) was not available for this study. Surprisingly, patients who are overweight or obese are more likely to obtain long-term clinical benefit in their psoriasis symptoms with infliximab therapy than patients who are normal weight.


Anti-biofilm activity of caffeine against uropathogenic E. coli is mediated by curli biogenesis.
Biofilms are assemblages of sessile microorganisms that form an extracellular matrix around themselves and mediate attachment to surfaces. The major component of the extracellular matrix of Uropathogenic E. coli and other Enterobacteriaceae are curli fibers, making biofilms robust and resistant to antimicrobials. It is therefore imperative to screen antibiofilm compounds that can impair biofilm formation. In the present study, we investigated the curli-dependent antibiofilm activity of caffeine against UPEC strain CFT073 and commensal strain E. coli K-12MG1655.Caffeine significantly reduced the biofilm formation of both UPEC and E. coli K-12 by 86.58% and 91.80% respectively at 48 mM caffeine as determined by Crystal Violet assay. These results were further confirmed by fluorescence microscopy and Scanning Electron Microscope (SEM). Caffeine significantly reduced the cytotoxicity and survivability of UPEC. Molecular docking analysis revealed a strong interaction between caffeine and curli regulator protein (Csg D) of E. coli. The qRT-PCR data also showed significant downregulation in the expression of CsgBA and the CsgDEFG operon at both 24 mM and 48 mM caffeine. The findings revealed that caffeine could inhibit E. coli biofilm formation by regulating curli assembly and thus may be used as an alternative therapeutic strategy for the treatment of chronic E. coli biofilm-related infections.


Complementary medicine in cancer care: adding a therapy dog to the team.
Animal-assisted therapy, including visits from certified therapy dogs, offer a valuable and often underutilized resource for addressing unmet needs in cancer patients. Prospective research studies have documented symptomatic benefits for reducing pain, psychological distress, and fatigue in a variety of patient populations, including cancer patients. Utilizing consistent policies minimizes patient risk and infection control concerns associated with animal visits.


Modulation of rat pancreatic amylase secretion and muscarinic receptor populations by chronic bethanechol treatment.
F8P6effect of a chronic bethanechol treatment (12 mg X kg-1 X day-1 i.p., for 14 days) was investigated on pancreatic amylase secretion and muscarinic cholinergic receptors in the rat. Dispersed pancreatic acini were used to evaluate enzyme secretion and binding of [3H]N-methylscopolamine, [( 3H]NMS). The bethanechol treatment caused a 4 fold decrease in sensitivity of the pancreas for amylase release in the presence of carbamylcholine, the EC50 being shifted from 0.69 microM to 2.9 microM. Receptor concentration was reduced by 42%, from 3360 to 1930 fmol/mg DNA. The equilibrium dissociation constant (KD) of the receptors for the ligand remained unchanged at 0.17 nM. Binding analysis of carbachol on the muscarinic receptors in terms of two classes of binding sites indicated that the shift in the dose-response curve of amylase secretion was accompanied by modifications to the high and low affinity forms. The maximal number of high affinity sites remained the same while their affinity was greatly decreased from 0.24 to 6.1 microM. The low affinity form showed a moderate decrease in affinity from 34 to 150 microM but a large drop in their numbers from 2620 to 890 fmol/mg DNA. These results suggest that the shift in the amylase dose-response curve to carbamylcholine, noted following bethanechol treatment in vivo, could be coupled with the observed change in affinity of the two agonist forms of muscarinic receptor in the pancreas. However, gradual occupancy or formation of the high affinity form of muscarinic receptors by cholinergic agonist corresponds well with the gradual stimulation of amylase release.


Nanosheets of MoSe2@M (M = Pd and Rh) function as widespread pH tolerable hydrogen evolution catalyst.
In this present study we have developed method for the synthesis of MoSe2 nanosheets following a simple hydrothermal technique. Palladium (Pd) and rhodium (Rh) nanoparticles were decorated on the surface of MoSe2 following a simple wet-chemical route. Pd and Rh nanoparticles decorated MoSe2 were applied for hydrogen evolution reaction (HER) in different pH conditions like acidic (0.5 M H2SO4), neutral (pH-7 buffer) and in alkaline (1 M KOH) medium and 3.5 wt% of saline water. Pd and Rh decorated MoSe2 show efficient activity towards HER irrespective of the applied electrolyte. In 0.5 M H2SO4, MoSe2 can produce 10 mA/cm2 current density with applied potential of -0.256 V vs. RHE. Rh decorated MoSe2 shows more shift in the onset potential. Upon applied potential of -0.192 V vs. RHE, MoSe2/Rh can produce 10 mA/cm2 current density. MoSe2/Rh is electrocatalytically more active than MoSe2/Pd which is established from the calculated electrochemically active surface area (ECSA) value. Significantly lower (47 mV/decade) Tafel value is observed for MoSe2/Rh in 0.5 M H2SO4 which indicates the superior activity. MoSe2/Rh is more stable in neutral and alkaline medium compared to acidic medium and it can retain its own activity even after continuous 12 h reaction.


0.79 ppm scale-factor nonlinearity whole-angle microshell gyroscope realized by real-time calibration of capacitive displacement detection.
Whole-angle gyroscopes have broad prospects for development with inherent advantages of excellent scale factor, wide bandwidth and measurement range, which are restrictions on rate gyroscopes. Previous studies on the whole-angle mode are based mostly on the linear model of Lynch, and the essential nonlinearity of capacitive displacement detection is always neglected, which has significant negative effects on the performance. In this paper, a novel real-time calibration method of capacitive displacement detection is proposed to eliminate these nonlinear effects. This novel method innovatively takes advantage of the relationship between the first and third harmonic components of detective signals for calibration. Based on this method, the real-time calibration of capacitive displacement detection is achieved and solves the problems of traditional methods, which are usually related to the vibration amplitude, environmental variations and other factors. Furthermore, this novel calibration method is embedded into a whole-angle control system to restore the linear capacitive response in real time and then combined with a microshell resonator for the first time to exploit the enormous potential of an ultrahigh Q factor and symmetric structure. The effectiveness is proven because the angle drift is reduced significantly to improve the scale-factor nonlinearity by 14 times to 0.79 ppm with 0.0673°/h bias instability and a 0.001°/s rate threshold, which is the best reported performance of the MEMS whole-angle gyroscope thus far. More importantly, this novel calibration method can be applied for all kinds of resonators with the requirement of a linear capacitive response even under a large resonant amplitude.


Association between ambient fine particulate matter and adult outpatient visits for rheumatoid arthritis in Beijing, China.
The association between fine particulate matter (PM2.5) and rheumatoid arthritis (RA) is currently unclear, especially in Beijing, a city with severe air pollution. Our study aimed to explore the relationship between short-term outdoor exposure to PM2.5 and RA outpatient visits using a time-series analysis in Beijing. We used the Beijing's Medical Claims for Employees database to identify patients with RA in 2010-2012. A generalized additive model with a Poisson link was used to estimate the percentage change in RA outpatient visits after the PM2.5 concentration increased by 10 μg/m3. From January 1, 2010, to June 30, 2012, a total of 541,061 RA outpatient visits were identified. During the study period, the average daily (standard deviation) concentration of PM2.5 was 99.5 (75.3) µg/m3. A 10 µg/m3 increase in PM2.5 concentration was correlated with a 0.21% (95% CI, 0.18-0.23%) increase in outpatient visits for RA on the same day. A significant association for the cumulative effect of PM2.5 was found, and the largest significant association was observed for a lag of 0-3 days (0.26%; 95% CI, 0.23-0.29%). Stratified analyses revealed that females (0.29%, 95% CI: 0.26-0.33%) and 18-65 years old patients (0.29%, 95% CI: 0.25-0.32%) were most susceptible to the effects of PM2.5 exposure. The current findings showed that short-term exposure to PM2.5 was followed by an increase in the number of outpatient visits for RA in Beijing. Future studies should investigate the mechanisms underlying this association.


Use of ultrasound-assisted arthroscopy in rheumatology: an experience in 11 patients with different rheumatic diseases.
The 'real time' capability of ultrasound (US) allows dynamic assessment of joint and tendon movements, which can often aid in the detection of structural abnormalities. The simultaneous use of arthroscopy (AS) and US is therefore a logical progression. Here the results of a series of 11 patients with different rheumatic diseases in whom a combined use of US and AS was adopted are reported.


Development of cyclic peptides with potent in vivo osteogenic activity through RaPID-based affinity maturation.
Osteoporosis is caused by a disequilibrium between bone resorption and bone formation. Therapeutics for osteoporosis can be divided into antiresorptives that suppress bone resorption and anabolics which increase bone formation. Currently, the only anabolic treatment options are parathyroid hormone mimetics or an anti-sclerostin monoclonal antibody. With the current global increases in demographics at risk for osteoporosis, development of therapeutics that elicit anabolic activity through alternative mechanisms is imperative. Blockade of the PlexinB1 and Semaphorin4D interaction on osteoblasts has been shown to be a promising mechanism to increase bone formation. Here we report the discovery of cyclic peptides by a novel RaPID (Random nonstandard Peptides Integrated Discovery) system-based affinity maturation methodology that generated the peptide PB1m6A9 which binds with high affinity to both human and mouse PlexinB1. The chemically dimerized peptide, PB1d6A9, showed potent inhibition of PlexinB1 signaling in mouse primary osteoblast cultures, resulting in significant enhancement of bone formation even compared to non-Semaphorin4D-treated controls. This high anabolic activity was also observed in vivo when the lipidated PB1d6A9 (PB1d6A9-Pal) was intravenously administered once weekly to ovariectomized mice, leading to complete rescue of bone loss. The potent osteogenic properties of this peptide shows great promise as an addition to the current anabolic treatment options for bone diseases such as osteoporosis.


Agreement between self-reported data on medicine use and prescription records vary according to method of analysis and therapeutic group.
This study compared national self-reported data on medicine use and national prescription records at the individual level. Data from the nationally representative Danish health survey conducted in 2000 (n=16,688) were linked at the individual level to national prescription records covering 1999-2000. Kappa statistics and 95% confidence intervals were calculated. Applying the legend time method to medicine groups used mainly on a chronic basis revealed good to very good agreement between the two data sources, whereas medicines used as needed showed fair to moderate agreement. When a fixed-time window was applied for analysis, agreement was unchanged for medicines used mainly on a chronic basis, whereas agreement increased somewhat compared to the legend time method when analyzing medicines used as needed. Agreement between national self-reported data and national prescription records differed according to method of analysis and therapeutic group. A fixed-time window is an appropriate method of analysis for most therapeutic groups.


Intracellular pH regulation in cecal epithelial cells from the chick.
Intracellular pH (pHi) regulation has been investigated in cells isolated from the proximal ceca of the chicken. pHi was measured with the pH-sensitive dye, 2',7'-bis(carboxyethyl)-5 (6)-carboxyfluorescein in nominally HCO(3-)-free solutions. Under resting conditions the pHi was 7.08. Removal of extracellular Na+ decreased pHi by approx. 0.24 pH units and the subsequent addition of Na+ increased pHi towards the control value. This Na(+)-dependent pHi recovery was inhibited by 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Following an intracellular acidification, by abrupt withdrawal of NH4Cl, pHi alkalinized in the nominally absence of Na+. Rotenone, N-ethylmaleimide, N,N'-dicyclohexylcarbodiimide, 4-chloro-7-nitrobenz-2-oxa-1,3-diazole, iodoacetic acid and SCH 28080 inhibited the Na(+)-independent pHi recovery rate by 82, 82, 67, 74, 77 and 50% respectively. Bafilomycin A1 was without effect. Na(+)-independent cell alkalization was stimulated by external K+. In the presence of N-ethylmaleimide addition of Na+ induced a rapid pHi recovery. The initial rate of this recovery exhibited first-order dependence on Na+ concentration and it was inhibited by EIPA. The initial rate of Na(+)-dependent cell alkalization increased with a Hill coefficient greater than one when pHi was reduced from 7.2 to 6.2. The 'set point' for the exchanger is approx. 7.5. These studies demonstrate that in cecal epithelial cells exist at least two mechanisms for proton secretion: a Na(+)-H+ exchanger and a Na(+)-independent proton transport system.


Cardiac findings of reactive arthritis: an observational echocardiographic study.
The aim of this study was to assess echocardiographically the occurrence of cardiac abnormalities in patients with acute reactive arthritis (ReA). Eighteen consecutive adult patients with acute ReA were studied by the use of two-dimensionally guided M-mode and Doppler echocardiography. Aortic or mitral regurgitation were both detected in one of the patients. Mild to moderate left ventricular dilatation was observed in five patients, in four of whom the duration of acute ReA was over 6 months. In four patients, the ratio of peak early and peak late transmitral filling velocities was decreased. No patient had echocardiographic signs of myocarditis or pericardial effusion. In conclusion, no major structural cardiac alterations were detected. Mild valvular disease or mild to moderate left ventricular dilatation was observed in a quarter of the patients. Echocardiographic evaluation may be warranted if the acute ReA persists or has a prolonged course but is not recommended for routine use.


Correction: Core-shell Zn₂GeO₄ nanorods and their size-dependent photoluminescence properties.
Correction for 'Core-shell Zn2GeO4 nanorods and their size-dependent photoluminescence properties' by Songping Wu et al., Nanoscale, 2013, 5, 12335-12341.


The accuracy of electrocardiographic Q waves for the detection of prior myocardial infarction as assessed by a novel standard of reference.
The electrocardiogram (ECG) is valuable for the identification of prior myocardial infarction (MI) in individuals participating in epidemiologic studies or undergoing screening examinations. Although the Minnesota Code, a set of criteria for the interpretation of ECGs in such situations, is commonly used to identify MI in these settings, its accuracy is incompletely understood. We sought to test the accuracy of the Minnesota Code Q and QS criteria for MI against a new standard of reference, the presence of a perfusion defect on a resting myocardial scintigraphic image. The resting myocardial scintigrams of all patients studied in our nuclear cardiology laboratory during 7 consecutive months were screened for the presence of perfusion defects. For each patient with such a defect, two individuals examined on the same day, who had no perfusion defect, were selected as controls. Electrocardiograms recorded within 30 days of the scintigraphy were read blindly by two of the authors using the Minnesota Code criteria for Q or QS waves indicative of MI. For 214 patients selected on the basis of their scintigraphic findings, a satisfactory ECG recorded within a month of the scintigraphy was also available. The overall sensitivity of the Q or QS criteria was 0.58 and the specificity was 0.75. As might be expected when only the most stringent criteria were applied, sensitivity was least and the specificity best. As in previous studies, in which necropsy material served as the standard of reference, sensitivity of the Q and QS criteria contained in the Minnesota Code is relatively modest and specificity is reasonable but not outstanding.


The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis.
The heat shock protein 90 co-chaperone p23 has recently been shown to be up-regulated in cancer cells and down-regulated in atheroschlerotic plaques. We found that p23 is degraded during apoptosis induced by several stimuli, including Fas and TNFalpha-receptor activation as well as staurosporine treatment. Caspase inhibition protected p23 from degradation in several cell lines. In addition, recombinant caspase-3 and 8 cleaved p23 at Asp 142 generating a degradation product of 18 kDa as seen in apoptotic cells. Truncated p23 is further degraded in a proteasome dependent process during apoptosis. Furthermore, we found that the anti-aggregating activity of truncated p23 was reduced compared to full length p23 indicating that caspase mediated p23 degradation contributes to protein destabilisation in apoptosis.


Design and synthesis of a pyridone-based phosphotyrosine mimetic.
A novel pyridone-based tyrosine analog, 6, has been designed to mimic the binding interaction of SH2 domains with phosphotyrosine (pTyr) containing peptides. Synthesis of 6 features a key Pd catalyzed coupling of beta-iodoalanine with phosphonomethyl 4-pyridone triflate.


Receptor-mediated transport and deposition of complement component C3 into developing chicken oocytes.
Immunological resistance of the chick embryo is dependent upon IgG present in the yolk of the layed egg. Here we show that complement factor 3 (C3), a key component of the humoral complement system, is a yolk component of chicken eggs. C3 is transported into oocytes by LR8-mediated endocytosis. LR8 also binds and transports other major yolk components such as vitellogenin, very-low-density lipoprotein, and alpha(2)-macroglobulin. Expression studies of LR8 during chicken development and oocyte maturation, in combination with studies on the uptake of individual yolk components, suggest the following model for oocyte maturation in the chicken: all oocytes present in the ovary contain high levels of LR8 mRNA and protein long before the onset of oocyte maturation. Selected oocytes gain access to yolk precursors, and LR8 binds, internalizes, and deposits the major yolk components in the ratio of their relative abundance in the accessible pool.


Cloning of resistance gene analogs located on the alien chromosome in an addition line of wheat-Thinopyrum intermedium.
Homology-based gene/gene-analog cloning method has been extensively applied in isolation of RGAs (resistance gene analogs) in various plant species. However, serious interference of sequences on homoeologous chromosomes in polyploidy species usually occurred when cloning RGAs in a specific chromosome. In this research, the techniques of chromosome microdissection combined with homology-based cloning were used to clone RGAs from a specific chromosome of Wheat-Thinopyrum alien addition line TAi-27, which was derived from common wheat and Thinopyrum intermedium with a pair of chromosomes from Th. intermedium. The alien chromosomes carry genes for resistance to BYDV. The alien chromosome in TAi-27 was isolated by a glass needle and digested with proteinase K. The DNA of the alien chromosome was amplified by two rounds of Sau3A linker adaptor-mediated PCR. RGAs were amplified by PCR with the degenerated primers designed based on conserved domains of published resistance genes (R genes) by using the alien chromosome DNA, genomic DNA and cDNA of Th. intermedium, TAi-27 and 3B-2 (a parent of TAi-27) as templates. A total of seven RGAs were obtained and sequenced. Of which, a constitutively expressed single-copy NBS-LRR type RGA ACR 3 was amplified from the dissected alien chromosome of TAi-27, TcDR 2 and TcDR 3 were from cDNA of Th. intermedium, AcDR 3 was from cDNA of TAi-27, FcDR 2 was from cDNA of 3B-2, AR 2 was from genomic DNA of TAi-27 and TR 2 was from genomic DNA of Th. intermedium. Sequence homology analyses showed that the above RGAs were highly homologous with known resistance genes or resistance gene analogs and belonged to NBS-LRR type of R genes. ACR 3 was recovered by PCR from genomic DNA and cDNA of Th. intermedium and TAi-27, but not from 3B-2. Southern hybridization using the digested genomic DNA of Th. intermedium, TAi-27 and 3B-2 as the template and ACR 3 as the probe showed that there is only one copy of ACR 3 in the genome of Th. intermedium and TAi-27, but it is absent in 3B-2. The ACR 3 could be used as a specific probe of the R gene on the alien chromosome of TAi-27. Results of Northern hybridization suggested that ACR 3 was constitutively expressed in Th. intermedium and TAi-27, but not 3B-2, and expressed higher in leaves than in roots. This research demonstrated a new way to clone RGAs located on a specific chromosome. The information reported here should be useful to understand the resistance mechanism of, and to clone resistant genes from, the alien chromosome in TAi-27.


Assessing dairy calf response to long-distance transportation using conditioned place aversion.
Surplus neonatal dairy calves are routinely transported long distances from the dairy farm of birth to calf raisers. Most of the research assessing the effect of transportation on young calves has focused on physiology and health, without considering calf affective states. The aim of this study was to assess the affective response of young male dairy calves to transportation using conditioned place aversion (CPA) testing. Three bouts of transportation exposed dairy calves (n = 95) to transportation for 6 (n = 31), 12 (n = 32), or 16 h (n = 30). During transportation, the trailer interior was made visually distinct using blue horizontal (n = 2 groups) or red vertical (n = 1 group) stripes. Distinct color and pattern combinations were used to create a visual association with transportation. A subset of calves (6 h = 14; 12 h = 14; 16 h = 14) were selected for CPA testing if they were ≥7 and <28 d of age at the time of testing after transport. A group of sham calves that were not transported (n = 13) and were ≥7 and <28 d of age at the time of testing also were enrolled. Wall coverings with the same color and pattern of those in the trailer were fixed in individual sham calf stalls for 6 h on the morning of transportation. Before transportation, calves were placed in a 3-compartment test apparatus with neutral walls and were able to move about freely for 15 min to habituate them to the test apparatus. Calves were CPA tested on d 2 after transportation. During the posttest, calves were placed in the test apparatus with 3 compartments including a neutral center pen (center), blue horizontal stripe compartment (side), and red vertical stripe compartment (side) for 30 min; calves were able to move throughout the apparatus freely. Time spent in each compartment was recorded using continuous observation and analyzed as a percentage of total time in the apparatus. Calves spent less time in the compartment associated with transportation compared with the compartment with no prior association (22% vs. 42% ± 3% of time in the transportation-association and no-association compartments, respectively); however, this behavior was not affected by transportation treatment. Results from this study suggest that calves may perceive transportation to be aversive regardless of duration but may also be attracted to exploring a novel stimulus.


Impact of sleep disorders in Japanese patients with functional dyspepsia (FD): nizatidine improves clinical symptoms, gastric emptying and sleep disorders in FD patients.
The association between functional dyspepsia (FD) and sleep disorders has yet to be studied in detail. The aim of this study is to evaluate the risk factors associated with sleep disorders and the clinical response to nizatidine therapy for sleep disorders in Rome III-based FD patients. We enrolled 94 FD patients and 52 healthy volunteers. We used Rome III criteria to evaluate upper abdominal symptoms, and the Self-Rating Questionnaire for Depression scores to determine depression status. Sleep disorder was evaluated using Pittsburgh Sleep Quality Index (PSQI) scores, and degree of anxiety by the State-Trait Anxiety Inventory. Gastric motility was evaluated. Thirty-four FD patients were treated with nizatidine (300 mg/day) or placebo for 4 weeks in a crossover trial. The primary end point of this study was to determine whether nizatidine could improve clinical symptoms and sleep disorders in FD patients. The global PSQI score for FD patients was significantly (P < 0.001) higher compared with healthy volunteers. There were significant correlations between global PSQI scores and total Gastrointestinal Symptom Rating Scale and Self-Rating Questionnaire for Depression scores (P < 0.001, P < 0.0001, respectively) in FD patients than in healthy volunteers. We found significant relationships between subjective sleep quality and both Tmax and T1/2 values in FD patients. Nizatidine significantly improved certain clinical symptoms, gastric emptying, and global PSQI score compared with placebo treatment. Sleep disorders in FD patients correlated significantly with both clinical symptoms of dyspepsia and depression compared with healthy volunteers. Nizatidine significantly improved gastroesophageal reflux symptoms, gastric emptying, and sleep disorders in FD patients.


Diacylglycerol kinase epsilon in bovine and rat photoreceptor cells. Light-dependent distribution in photoreceptor cells.
The present study shows the selective light-dependent distribution of 1,2-diacylglycerol kinase epsilon (DAGKɛ) in photoreceptor cells from bovine and albino rat retina. Immunofluorescence microscopy in isolated rod outer segments from bleached bovine retinas (BBROS) revealed a higher DAGKɛ signal than that found in rod outer segments from dark-adapted bovine retinas (BDROS). The light-dependent outer segment localization of DAGKɛ was also observed by immunohistochemistry in retinas from albino rats. DAGK activity, measured in terms of phosphatidic acid formation from a) [(3)H]DAG and ATP in the presence of EGTA and R59022, a type I DAGK inhibitor, or b) [γ-(32)P]ATP and 1-stearoyl, 2-arachidonoylglycerol (SAG), was found to be significantly higher in BBROS than in BDROS. Higher light-dependent DAGK activity (condition b) was also found when ROS were isolated from dark-adapted rat retinas exposed to light. Western blot analysis of isolated ROS proteins from bovine and rat retinas confirmed that illumination increases DAGKɛ content in the outer segments of these two species. Light-dependent DAGKɛ localization in the outer segment was not observed when U73122, a phospholipase C inhibitor, was present prior to the exposure of rat eyecups (in situ model) to light. Furthermore, no increased PA synthesis from [(3)H]DAG and ATP was observed in the presence of neomycin prior to the exposure of bovine eyecups to light. Interestingly, when BBROS were pre-phosphorylated with ATP in the presence of 1,2-dioctanoyl sn-glycerol (di-C8) or phorbol dibutyrate (PDBu) as PKC activation conditions, higher DAGK activity was observed than in dephosphorylated controls. Taken together, our findings suggest that the selective distribution of DAGKɛ in photoreceptor cells is a light-dependent mechanism that promotes increased SAG removal and synthesis of 1-stearoyl, 2-arachidonoyl phosphatidic acid in the sensorial portion of this cell, thus demonstrating a novel mechanism of light-regulated DAGK activity in the photoreceptors of two vertebrate species.


Natural purified porcine gastric inhibitory polypeptide (GIP) stimulates exocrine pancreas secretion due to contamination with a cholecystokinin-like substance.
The effects of purified natural gastric inhibitory polypeptide-enterogastrone III (GIP-EG III) and a fraction which is further purified by high pressure liquid chromatography (GIP-HPLC) were investigated on the endocrine and exocrine isolated perfused pancreas of rats. At the dose of 5 ng/ml used for both GIP preparations, only GIP-EG III significantly stimulated volume and amylase secretion of the exocrine pancreas. The response of insulin release to stimulation by GIP-EG III or GIP-HPLC was not significantly different. In the presence of cholecystokinin-octapeptide (CCK-8) at a concentration which gave half-maximal stimulation of amylase secretion, GIP-EG III almost doubled the response of the exocrine pancreas, whereas GIP-HPLC had no additional effect. CCK-8 alone significantly increased total insulin output under hyperglycemic conditions. We conclude that porcine GIP purified by gel chromatography contains a CCK-like substance which can be removed by further purification on high pressure liquid chromatography without affecting the insulinotropic activity. Some of the reported effects of GIP could be due to contamination.


Late presentation of intestinal malrotation: an argument for elective repair.
Midgut malrotation most commonly presents in young children. This diagnosis is not often entertained in the adolescent or adult with abdominal complaints. We reviewed our experience with this subset of malrotation patients. A retrospective review of medical records from adolescent or adult patients identified with a diagnosis of anomaly of intestinal fixation or malrotation, who were treated within our health system between 1993 and 2004. A total of 33 patients were diagnosed with malrotation and treated with Ladd's procedure. Acute abdominal pain was present in 50%, and chronic complaints were present in the other patients. Initial work-up included computed tomography (CT) scan (28%), upper gastrointestinal (UGI) study (38%), and plain films (47%) Postoperative complications occurred more frequently in patients that were operated on emergently (60%) than in those that underwent elective surgery (22%; p = 0.04). This large case series of intestinal malrotation in the nonpediatric age group suggests that Ladd's procedure can be performed very safely. Moreover, the results suggest that patients with known malrotation should have Ladd's procedure performed electively rather than urgently.


A novel tungsten diselenide nanoparticles for enhanced photocatalytic performance of Cr (VI) reduction and ciprofloxacin (CIP).
Nanoparticles (NPs) fabrication is a significant approach to enhance the visible light response of photocatalysts, to realize inexpensive and more harmful compound removal, at larger scale. The poor electrons and holes separation capability and low light activity of bulk materials can be notably enhanced through developing NPs. From photocatalytic investigation, better performance was received in the tungsten diselenide (WSe2) NPs than that in bare WSe2, exhibiting the action of restrained recombination of charge carriers in the NPs. The photocatalytic Cr(VI) reduction efficiency of WSe2 NPs is 2.7 folds greater than that by bare WSe2. On the other hand, the photocatalytic efficiency follows the order of nano WSe2-3 > nano WSe2-2 > nano WSe2-1 > bare WSe2, nano WSe2-3 is nearly 2.7 folds greater than that of bare WSe2. The results imply the fabrication of WSe2 NPs and it possesses improved visible light utilization. The proposed WSe2 NPs have merged with the three aspects of photocatalytic capability including the visible light activity, the valid separation of photo-response charge carriers and enough surface active sites owing to the nanoscale formed. This research endows conduct on the potential style of NPs for photo-response water environmental remediation.


A quantitative and qualitative method for direct 2-DE analysis of murine cartilage.
Direct 2-DE analysis of cartilage is difficult due to the high proteoglycan content. Proteoglycan removal before IEF may however cause the partial or total loss of specific proteins making this approach ineffective when quantitative data are required to investigate protein expression differences. Thus, we have developed a 2-DE method including passive rehydration loading that does not require sample pretreatment and allows direct protein expression studies in cartilage samples.


Vision-related quality of life in Japanese patients with wet age-related macular degeneration treated with intravitreal aflibercept in a real-world setting.
To evaluate vision-related quality of life (QoL) in wet age-related macular degeneration (wAMD) patients receiving intravitreal aflibercept (IVT-AFL). Prospective, observational Japanese postmarketing surveillance study. All decisions were made by the treating physician. QoL was assessed using the 25-item National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ-25) composite score administered at baseline, 6 months, and 12 months (primary assessment). Secondary assessments included NEI-VFQ-25 subscale scores, resource use, and best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution [logMAR]). In total, 576 patients (baseline), 555 patients (6 months), and 446 patients (12 months) were included. The mean (SD) number of IVT-AFL injections was 3.5 (1.2) at 6 months and 4.6 (2.2) at 12 months. The mean (SD) improvement from baseline in the NEI-VFQ-25 composite score was 3.1 (11.1) at 6 months and 2.7 (12.3) at 12 months (P < .0001). For the NEI-VFQ-25 subscale scores, the mean change was ≥ 4 (minimally important difference) for general vision, near vision, and mental health at 6 months, and for general vision and mental health at 12 months (all P < .0001). A significant improvement from baseline was found in mean BCVA (logMAR) at 6 months (-0.1) and 12 months (-0.1) (P < .0001). The mean change from baseline in the NEI-VFQ-25 scores was greatest in patients with improved BCVA (gain of ≤ -0.3 logMAR units or ≥ 15 letters) after treatment. IVT-AFL was associated with significant improvements in QoL and visual acuity in Japanese patients with wAMD in a real-world setting.


Dopaminergic neurons are preferentially responsive to advertisement calls and co-active with social behavior network nuclei in sneaker male midshipman fish.
Vocal species use acoustic signals to facilitate diverse behaviors such as mate attraction and territorial defense. However, little is known regarding the neural substrates that interpret such divergent conspecific signals. Using the plainfin midshipman fish model, we tested whether specific catecholaminergic (i.e., dopaminergic and noradrenergic) nuclei and nodes of the social behavior network (SBN) are differentially responsive following exposure to playbacks of divergent social signals in sneaker males. We chose sneaker (type II) males since they attempt to steal fertilizations from territorial type I males who use an advertisement call (hum) to attract females yet are also subjected to vocal agonistic behavior (grunts) by type I males. We demonstrate that induction of cFos (an immediate early gene product and proxy for neural activation) in two forebrain dopaminergic nuclei is greater in sneaker males exposed to hums but not grunts compared to ambient noise, suggesting hums preferentially activate these nuclei, further asserting dopamine as an important regulator of social-acoustic behaviors. Moreover, acoustic exposure to social signals with divergent salience engendered contrasting shifts in functional connectivity between dopaminergic nuclei and nodes of the SBN, supporting the idea that interactions between these two circuits may underlie adaptive decision-making related to intraspecific male competition.


Hodgkin Lymphoma-related Inflammatory Modification-displayed Castleman Disease-like Histological Features and Positron Emission Tomography/Computed Tomography Usefulness for the Differential Diagnosis: A Case Report.
Hodgkin lymphoma (HL) and idiopathic multicentric Castleman disease (iMCD) are markedly different conditions. However, in some cases, histological similarities caused by elevated cytokines, including IL-6, can lead to a misdiagnosis of HL as CL. We herein report a patient with HL who had been diagnosed with Castleman disease by an expert panel and for whom an additional biopsy was useful for determining the correct diagnosis. Furthermore, we analyzed the positron emission tomography/computed tomography findings at the diagnosis and found that the maximum standardized uptake value was useful for distinguishing HL from iMCD.


How Reliable Is Fluorescence-Guided Surgery in Low-Grade Gliomas? A Systematic Review Concerning Different Fluorophores.
Fluorescence-guided surgery has been increasingly used to support glioma surgery with the purpose of obtaining a maximal safe resection, in particular in high-grade gliomas, while its role is less definitely assessed in low-grade gliomas. A systematic review was conducted. 5-aminolevulinic acid, sodium fluorescein, indocyanine green and tozuleristide were taken into account. The main considered outcome was the fluorescence rate, defined as the number of patients in whom positive fluorescence was detected out of the total number of patients. Only low-grade gliomas were considered, and data were grouped according to single fluorophores. 16 papers about 5-aminolevulinic acid, 4 about sodium fluorescein, 2 about indocyanine green and 1 about tozuleristide were included in the systematic review. Regarding 5-aminolevulinic acid, a total of 467 low-grade glioma patients were included, and fluorescence positivity was detected in 34 out of 451 Grade II tumors (7.3%); while in Grade I tumors, fluorescence positivity was detected in 9 out of 16 cases. In 16 sodium fluorescein patients, seven positive fluorescent cases were detected. As far as indocyanine is concerned, two studies accounting for six patients (three positive) were included, while for tozuleristide, a single clinical trial with eight patients (two positive) was retrieved. The current evidence does not support the routine use of 5-aminolevulinic acid or sodium fluorescein with a standard operating microscope because of the low fluorescence rates. New molecules, including tozuleristide, and new techniques for fluorescence detection have shown promising results; however, their use still needs to be clinically validated on a large scale.


Selective 2'-benzoylation at the cis 2',3'-diols of protected ribonucleosides. New solid phase synthesis of RNA and DNA-RNA mixtures.
5'-0-(Dimethoxytrityl)-2'-0-(benzoyl or 3,4,5-trimethoxybenzoyl)-base protected ribonucleosides have been prepared by selective benzoylation of the 2'-hydroxyl group. The isomerization of the 2'-benzoates to the 3'-benzoates was studied. The protected ribonucleosides have been converted to either methylphosphochloridites or methylphosphoamidites and used to synthesize oligoribonucleotides on silica gel solid support. The synthetic RNA were deprotected and isolated using conditions that minimize internucleotide cleavage. The use of 2'-benzoates as protecting groups for ribonucleosides has made it possible to easily prepare and isolate mixtures of DNA and RNA.


The Aboriginal tea ceremony: its relevance to psychiatric practice.
To examine the elements of the Aboriginal tea ceremony and its relevance to psychiatric practice. Through the Aboriginal tea ceremony, the mental health professional is able to convey that care and concern balance experience and expertise. These underpinning principles have wide application.


Studies on photo-degradation of 2,4-dinitro toluene in aqueous phase.
The efficiency of different photo-degradation processes was evaluated for degrading 2,4-dinitro toluene (DNT) in aqueous phase. The rate and extent of DNT degradation and removal of total organic carbon (TOC) and total nitrogen (TN) contents were compared for direct photolytic and photo-oxidative reactions using various concentrations of H2O2 and Fenton's reagent with a 125 W medium pressure UV lamp. DNT was degraded rapidly under photo-oxidative conditions. Complete destruction was obtained using Fenton's reagent, wherein 100 ppm of DNT was degraded within 60 min of irradiation time. Removal of TOC and TN contents in the photo-Fenton system was 96% and 57%, respectively, after 2 h of UV irradiation. Degradation of DNT followed first order reaction kinetics. Photo-Fenton oxidation is found to be the most suitable technique to degrade DNT in aqueous phase.


Chrysin and chrysin-loaded nanocarriers induced immunogenic cell death on B16 melanoma cells.
Induction of immunogenic cell death (ICD) is a promising strategy for cancer immunotherapy. Chrysin, which has potential anticancer effects, faces limitations in clinical applications due to its poor water solubility. This study aimed to formulate chrysin with PEG-poly(α-benzylcarboxylate-ε-caprolactone) (PBCL) nanoparticles (NPs) and assess their anticancer and ICD-inducing potency in melanoma cells, comparing with free chrysin. The co-solvent evaporation method was employed to develop chrysin-loaded NPs. UV spectroscopy, dynamic light scattering, and the dialysis bag method were used to evaluate the encapsulation efficiency (EE), particle size, polydispersity index (PDI), and drug release profile, respectively. The anticancer effects of the drugs were assessed using the MTT and trypan blue exclusion assays. Flow cytometry was employed to evaluate apoptosis and calreticulin (CRT) expression. ELISA and western blotting were used to detect heat shock protein 90 (HSP90), Annexin A1, GRP78 (Glucose-related protein78), and activated protein kinase R-like endoplasmic reticulum kinase (p-PERK). Chrysin-loaded PEG-PBCL NPs (chrysin-PEG-PBCL) showed an EE of 97 ± 1%. Chrysin-PEG-PBCL was 38.18 ± 3.96 nm in size, with a PDI being 0.62 ± 0.23. Chrysin-PEG-PBCL showed an initial burst release, followed by sustained release over 24 h. Chrysin-PEG-PBCL exhibited a significantly stronger anticancer effect in B16 cells. Chrysin-PEG-PBCL was found to be more potent in inducing apoptosis. Both free chrysin and chrysin NPs induced ICD as indicated by an increase in the levels of ICD biomarkers. Interestingly, chrysin NPs were found to be more potent inducers of ICD than the free drug. These findings demonstrate that chrysin and chrysin-PEG-PBCL NPs can induce ICD in B16 cells. PEG-PBCL NPs significantly enhanced the potency of chrysin in inducing ICD compared to its free form.


Clopidogrel and the risk of osteoporotic fractures: a nationwide cohort study.
The P2Y(12) inhibitor clopidogrel inhibits platelet aggregation and is used in the treatment and prevention of coronary artery disease. It is widely used and, in combination with acetylsalicylic acid, is the standard of care for acute coronary syndrome and percutaneous coronary intervention. The mode of action of clopidogrel involves pathways that are important to the metabolic activity in bone cells, although to our knowledge whether P2Y(12) receptors are involved in the regulation of bone metabolism has not yet been investigated. Therefore, the objective of the present study was to investigate the association between clopidogrel use and risk of fractures. We investigated the association between clopidogrel use and fracture incidence in a nationwide cohort study within the Danish population of approximately 5.3 million individuals. All patients who were prescribed clopidogrel during the years 1996-2008 were included in the study (n = 77 503), and three nonusers were randomly selected, matched for age and gender (n = 232 510), for each clopidogrel-treated subject. Treatment with clopidogrel was associated with both increased overall fracture risk and increased risk of osteoporotic fractures, especially in subjects with a treatment duration of more than 1 year. However, individuals with low exposure to clopidogrel (<0.01 defined daily dose) had a lower risk of fracture than never users. Use of the P2Y(12) inhibitor clopidogrel is associated with risk of fractures. There seems to be a biphasic relation so that lower doses are associated with decreased fracture risk, whereas higher doses (recommended dose range) are associated with increased risk. More studies are warranted to determine the potential in vivo effect of platelet aggregation inhibitors on bone metabolism.


Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance.
Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side population that is characteristically enriched in normal and cancer stem cells. Numerous tumors depend on unregulated EGFR signaling, thus inhibition of this receptor by small molecular weight inhibitors such as gefitinib, and the novel second generation agents vandetanib, pelitinib and neratinib, is a promising therapeutic option. In the present study, we provide detailed biochemical characterization regarding the interaction of these EGFR inhibitors with ABCG2. We show that ABCG2 confers resistance to gefitinib and pelitinib, whereas the intracellular action of vandetanib and neratinib is unaltered by the presence of the transporter. At higher concentrations, however, all these EGFR inhibitors inhibit ABCG2 function, thereby promoting accumulation of ABCG2 substrate drugs. We also report enhanced expression of ABCG2 in gefitinib-resistant non-small cell lung cancer cells, suggesting potential clinical relevance of ABCG2 in acquired drug resistance. Since ABCG2 has important impact on both the pharmacological properties and anti-cancer efficiencies of drugs, our results regarding the novel EGFR inhibitors should provide useful information about their therapeutic applicability against ABCG2-expressing cancer cells depending on EGFR signaling. In addition, the finding that these EGFR inhibitors efficiently block ABCG2 function may help to design novel drug-combination therapeutic strategies.


Relative risk of cervical cancer in indigenous women in Australia, Canada, New Zealand, and the United States: a systematic review and meta-analysis.
We performed a systematic review and meta-analysis of cervical cancer risk in indigenous women in Australia, Canada, New Zealand, and the United States, in order to identify whether risks of cervical dysplasia, cervical cancer, and cervical cancer-related mortality are higher in indigenous relative to non-indigenous populations. We identified 35 studies published in 1969-2008. In our findings, indigenous populations did not have an elevated risk of cervical dysplasia or carcinoma in situ relative to non-indigenous populations, but had elevated risks of invasive cervical cancer (pooled RR=1.72) and cervical cancer-related mortality (pooled RR=3.45). There was a log-linear relationship between relative risk and disease stage. In conclusion, the indigenous women have a markedly higher risk of cervical cancer morbidity and mortality than non-indigenous women, but no increased risk of early-stage disease, suggesting that structural, social, or individual barriers to screening, rather than baseline risk factors, are influencing poor health outcomes.


Treatment Strategies of Improving Quality of Care in Patients With Heart Failure.
Heart failure (HF) is a global health problem closely related to morbidity and mortality. As the burden of HF increases, it is necessary to manage and treat this condition well. However, there are differences between real-world practice and guidelines for the optimal treatment for HF. Patient-related, healthcare provider-related, and health system-related factors contribute to poor adherence to optimal care. This review article aims to examine HF treatment patterns and treatment adherence in real-world practice, identify clinical gaps to suggest ways to improve the quality of care for HF and clinical outcomes for patients with HF. Although it is important to optimize treatment based on evidence-based guidelines to the greatest extent, it is known that there is still poor treatment adherence, and many patients do not receive guideline-directed medical therapy, especially at the early stages. To improve medication adherence, qualitative evaluation through performance measurement, as well as education of patients, caregivers and medical staff through a multidisciplinary approach are important.


Synthesis and evaluation of novel fluorinated hematoporphyrin ether derivatives for photodynamic therapy.
A photosensitizer with high phototoxicity, suitable amphipathy and low dark toxicity could play a pivotal role in photodynamic therapy (PDT). In this study, a facile and versatile approach was adopted to synthesize a series of novel fluorinated hematoporphyrin ether derivatives (I1-I5 and II1-II4), and the photodynamic activities of these compounds were studied. Compared to hematoporphyrin monomethyl ether (HMME), all PSs showed preferable photodynamic activity against A549 lung tumor cells. The longest visible absorption wavelength of these compounds was approximately 622 nm. Among them, II3 revealed the highest singlet oxygen yield (0.0957 min-1), the strongest phototoxicity (IC50 = 1.24 μM), the lowest dark toxicity in vitro, and exhibited excellent anti-tumor effects in vivo. So compound II3 could act as new drug candidate for photodynamic therapy.


Childhood memory and self-description in young Chinese adults: the impact of growing up an only child.
This study examined the relationship between self-description and childhood memory in 255 Chinese young adults. Ninety-nine participants were from only child families and 156 had siblings. All participants completed two questionnaires: a version of the Twenty Statements Test of Kuhn and McPartland (Kuhn, M.H., McPartland, T.S., 1954. An empirical investigation of self-attitudes. American Sociological Review 19, 68-76) eliciting self-descriptions, and an instrument asking for earliest and other childhood memories. Based on theories positing a relationship between autobiography and the organization of the self, we predicted differences on both measures between only- and sibling-child participants. Findings indicated that compared with sibling children, only children had more private and fewer collective self-descriptions, earlier first memories, more specific and more self-focused memories. In addition, autobiographical measures were influenced by cohort, gender, preschool attendance, and urban/rural family effects. Findings are discussed in terms of literature on autobiography, the self and childhood in China.


(Dis)concordance of comorbidity data and cancer status across administrative datasets, medical charts, and self-reports.
Benchmarking outcomes across settings commonly requires risk-adjustment for co-morbidities that must be derived from extant sources that were designed for other purposes. A question arises as to the extent to which differing available sources for health data will be concordant when inferring the type and severity of co-morbidities, how close are these to the "truth". We studied the level of concordance for same-patient comorbidity data extracted from administrative data (coded from International Classification of Diseases, Australian modification,10th edition [ICD-10 AM]), from the medical chart audit, and data self-reported by men with prostate cancer who had undergone a radical prostatectomy. We included six hospitals (5 public and 1 private) contributing to the Prostate Cancer Outcomes Registry-Victoria (PCOR-Vic) in the study. Eligible patients from the PCOR-Vic underwent a radical prostatectomy between January 2017 and April 2018.Health Information Manager's in each hospital, provided each patient's associated administrative ICD-10 AM comorbidity codes. Medical charts were reviewed to extract comorbidity data. The self-reported comorbidity questionnaire (SCQ) was distributed through PCOR-Vic to eligible men. The percentage agreement between the administrative data, medical charts and self-reports ranged from 92 to 99% in the 122 patients from the 217 eligible participants who responded to the questionnaire. The presence of comorbidities showed a poor level of agreement between data sources. Relying on a single data source to generate comorbidity indices for risk-modelling purposes may fail to capture the reality of a patient's disease profile. There does not appear to be a 'gold-standard' data source for the collection of data on comorbidities.


Modifications of anticipatory postural adjustments in a rock climbing task: the effect of supporting wall inclination.
The aim of this study was to analyse the influence of initial postural constraint on the realisation of a leg release in a rock climbing task. Two conditions were tested: a vertical posture and an overhanging posture. The overhanging posture was characterised by a large sustentation base, which enhanced the mechanical possibilities of the system. Subjects had to release their right foot in both postural conditions. In the vertical posture, movement's effectuation was associated with anticipatory postural adjustments (APAs). In the overhanging posture, the movement was performed without APAs. The results indicated that APAs were modulated according to the possibilities of force creation of the system. Hence, the disappearance of APAs in the overhanging posture was explained by the efficiency of the system to create the impulse necessary to perform the task.


Lysine demethylase KDM3A regulates breast cancer cell invasion and apoptosis by targeting histone and the non-histone protein p53.
Invasive growth and apoptosis resistance of breast cancer cells are associated with metastasis and disease relapse. Here we identified that the lysine-specific demethylase KDM3A played a dual role in breast cancer cell invasion and apoptosis by demethylating histone and the non-histone protein p53, respectively. While inducing pro-invasive genes by erasing repressive histone H3 lysine 9 methylation, KDM3A promotes chemoresistance by demethylating p53. KDM3A suppressed pro-apoptotic functions of p53 by erasing p53-K372me1, as this methylation is crucial for the stability of chromatin-bound p53. Unexpectedly, depletion of KDM3A was capable of reactivating mutated p53 to induce the expression of pro-apoptotic genes in breast cancer with mutant p53. Moreover, KDM3A knockdown also potently inhibited tumorigenic potentials of breast cancer stem-like cells and rendered them sensitive to apoptosis induced by chemotherapeutic drugs. Taken together, our results suggest that KDM3A might be a potential therapeutic target for human breast cancer treatment and prevention.


Genetic variations using whole-exome sequencing might predict response for neoadjuvant chemoradiotherapy in locally advanced rectal cancer.
A good pathologic response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is associated with a better prognosis. However, there is no effective method to predict CRT response in LARC patients. Therefore, this study used whole-exome sequencing (WES) to identify novel biomarker predicting CRT benefit in LARC. Two independent tumor tissue sets were used to evaluate the genetic differences between the good CRT response group (15 patients achieved a pathologic complete response (pCR)) and the poor CRT response group (15 patients with pathologic stage III). After applying WES to the discovery set of 30 patients, additional samples (n = 67) were genotyped for candidate variants using TaqMan or Sanger sequencing for validation. Overall, this study included a total of 97 LARC patients. In the discovery and validation set, there was no known genetic mutation to predict response between two groups, while five candidate variants (BCL2L10 rs2231292, DLC1 rs3816748, DNAH14 rs3105571, ITIH5 rs3824658, and RAET1L rs912565) were found to be significantly associated with pCR. In the dominant model, the GC/CC genotype of DLC1 rs3816748 (p = 0.032), AC/CC genotype of DNAH14 rs3105571 (p = 0.009), and TT genotype of RAET1 rs912565 (p < 0.0001) were associated with a higher pCR rate. In the recessive model, BCL2L10 rs2231292 (p = 0.036) and ITIH5 rs3824658 (p = 0.003) were significantly associated with pCR. In the co-dominant model, 4 candidate variants (DLC1 rs3816748, DNAH14 rs3105571, ITIH5 rs3824658, and RAET1L rs912565) were significantly correlated with pCR. However, none of the candidate variants was associated with relapse-free or overall survival. The present results suggest that genetic variations of the BCL2L10 rs2231292, DLC1 rs3816748, DNAH14 rs3105571, ITIH5 rs3824658, and RAET1L rs912565 genes can be used as biomarkers predicting the CRT response for patients with LARC.


[Relationship between the polymorphism of growth hormone receptor Ex3 and the efficacy of rhGH treatment in children with idiopathic short stature].
To assess the influence of growth hormone receptor (GHR) Ex3 genotype on the short-term response to recombinant human growth hormone (rhGH) therapy in children with idiopathic short stature (ISS). Thirty prepubertal children with ISS receiving rhGH treatment [0.116±0.02 IU/(kg/d)] were randomly recruited. The GHR Ex3 locus was genotyped using a PCR multiplex assay. The growth data including growth velocity, height SDS for chronological age (HtSDSCA), height SDS for bone age (HtSDSBA) and predict final height were compared in children with different GHR genotypes 6 months after rhGH treatment. After 6 months of rhGH treatment, the children with ISS carrying d3/d3 alleles showed a significantly higher increment in growth velocity than those carrying fl/fl alleles (6.3±1.6 cm/year vs 3.4±0.5 cm/year; P<0.05). The polymorphism in GHR Ex3 is associated with the responsiveness to rhGH treatment, showing that the growth velocity in ISS children with d3/d3 genotype is significantly higher than those with fl/fl genotype.


Clinical complexity and diabetes: a multidimensional approach for the management of cardiorenal metabolic syndrome.
Diabetes mellitus (DM) is one of the fastest-growing health emergencies of the 21st century, and one of the chronic diseases with the highest socio-economic impact on health care systems. DM is the main cause of chronic kidney disease, and is associated with a significant increase in cardiovascular risk and clinical and care complexity. The presence of a constellation of cardiac, metabolic, and renal diseases, in a complex patient with DM, constitutes the CardioRenal Metabolic Syndrome (CRMS). The management of these patients should include a paradigm shift from a reactive strategy to a proactive approach, and the integration of territorial, hospital and social assistance services according to the Chronic Care Model (CCM). Complexity science suggests an alternative model in which disease and health arise from complex, dynamic, and unique interactions among the different components of the overall system. The hospital should be viewed as a highly specialized hub of the chronic care system, which interacts with the outpatient specialist and primary care. In order to create effective communication among territorial care units and highly specialized hospitals, levels of clinical complexity are here proposed and included in a multidimensional management model for the complex patient with diabetes and cardiorenal comorbidity.


[Stewart-Treves syndrome: hemangiosarcoma in chronic lymphedema. Ultrastructural analysis of various clinical developmental stages].
Ultrastructural studies of angiosarcoma in chronic lymphedema (Stewart-Treves syndrome) at various stages of development show that endothelial cell proliferation originates not in the lymphatic but in the blood capillary vessels. The results indicate that the term "lymphangiosarcoma" is no longer suitable to describe the histopathologic characteristics of Stewart-Treves syndrome.


ATP Impedes the Inhibitory Effect of Hsp90 on Aβ40 Fibrillation.
Heat shock protein 90 (Hsp90) is a molecular chaperone that assists protein folding in an Adenosine triphosphate (ATP)-dependent way. Hsp90 has been reported to interact with Alzheimeŕs disease associated amyloid-β (Aβ) peptides and to suppress toxic oligomer- and fibril formation. However, the mechanism remains largely unclear. Here we use a combination of atomic force microscopy (AFM) imaging, circular dichroism (CD) spectroscopy and biochemical analysis to quantify this interaction and put forward a microscopic picture including rate constants for the different transitions towards fibrillation. We show that Hsp90 binds to Aβ40 monomers weakly but inhibits Aβ40 from growing into fibrils at substoichiometric concentrations. ATP impedes this interaction, presumably by modulating Hsp90's conformational dynamics and reducing its hydrophobic surface. Altogether, these results might indicate alternative ways to prevent Aβ40 fibrillation by manipulating chaperones that are already abundant in the brain.


The precision of velocity discrimination across spatial frequency.
The precision of velocity coding for moving stimuli of different spatial frequencies was assessed by measuring velocity discrimination thresholds for a 1-c/deg grating paired with a grating whose spatial frequency ranged from 0.25 to 4 c/deg and for grating pairs of the same spatial frequency (0.25, 1, and 4 c/deg). The gratings always moved upward, with velocities ranging from 0.5 to 16 deg/sec. Velocity discrimination was as precise for stimuli that varied in spatial frequency by +/- 2 octaves (0.25 vs. 1 c/deg and 4 vs. 1 c/deg) as for stimuli of the same spatial frequency, for specific ranges of velocity that depended on the spatial and, therefore, the temporal frequencies of the stimuli. Compared with a 1-c/deg grating, the perceived velocity of 4-c/deg gratings was about 1.3 times faster and that of 0.25-c/deg gratings was about 1.3 times slower. Although these perceived velocity biases imply variation of velocity-signal processing among spatial frequency channels, the discrimination results indicate that the motion-sensing system can compare signals across different spatial frequency channels to make fine velocity discrimination within appropriate temporal frequency limits.


Pericarditis associated with nickel hypersensitivity to the Amplatzer occluder device: a case report.
A 38-year-old man with a history of migraine headaches with aura and one episode of ischemic stroke was found to have a patent foramen ovale (PFO). After percutaneous closure with the nickel-containing Amplatzer PFO occluder, the patient developed pericarditis, atrial fibrillation, and increased migraine headaches with aura that abated with oral prednisone. He tested positive for nickel hypersensitivity, which we conclude is the likely etiology of his pericarditis.


Methyl-terminated graphite carbon nitride with regulatable local charge redistribution for ultra-high photocatalytic hydrogen production and antibiotic degradation.
Intramolecular-tailored graphite carbon nitride (g-C3N4) has great potential to greatly optimize the photo-response performance and carrier separation ability, but exquisite molecular structure engineering is still challenging. Firstly, a series of oxygen and terminal methyl moiety co-modified g-C3N4 (CNNx) has been systematically prepared by using N-Hydroxysuccinimide (HOSu) as a novel copolymerized precursor and urea. The density functional theory (DFT) calculations demonstrated that the presence of oxygen can lower the binding energy for the C-C bond to make the terminal modification easier. The terminal methyl and Oxygen not only caused abundant alveolar defects to break the periodic symmetry but also acted as an electron-accepting platform to tune the local charge redistribution within g-C3N4 molecular. The synthesized CNNx (CNN25) achieved ultra-high photocatalytic activity and chemical stability under visible light toward antibiotic degradation (99% tetracycline, 92% doxycycline, 65% ofloxacin and 74% sulfathiazole degradation within 30 min) and hydrogen production (an apparent quantum efficiency of 2.10% at 400 nm). CNN25 also maintains good efficiency in surface water and groundwater. Moreover, the TC solution treated with CNN25 had hardly any harm to the growth of E. coli. We believe our findings will provide a facile and green strategy for the preparation of non-metallic modified g-C3N4.


Advocating for evidence in birth: Proving cause, effecting outcomes, and making the case for 'curers'.
The notion of 'evidence' circulates in two realms of current maternity care: biomedical 'evidence-based' obstetrics and efforts to reform conventional obstetric practices. I observed that in California's childbearing culture, 'evidence' is a boundary object that allows diverse actors to engage in related conversations despite fundamentally different assumptions about what evidence is or does. Sometimes these actors form productive hybrids and other times they talk past one another. This article uses recent work from the history and philosophy of science to distinguish the biomedical use of evidence, which is based on controlled experiments to prove cause and effect, from reformists' use of evidence, which foregrounds patient outcomes. Using Stengers's classification of doctors, charlatans, and curers, I discuss the role of rationality and experience in producing authoritative knowledge. Reformists' use of evidence, in effect, challenges medical power dynamics on what they perceive to be the terms of medical authority itself; in doing so, it has the potential to fundamentally alter who is the primary beneficiary of medical protocols. The challenge is continuing to use evidence in a way that doesn't simply ossify a new set of norms, but becomes increasingly capacious, flexible, specific, and patient centered.


Thermo- and pH-sensitive glycosaminoglycans derivatives obtained by controlled grafting of poly(N-isopropylacrylamide).
Poly(N-isopropyl acrylamide) grafted heparin and chondroitin sulfate were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The copolymers were characterized by NMR, IR, SEC, DLS, SLS and NTA methods. High grafting densities were reached for both glycosaminoglycans. The temperature, pH and polymer concentration affected the low critical solution temperatures values. The increased pNIPAAm chain length, grafting density and concentration led to the sharp phase transition at 35 °C. Spherical nanogels were formed around this temperature. Terminal dodecyl trithiocarbonate groups of the copolymers were reduced to thiols that allowed formation of sensitive nanogels with sharp phase transitions induced by pNIPAAm chains. The copolymers showed no toxicity to the ocular cells and they provided the prolonged release of dexamethasone phosphate at 37 °C. These copolymers are interesting alternatives for ocular drug delivery.


Peak pressure curve: an effective parameter for early detection of foot functional impairments in diabetic patients.
A clinical investigation was conducted on 61 diabetic patients and 22 healthy volunteers. Joint mobility, muscular function of the foot-ankle complex and plantar pressure measurements were characterised. A clustering algorithm was applied to obtain patient classification based on the shape and amplitude of the time curve of the instantaneous maximum pressure the foot experienced during gait. Results indicate that a screening test based on the peak pressure curve might be an effective way to detect diabetic patients at risk of foot ulceration.


Weak impact of fine-scale landscape heterogeneity on evolutionary potential in Arabidopsis lyrata.
Microhabitat heterogeneity can lead to fine-scale local adaptation when gene flow is restricted, which may be important for the maintenance of genetic variation within populations. This study tested whether microhabitat heterogeneity was associated with trait differences in a population of Arabidopsis lyrata and studied its impact on the genetic variance-covariance (G) matrix. Maternal seed families were collected from dune tops and bottoms, two microhabitats known to vary significantly in water availability. In a common garden experiment, replicate individuals per family were raised under wet and dry conditions, and physiological, morphological and life-history traits were assessed. Plants from the two microenvironments differed in their response to treatment in two performance components, in stomata density and most strongly in flowering time. Under wet conditions, plants originating from dune bottoms flowered 4 weeks earlier than those from dune tops. Only one of three G-matrix comparisons revealed that habitat heterogeneity and evolutionary potential were positively linked. The number of independent trait dimensions was larger in the entire population than within subpopulations separated by microhabitat under wet conditions. However, the size of the G-matrix was no larger in the entire population than within subpopulations separated by microhabitat, and trait correlation structure between microhabitats and treatments was not significantly different. These results indicate that fine-scale habitat heterogeneity likely led to local adaptation, which weakly affected levels of across-trait genetic variation.


Electromechanical response times in the knee muscles in young and old women.
The aim of the study was to compare electromechanical response times [total reaction time (TRT), pre-motor time (PMT), and electromechanical delay] in the knee muscles in groups of young and older women during release of peak torque (PT). Fifty women (1 group approximately 20 years of age and the other approximately 60 years of age) participated in the study. PT and electromyographic activity were measured for flexors and extensors of the right and left knee in static conditions in response to a visual stimulus. Significantly longer TRTs (P = 0.05) and PMTs (P = 0.05) were found in the group of older women compared with the younger participants. Asymmetry was found between the older and the younger group of women in PT of knee flexors. Significantly longer TRT and PMT phases in the group of older women suggests a longer time for information processing in the central nervous system in older people. Muscle Nerve 56: E147-E153, 2017.


Koch is dead.
Although the foundation of Koch's postulates, that "if an agent is the cause of disease in one individual it should be capable of causing disease in a second individual," is basically sound, the ritual that has evolved into present day experimental studies has obscured almost completely what occurs in natural processes outside the laboratory. Through a series of examples, it is emphasized that just bringing the host and the parasite together is not enough, but that the circumstances under which this is done is equally important. These circumstances include: the prior history of the host; the host's behavioral patterns, environmental conditioning, and disease history; the circumstances of exposure; and the environmental factors related to the host and the parasite. Of equal importance is the individual variation (genetic, physiologic, immunologic, etc.) of the host and the individual variation (strains, immunogenicity, pathogenicity, virulence, etc.) of the parasite. Because the rigor of the present day "scientific method" demands clearcut and reproducible results and investigations require predictable performance of the parasite in an evenly maintained host that is in a highly constrained environment, we should not wonder why we cannot produce the events of nature. If we are going to understand diseases of wildlife, we must consider the genetic heterogenicity of the host and parasite population, and recognize the complexity of the environment in which both exist. Koch's postulates, in the narrow sense, will help us to identify parasitisms but will not provide us with an understanding of information about diseases in wildlife; the real significance of these parasitisms to the health of the individual and to the size of the population.(ABSTRACT TRUNCATED AT 250 WORDS)


Endovascular Perforation Murine Model of Subarachnoid Hemorrhage.
Subarachnoid hemorrhage (SAH) is a subtype of stroke with disastrous outcomes of high disability and mortality. A variety of endeavors have been developed to explore a SAH animal model for investigation of the disease. Among these models, the endovascular perforation SAH model was considered to be the most simulative to the clinical human SAH because it reproduces several pathophysiology procedures and presents some of the most important post-hemorrhage features. An applicable SAH animal model should have the characteristics of low mortality rate, limited surgical manipulation, and adaptation to many species, which permits reproducibility and standardization. An intensive discussion of how to improve the techniques and refine the procedure has taken place in the last decade. This report describes our experiences with a murine model of SAH. We aim to standardize and optimize the procedures to establish a relatively stable animal model for SAH research.