Sustainability of a Compartmentalized Host-Parasite Replicator System under Periodic Washout-Mixing Cycles.
The emergence and dominance of parasitic replicators are among the major hurdles for the proliferation of primitive replicators. Compartmentalization of replicators is proposed to relieve the parasite dominance; however, it remains unclear under what conditions simple compartmentalization uncoupled with internal reaction secures the long-term survival of a population of primitive replicators against incessant parasite emergence. Here, we investigate the sustainability of a compartmentalized host-parasite replicator (CHPR) system undergoing periodic washout-mixing cycles, by constructing a mathematical model and performing extensive simulations. We describe sustainable landscapes of the CHPR system in the parameter space and elucidate the mechanism of phase transitions between sustainable and extinct regions. Our findings revealed that a large population size of compartments, a high mixing intensity, and a modest amount of nutrients are important factors for the robust survival of replicators. We also found two distinctive sustainable phases with different mixing intensities. These results suggest that a population of simple host-parasite replicators assumed before the origin of life can be sustained by a simple compartmentalization with periodic washout-mixing processes.


Significance of 195 bp-enhancer of PdCYP51B in the acquisition of Penicillium digitatum DMI resistance and increase of fungal virulence.
Two sterol 14α-demethylase genes from Penicillium digitatum, PdCYP51A and PdCYP51B, were evaluated and revealed that 95% of Imazalil (IMZ)-resistant isolates carried a 195-bp insertion in the PdCYP51B promoter. We functionally characterized both sterol 14α-demethylases by overexpression. Molecular analysis of overexpression mutants showed that the introduction of PdCYP51B insertion is more stable than the five-tandem repeat PdCYP51A sequence previously described that confers DMI fungicide resistance. The both enhancers can coexist in P. digitatum isolates that initially contained the 195-bp PdCYP51B insertion but the introduction of 195-bp PdCYP51B enhancer promoted the loss of the five-tandem repeat of PdCYP51A. The incorporation of 195-bp PdCYP51B resulted in an increase of DMI fungicide resistance in mutants from already resistant isolates and confers resistance to DMIs in mutants from sensitive isolates. Transcription evaluation of the both genes showed noticeable induction in all overexpression mutants, except for those coming from the five-tandem repeat PdCYP51A sequence, whereas PdCYP51A expression dropped dramatically. Only PdCYP51B exhibited up-regulation during citrus infection compared to axenic growth, and the role of PdCYP51B in fungal virulence was further reinforced since strains with low virulence showed increased infectivity in overexpression mutants. This study suggested the predominant role of the PdCYP51B enhancer in the acquisition of DMI resistance and fungal virulence, by replacing homologues genes with same putative function.


Longitudinal study of clinical, neurophysiological and immunological parameters in multiple sclerosis. Preliminary investigation.
Thirty subjects affected with multiple sclerosis, of which 22 were female and eight male, with an average of 30 +/- 7, years were studied, for a period of 10-15 months,. clinically using Kurtzkes' report form, neurophysiologically (responses tested: VEP, BAEP, SEP, ESG) and immunologically (Rosette Et, Ea, EAC). Of the 30 cases, 19 showed poussées in the last three years and 11 were in the stabilization phase. The Kurtzke reports and the neurophysiological tests permitted an accurate assessment of lesion levels and their rate of evolution. The immunological tests showed a notable ability to differentiate between subjects with recent poussées and those in the stabilization phase presenting overall values significantly below the norm. In the follow-up, after treatments with methisoprinol, the immunological tests also revealed modifications of notable interest.


Multi-detector row CT versus coronary angiography: preoperative evaluation before totally endoscopic coronary artery bypass grafting.
To assess multi-detector row spiral computed tomography (CT) for preoperative evaluation of patients undergoing totally endoscopic coronary artery bypass grafting and to correlate the data with coronary angiographic and intraoperative findings. Thirty-six patients preoperatively underwent multi-detector row CT (4 x 1-mm collimation, pitch of 1.5, 500-msec rotation time, retrospective electrocardiographic gating, 1.25-mm effective section thickness) and coronary angiography. Assessment criteria for both techniques were visibility and cardiac course of coronary arteries, localization and degree of stenoses, composition of atherosclerotic plaques, and vascular diameter at anastomosis site. Site for distal bypass anastomosis was recommended. Results at multi-detector row CT were calculated relative to results at coronary angiography and surgery. Multi-detector row CT properly displayed 79.4% (154 of 194) of all surgical relevant coronary segments and 80.4% (434 of 540) of all coronary segments. For coronary angiography, ratios of 88.7% (172 of 194) and 94.6% (511 of 540), respectively, were observed. For detection of calcified plaques, multi-detector row CT results exceeded those at coronary angiography by a difference of 17% (18 of 18 [100%] compared with 15 of 18 [83%]). Hemodynamically relevant stenoses were identified with multi-detector row CT in 76% (42 of 55) of cases. Bridging of coronary segments through either myocardium (four of five) or epicardial fat (two of three) was better identified at multi-detector row CT than it was at coronary angiography (one of five compared with zero of three, respectively). At multi-detector row CT, 76% (28 of 37) of all distal bypass touchdown segments were identified, but at coronary angiography, only 70% (26 of 37) were identified. Multi-detector row CT provides extended information about coronary target site and therefore should be regarded as an ideal additive planning tool for complex minimally invasive procedures such as totally endoscopic coronary artery bypass grafting or minimally invasive direct coronary artery bypass grafting.


Pellet formulations of sex pheromone components for mating disruption of oriental beetle (Coleoptera: Scarabaeidae) in turfgrass.
Wax-based pelleted sex pheromone formulations were tested for efficacy in managing oriental beetle, Anomala orientalis Waterhouse, in turfgrass. Four pellet formulations were field tested at 25 g pheromone/ha during 2006 and 2007. Application patterns included pellets specifically placed in a uniform grid pattern and pellets scattered by a broadcast spreader. Treatment efficacy was measured by monitoring male A. orientalis captures in pheromone-baited traps, determining mating success of confined virgin females, and estimating subsequent densities of A. orientalis larvae in soil/sod samples. All formulation and application pattern combinations effectively suppressed mating for 2 wk after application as measured by reduction in male trap captures and mating success of confined virgins. Two formulations gradually lost efficacy beginning 2 wk after application and the two others after 3-4 wk. Application pattern had no effect on trap captures. The most effective formulation reduced trap captures by >/=90% for 36 d, reduced mating success of confined females by 86-100% until 24 d after treatment, and reduced A. orientalis larval populations by 69%. In a previous study, sprayable formulations resulted in nuisance contamination of shoes that attracted male beetles outside of pheromone-treated areas. In contrast, shoes walked through pellet-treated areas did not attract male beetles. Pellet formulations have great potential for A. orientalis mating disruption, but more research is needed to optimize performance.


Research considerations in the evaluation of minimally invasive pancreatic resection (MIPR).
The IHPBA/AHPBA-sponsored 2016 minimally invasive pancreatic resection (MIPR) conference held on April 20th, 2016 included a session designed to evaluate what would be the most appropriate scientific contribution to help define the increasing role of MIPR internationally. Participants in the conference reviewed the assessment of numerous pertinent scientific designs including randomized controlled trial (RCT), pragmatic international RCT, registry-RCT, non-RCT with propensity matching, and various types of clinical registries including those aiming to create a quality improvement data system or a learning health care system. The strengths and weaknesses of each of these designs, the status of trials which are currently recruiting patients, and pragmatic considerations were evaluated. A recommendation was made to establish a clinical registry to collect data prospectively from around the world to assess current practices and provide a framework for future studies in MIPR.


The aging male population and medical care for benign prostatic hyperplasia in Canada.
The male Canadian population is aging and more men will be seeking medical care for benign prostatic hyperplasia (BPH). We examined the projected increase in older Canadian males between 2005 and 2018 to evaluate urologic health-care needs. We used Statistics Canada population projections to derive predictions of the male population aged 50 or more from 2005 to 2018 and results from the Olmsted County Study of Urinary Symptoms to estimate numbers of males aged >/=50 with moderate to severe lower urinary tract symptoms (msLUTS) in the same period. Data from the Canadian Institute for Health Information were used to estimate the number of urologists in 2018. The number of Canadian men aged >/=50 is projected to rise between 2005 and 2018 by 39.5% and the number with msLUTS by 41.3%. However, the number of practicing urologists in Canada in 2018 is likely to be similar to the 584 practicing in 2007. An increase in the number of urologists proportional to the increase in men aged >/=50 with msLUTS would require 799 urologists in 2018. Little opportunity exists to expand the number of trainees in urology. Other alternatives must be sought to deal with increased numbers of older men with msLUTS. Initial management of BPH has moved towards being a responsibility of primary care physicians, but they appear to view BPH as a quality-of-life issue. It is crucial that urologists work closely with primary care physicians to ensure that the management of LUTS progression is optimized.


The results of angiographic studies of abdominal masses.
This study reveals the continuing great viability of angiography in the investigation of abdominal masses. It is a fundamentally important procedure within the context of presurgical evaluation. Certain points should be underlined. - The radiological definition of the histological nature of an abdominal mass during angiography remains difficult, practically impossible in certain regions. - Borrowed vascularizations still pose complex diagnostic problems at different levels. - The benefit of angiography should be compared with other modern radiodiagnostic methods, especially the less aggressive ones. - The importance of each of these points has led us to develop them separately: - The diagnostic reliability of angiography in abdominal masses (from anatomico-radiological correlations). To be published - The borrowed vascularisation of abdominal masses. To be published - The tomodensitometry of abdominal masses. To be published - Diagnostic strategy in case of an abdominal mass. To be published.


An empirical analysis of eating disorder, not otherwise specified: preliminary support for a distinct subgroup.
In recent years, there has been debate concerning whether distinct subgroups exist within the eating disorder, not otherwise specified (EDNOS) diagnostic category. One subgroup that has been suggested is binge-eating disorder (BED). While BED has received some research attention, relatively little is known about other possible subgroups within the EDNOS category. The purpose of the present study is to empirically investigate whether distinct subgroups exist within the diagnostic category of EDNOS. Participants were 53 EDNOS patients who presented to psychotherapy clinics for treatment of an eating disorder. Information gathered from a clinical assessment, which included a clinical interview and self-report questionnaires, was used in the analyses of the study. Using cluster analytic procedures, two subgroups of patients diagnosed with EDNOS were identified. The two subgroups differed from each other in terms of weight, binging, and body image variables. Specifically, the second subgroup (of 11 patients) appeared to be a distinct subgroup of overweight binge-eating patients, while the first subgroup appeared to be a heterogenous group of EDNOS patients. The overweight binge-eating subgroup was significantly higher in current weight, in reported highest adult weight, in reported higher lowest adult weight, and had more binges per week than the heterogenous EDNOS subgroup. Interestingly, the two subgroups did not differ in terms of self-reported purging and/or compensatory behaviors (e.g., vomiting and laxative use). The results of the present study provide preliminary support for a distinct subgroup within the EDNOS diagnostic category. This subgroup resembles BED, with the exception of the presence of purging behaviors. The findings of the present study suggest the need to further investigate the exclusionary criteria of purging/compensatory behaviors for the BED diagnosis.


An automated technique to stage lower third molar development on panoramic radiographs for age estimation: a pilot study.
Automated methods to evaluate growth of hand and wrist bones on radiographs and magnetic resonance imaging have been developed. They can be applied to estimate age in children and subadults. Automated methods require the software to (1) recognise the region of interest in the image(s), (2) evaluate the degree of development and (3) correlate this to the age of the subject based on a reference population. For age estimation based on third molars an automated method for step (1) has been presented for 3D magnetic resonance imaging and is currently being optimised (Unterpirker et al. 2015). To develop an automated method for step (2) based on lower third molars on panoramic radiographs. A modified Demirjian staging technique including ten developmental stages was developed. Twenty panoramic radiographs per stage per gender were retrospectively selected for FDI element 38. Two observers decided in consensus about the stages. When necessary, a third observer acted as a referee to establish the reference stage for the considered third molar. This set of radiographs was used as training data for machine learning algorithms for automated staging. First, image contrast settings were optimised to evaluate the third molar of interest and a rectangular bounding box was placed around it in a standardised way using Adobe Photoshop CC 2017 software. This bounding box indicated the region of interest for the next step. Second, several machine learning algorithms available in MATLAB R2017a software were applied for automated stage recognition. Third, the classification performance was evaluated in a 5-fold cross-validation scenario, using different validation metrics (accuracy, Rank-N recognition rate, mean absolute difference, linear kappa coefficient). Transfer Learning as a type of Deep Learning Convolutional Neural Network approach outperformed all other tested approaches. Mean accuracy equalled 0.51, mean absolute difference was 0.6 stages and mean linearly weighted kappa was 0.82. The overall performance of the presented automated pilot technique to stage lower third molar development on panoramic radiographs was similar to staging by human observers. It will be further optimised in future research, since it represents a necessary step to achieve a fully automated dental age estimation method, which to date is not available.


Highly Efficient Microwave Absorption of Magnetic Nanospindle-Conductive Polymer Hybrids by Molecular Layer Deposition.
Oxidative molecular layer deposition (oMLD) was applied to fabricate conductive polymer-magnetic material core-shell microwave absorbers in this work. One dimensional Fe3O4-poly(3,4-ethylenedioxythiophene) (PEDOT) nanospindles with controllable PEDOT thickness were successfully synthesized. Their absorption performance was evaluated in the 2-18 GHz frequency range. With the advantage of oMLD, PEDOT shell thicknesses can be controlled precisely. Because the permittivity of Fe3O4-PEDOT nanospindles obviously increases while their permeability decreases slightly with the PEDOT cycles, the properties can be tuned effectively by only adjusting the PEDOT cycle number. With a proper PEDOT shell thickness, excellent reflection characteristics can be obtained. Remarkably high absorption strength (-55.0 dB at 16.2 GHz) and good absorption bandwidth (4.34 GHz less than -10 dB) were realized. Such excellent performance is better than that reported previously for most magnetic material-based absorbers. Considering the precise controllability and excellent absorption performance of the prepared microwave absorbers, we believe that oMLD is a facile synthetic route for microwave absorbers.


Clinical significance of mismatch repair gene expression in sporadic colorectal cancer.
Mismatch repair (MMR) genes play an important role in the occurrence and development of sporadic colorectal cancer; however, the effect of MMR genes on clinicopathological features and prognosis remains unclear. The aim of the present study was to observe the clinical significance of MMR gene expression in sporadic colorectal cancer. Clinicopathological data and postoperative samples from 404 patients with sporadic colorectal cancer were obtained from the Affiliated Tumor Hospital of Xinjiang Medical University. The immunohistochemistry PV-9000 two-step method was performed to measure the protein expression of human mutL homolog 1 (hMLH1), human mutS homolog (hMSH) 2, human postmeiotic segregation increased 2 (hPSM2) and hMSH6. Differences in clinicopathological features, family history and survival time subsequent to surgery between groups with normal and aberrant MMR protein (MMRP) expression were compared. A total of 27.23% of all patients showed aberrant nuclear staining of MMRP. Among the patients with aberrant MMRP expression, a higher proportion of patients showed aberrant expression of more than one type of MMRP than aberrant expression of only one type of MMRP. Aberrant expression of hMLH1/hPSM2 was most commonly observed (29/404). In addition, aberrant MMRP expression in colorectal cancer was indicated predominantly in the right hemicolon. Histological type primarily showed mucinous adenocarcinoma. In addition, with increasing body mass index (BMI), the MMRP deficiency rate was also shown to increase gradually. There was a close association between MMRP expression deficiency and family history of cancer (P<0.05). For TNM stage III patients, the Kaplan-Meier survival curve showed that the aberrant MMRP expression group had a three-year disease-free survival (DFS) rate of 66.67%, which was longer than the DFS rate of the normal group (55.41%), with no statistical difference (P>0.05). In conclusion, the immunohistochemistry PV-9000 two-step method can be used to measure MMRP expression in colorectal cancer. Aberrant MMRP expression is closely correlated with tumor location, histological type, BMI and tumor family history in sporadic colorectal cancer. Aberrant MMRP expression may have an effect on the prognosis of stage III patients.


The factor V Leiden mutation, high factor VIII, and high plasminogen activator inhibitor activity: etiologies for sporadic miscarriage.
We hypothesized that the thrombophilic G1691A factor V Leiden gene mutation was a common significant cause of sporadic first trimester miscarriage. We compared thrombophilia and hypofibrinolysis in 92 women (85 white, 5 black, 2 other) with 1 or more pregnancies and 1 miscarriage (143 live births, 92 miscarriages) (cases) and in 380 female controls (355 white, 21 black, 4 other) with 1 or more pregnancies and 0 miscarriages (964 live births). We used polymerase chain reaction techniques to characterize thrombophilic gene mutations (G1691A V Leiden [FV], G20210A prothrombin, C677T/A1298C MTHFR) and hypofibrinolytic gene mutations (plasminogen activator inhibitor [PAI-1] activity 4G4G). We carried out serologic measures of thrombophilia (homocysteine, anticardiolipin antibodies [ACLA] immunoglobulin G and immunoglobulin M, lupus anticoagulant, factor VIII, factor XI, protein C, total and free protein S, antithrombin III) and hypofibrinolysis (plasminogen activator inhibitor activity [PAI-Fx], lipoprotein[a]). Of the 380 controls, 6 (1.6%) had FV heterozygosity vs 12 heterozygous and 2 homozygous FV cases (15.2% [14/92]; P < .0001). Plasminogen activator inhibitor activity was high (> or =21.1 U/mL) in 21 (33%) of 63 cases vs 27 (18%) of 152 controls (P = .013). Factor VIII was high (>150%) in 15 (31%) of 48 cases vs 19 (18%) of 103 controls (P = .079). By logistic regression, with age and factor VIII (categorical [< or =150%, >150%]) as explanatory variables and group (cases, controls) as the dependent variable, after adjusting for age, high factor VIII was a significant predictor for miscarriage (odds ratio, 3.28; 95% confidence interval, 1.34-8.04; P = .01). There were no other group differences (P > .05) in measures of thrombophilia and hypofibrinolysis. After unexplained sporadic first trimester miscarriage, we suggest that measurements be done of the FV mutation, PAI-Fx, and factor VIII, etiologies for sporadic miscarriage.


Angiotensin II-induced endothelial dysfunction is temporally linked with increases in interleukin-6 and vascular macrophage accumulation.
Angiotensin II (Ang II) is associated with vascular hypertrophy, endothelial dysfunction and activation of a number of inflammatory molecules, however the linear events involved in the development of hypertension and endothelial dysfunction produced in response to Ang II are not well defined. The goal of this study was to examine the dose- and temporal-dependent development of endothelial dysfunction in response to Ang II. Blood pressure and responses of carotid arteries were examined in control (C57Bl/6) mice and in mice infused with 50, 100, 200, 400, or 1000 ng/kg/min Ang II for either 14 or 28 Days. Infusion of Ang II was associated with graded and marked increases in systolic blood pressure and plasma Ang II concentrations. While low doses of Ang II (i.e., 50 and 100 ng/kg/min) had little to no effect on blood pressure or endothelial function, high doses of Ang II (e.g., 1000 ng/kg/min) were associated with large increases in arterial pressure and marked impairment of endothelial function. In contrast, intermediate doses of Ang II (200 and 400 ng/kg/min) while initially having no effect on systolic blood pressure were associated with significant increases in pressure over time. Despite increasing blood pressure, 200 ng/kg/min had no effect on endothelial function, whereas 400 ng/kg/min produced modest impairment on Day 14 and marked impairment of endothelial function on Day 28. The degree of endothelial dysfunction produced by 400 and 1000 ng/kg/min Ang II was reflective of parallel increases in plasma IL-6 levels and vascular macrophage content, suggesting that increases in arterial blood pressure precede the development of endothelial dysfunction. These findings are important as they demonstrate that along with increases in arterial pressure that increases in IL-6 and vascular macrophage accumulation correlate with the impairment of endothelial function produced by Ang II.


Discrepancies in self- and informant-reports of personality pathology: Examining the DSM-5 Section III trait model.
A proposed feature of personality pathology involves disturbances in identity, of which a lack of insight is one such manifestation. From recommendations in the literature, one potential approach to assess and quantify such impairment and link it to personality pathology, would be to obtain self-reports and informant reports and subsequently index the degree personality pathology severity exacerbates self-other discrepancies. The current study examines the degree to which self-reports and informant reports of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Section III trait scores are discrepant (i.e., mean-level discrepancies and correlational accuracy), as well as whether general personality pathology severity moderates these characteristics. Target participants (N = 208) in an elevated-risk community sample completed the Personality Inventory for DSM-5 (PID-5), and knowledgeable informants rated targets using the informant version of the PID-5. General personality pathology severity was assessed via an aggregate of five-factor model personality disorder prototype scores derived from self-report, informant-report, and interview ratings. Mean-level discrepancies and correlational accuracy (and their moderation by general personality pathology) for PID-5 domains, facets, and personality disorder scores were subsequently examined. Results suggested that targets tended to mostly rate themselves only slightly lower than informants across all PID-5 scores (median dz = .21), and correlational accuracy across all PID-5 scores was moderate (median r = .34). Importantly, however, mean-level discrepancies increased as general personality pathology severity scores increased. Implications and future directions for the multimethod assessment of dimensional personality pathology are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


[Histamine-release: present data and practical interest (author's transl)].
Histamine remains the best known humoral marker of hypersensitivity phenomena. Stored in blood basophilic cells and mast cells this histamine can be released under the influence of an immunitary factor with humoral or cellular mediation or under the dependance of irritative factors either chemical or medicinal. The authors recall the innermost mechanism of the main stages of histamine-release: recognition of membrane receptors, multiple enzymatic activations, opening of calcic membrane pores, synthesis of unpreformed mediators (SRSa and PAF), finally granular extrusion with release of histamine and of numerous mediators, among which the neutrophil chemotactic factor, one of the main responsible ones of the late phase of hypersensitivity phenomena. The regulation of histamine release is mostly done by cyclic AMP and GMP and the membrane receptors H2. The test of histamine release on whole blood or on leucocypte suspension enables by the study of effect-dose curves to differentiate the histamine release mechanisms: bell shaped curve in the case of immunitary processus and ascending curve for an irrative phenomenon. Practically this test can be used for diagnosing drugs allergies, professional asthmas or to study the pharmacological activity of a drug.


Competition between spin density wave and charge density wave driven by interactions of spinful Haldane model on honeycomb lattices.
We investigate the interacting spinful Haldane model with on-site and nearest-neighbor repulsions on honeycomb lattices. Interactions drive spin-density and charge-density waves competing with each other. This competition enriches the phase diagram of the system greatly, where both topological and non-topological coexistence phases emerge with spin-density and charge-density wave orders. Moreover, the topological phase transition accompanied by the energy gap closure in coexistence phases is of third order. Finally, we study the topological properties consisting ofChernnumbers and edge states for different phases.


Dudawalamides A-D, Antiparasitic Cyclic Depsipeptides from the Marine Cyanobacterium Moorea producens.
A family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A-D (1-4), was isolated from a Papua New Guinean field collection of the cyanobacterium Moorea producens using bioassay-guided and spectroscopic approaches. The planar structures of dudawalamides A-D were determined by a combination of 1D and 2D NMR experiments and MS analysis, whereas the absolute configurations were determined by X-ray crystallography, modified Marfey's analysis, chiral-phase GCMS, and chiral-phase HPLC. Dudawalamides A-D possess a broad spectrum of antiparasitic activity with minimal mammalian cell cytotoxicity. Comparative analysis of the Dhoya-containing class of lipopeptides reveals intriguing structure-activity relationship features of these NRPS-PKS-derived metabolites and their derivatives.


Self-organization and progenitor targeting generate stable patterns in planarian regeneration.
During animal regeneration, cells must organize into discrete and functional systems. We show that self-organization, along with patterning cues, govern progenitor behavior in planarian regeneration. Surgical paradigms allowed the manipulation of planarian eye regeneration in predictable locations and numbers, generating alternative stable neuroanatomical states for wild-type animals with multiple functional ectopic eyes. We used animals with multiple ectopic eyes and eye transplantation to demonstrate that broad progenitor specification, combined with self-organization, allows anatomy maintenance during regeneration. We propose a model for regenerative progenitors involving (i) migratory targeting cues, (ii) self-organization into existing or regenerating eyes, and (iii) a broad zone, associated with coarse progenitor specification, in which eyes can be targeted by progenitors. These three properties help explain how tissues can be organized during regeneration.


Migration cues induce chromatin alterations.
Directed cell migration is a property central to multiple basic biological processes. Here, we show that directed cell migration is associated with global changes in the chromatin fiber. Polarized posttranslational changes in histone H1 along with a transient decrease in H1 mobility were detected in cells facing the scratch in a wound healing assay. In parallel to the changes in H1, the levels of the heterochromatin marker histone H3 lysine 9 tri-methylation were elevated. Interestingly, reduction of the chromatin-binding affinity of H1 altered the cell migration rates. Moreover, migration-associated changes in histone H1 were observed during nuclear motility in the simple multicellular organism Neurospora crassa. Our studies suggest that dynamic reorganization of the chromatin fiber is an early event in the cellular response to migration cues.


Effects of Emulsifier, Overrun and Dasher Speed on Ice Cream Microstructure and Melting Properties.
Ice cream is a multiphase frozen food containing ice crystals, air cells, fat globules, and partially coalesced fat globule clusters dispersed in an unfrozen serum phase (sugars, proteins, and stabilizers). This microstructure is responsible for ice cream's melting characteristics. By varying both formulation (emulsifier content and overrun) and processing conditions (dasher speed), the effects of different microstructural elements, particularly air cells and fat globule clusters, on ice cream melt-down properties were studied. Factors that caused an increase in shear stress within the freezer, namely increasing dasher speed and overrun, caused a decrease in air cell size and an increase in extent of fat destabilization. Increasing emulsifier content, especially of polysorbate 80, caused an increase in extent of fat destabilization. Both overrun and fat destabilization influenced drip-through rates. Ice creams with a combination of low overrun and low fat destabilization had the highest drip-through rates. Further, the amount of remnant foam left on the screen increased with reduced drip-through rates. These results provide a better understanding of the effects of microstructure components and their interactions on drip-through rate. Manipulating operating and formulation parameters in ice cream manufacture influences the microstructure (air cells, ice crystals, and fat globule clusters). This work provides guidance on which parameters have most effect on air cell size and fat globule cluster formation. Further, the structural characteristics that reduce melt-down rate were determined. Ice cream manufacturers will use these results to tailor their products for the desired quality attributes.


Delay in OnabotulinumtoxinA Treatment During the COVID-19 Pandemic-Perspectives from a Virus Hotspot.
The COVID-19 pandemic has undoubtedly changed our practice of medicine. With our collective resources and attention focused on caring for those afflicted with the disease, other medical conditions have temporarily but understandably faced constraint. For migraine patients who often require in-person visits for infusions and procedures, this has become particularly challenging. Here, we share our experience in navigating this exigency amidst a local surge of COVID-19.


Speed of Dog Adoption: Impact of Online Photo Traits.
The Internet has radically changed how dogs are advertised for adoption in the United States. This study was used to investigate how different characteristics in dogs' photos presented online affected the speed of their adoptions, as a proof of concept to encourage more research in this field. The study analyzed the 1st images of 468 adopted young and adult black dogs identified as Labrador Retriever mixed breeds across the United States. A subjective global measure of photo quality had the largest impact on time to adoption. Other photo traits that positively impacted adoption speed included direct canine eye contact with the camera, the dog standing up, the photo being appropriately sized, an outdoor photo location, and a nonblurry image. Photos taken in a cage, dogs wearing a bandana, dogs having a visible tongue, and some other traits had no effect on how fast the dogs were adopted. Improving the quality of online photos of dogs presented for adoption may speed up and possibly increase the number of adoptions, thereby providing a cheap and easy way to help fight the homeless companion animal population problem.


The safety and efficacy of ledipasvir/sofosbuvir for the treatment of a nosocomial outbreak of HCV in patients with significant cardiovascular disease.
There is an unmet need for interferon- and ribavirin-free treatment for chronic HCV infection in patients with comorbidities including cardiovascular disease (CVD). The aim of this study was to evaluate the rates of sustained virological response (SVR) and adverse events in a cohort of patients with nosocomially acquired HCV genotype-1b following 12 weeks of therapy with fixed-dose combination (FDC) ledipasvir/sofosbuvir (LDV/SOF). This is a prospective, single-centre, open-label study of five non-cirrhotic patients with HCV genotype-1b and significant comorbid CVD, conducted at the Massachusetts General Hospital. All patients were prescribed an FDC tablet (LDV 90 mg/SOF 400 mg) once daily for 12 weeks. Serial measurements of safety parameters, virology, host immune correlates and adherence were performed. The primary outcome was the proportion of patients with SVR (plasma HCV RNA level <25 IU/ml), 12 weeks after treatment completion (SVR12). All five patients (100%) achieved SVR12, with no episodes of on- or post-treatment relapse. The most commonly reported adverse events were gastrointestinal illness and upper respiratory viral-type illness. There were no serious adverse events or discontinuations of medication attributable to the study drug. Deep sequencing analysis revealed no baseline NS3, NS5A or NS5B resistance-associated variants. In this open-label, uncontrolled, pilot study enrolling patients with HCV genotype-1b and significant CVD, administration of a fixed-dose, oral combination of LDV and SOF for 12 weeks was associated with high rates of SVR and minimal adverse events. Larger prospective studies that also include patients with cirrhosis and prior treatment non-responders are necessary.


The exciting field of neuro-repair in multiple sclerosis: an interview with Sarah I Sheikh.
Sarah Isabel Sheikh speaks to Laura Dormer, Commissioning Editor: Sarah I Sheikh, MD, MSc, MRCP, is a Senior Medical Director in Late Stage Clinical Development at Biogen. Her current focus is on developing therapies for multiple sclerosis/neuroinflammation, remyelination and neuro-repair. Prior to Biogen, Dr Sheikh was an attending in Neurology at Brigham and Women's Hospital. She completed her internship at Massachusetts General Hospital and residency in Neurology and Neuromuscular fellowship at Massachusetts General Hospital and Brigham and Women's Hospital. She received her medical degree from Oxford University Medical School, and a Masters in cell physiology from Oxford University, Corpus Christi College. She is a member of the Royal College of Physicians, London.


Comparison of nurses and general caregivers' knowledge, attitude, and practice on medication administration process and their distress level in long-term care facilities across Penang, Kuala Lumpur, and Selangor of Malaysia.
Comparing nurses and general caregivers' knowledge, attitude, and practices (KAP) on medication administration process in long-term care (LTC) setting and an assessment of their stress, anxiety, and depression (SAD) level. A cross-sectional survey was conducted among nurses and general caregivers working in LTC using a validated questionnaire. Consisting of demographic characteristics (Section 1); 40 questions on KAP (Section 2); and assessment of Depression, Anxiety, and Stress Scale (DASS-21) (Section 3). 155 formally paid staffs in 26 LTC facilities were recruited. Nurses scored significantly higher in the knowledge section compared to caregivers (12.4 ± 1.7 vs. 4.5 ± 3.8; P < 0.001); better attitude (41.5 ± 4.8 vs. 30.8 ± 7.3; P < 0.001); and better practice (65.2 ± 8.5 vs. 40.3 ± 10.9; P < 0.001), respectively. SAD scores reveal that caregivers had significantly higher level of stress, anxiety, and depression compared to the nurses. General caregivers exhibit poorer knowledge on aspects pertaining to posology, appropriate methods of drug administration, and side effects of common drugs used by the elderly. Compared to nurses, the general caregivers also reported poorer medication administration practices; including not checking labels and expiry dates prior to administration, and not providing basic information about medication therapy to the residents. However, both nurses and general caregivers reported positive attitudes in their role as caregivers. They take pride and satisfaction in their occupation providing support to the elderly. General caregivers demonstrated lesser knowledge, poorer attitude, and practices towards medication administration processes, in addition to higher SAD score in LTC facilities.


Pyoderma gangrenosum complicating a permanent pacemaker implantation: a case report and literature review.
Pocket complications are common after cardiac implantable electronic device implantation. We report a rare case of pyoderma gangrenosum (PG) complicating a permanent pacemaker implantation, and the first literature review of 10 published cases. Five days after pacemaker implantation for heart failure and 2:1 atrioventricular block, a 93-year-old man had pain in the scar and bleeding on contact. Two days later, he had fever, inflammatory syndrome, and a necrotic 7-cm wound. The pacemaker was removed and he was started on antibiotics. Due to a lack of bacterial growth in samples, PG (a rare aseptic, destructive inflammatory cutaneous condition) was suspected, and histology was compatible with this diagnosis. High-dose corticosteroids vastly improved his condition within 1 week, and after 2 months of decreasing-dose corticosteroid therapy, complete healing and normalization of the inflammatory syndrome were observed. Pyoderma gangrenosum should be considered if there is aseptic skin ulceration that is not controlled by antibiotic treatment. The first-line treatment for PG is high-dose systemic corticosteroids.


Safety updates in novel therapeutics for pediatric rheumatic disease.
Biologics and novel targeted therapeutics have transformed the management of pediatric rheumatic diseases over the past two decades; however, questions about short-term and long-term safety remain. Safety data gathered from recent clinical trials, long-term extensions of prior trials, registries, and other real-world evidence are summarized here for biologics and novel therapeutics commonly prescribed for pediatric rheumatic diseases. With nearly 20 years of therapeutic experience, tumor necrosis inhibitors (TNFi) are generally well tolerated, although infections, malignancy, and development of new autoimmunity remain a concern. Risk of infections may be higher in IL-1 and IL-6 inhibitors, and lower in abatacept, compared with TNFi. Safety data for B-cell-targeted therapeutics and janus kinase inhibitors are emerging, but remain limited, especially in children. Biologic and novel targeted therapeutics offer a promising future for children with pediatric rheumatic disease. However, long-term safety data in children remain limited for several agents. With any therapeutic option, both short-term and long-term safety concerns must be weighed against individual clinical needs when choosing the optimal treatment for each child.


[Effects of murine bone marrow endothelial cells on the in vitro expansion of human cord blood hematopoietic progenitor cells].
To observe the effects of bone marrow endothelial cells on the expansion of human umbilical cord blood (UCB) hematopoietic progenitors in vitro. Bone marrow endothelial cells were cultured and the serum free conditioned media (ECM) were collected. CD34+ cells derived from human umbilical cord blood (UCB) were isolated by MiniMACS. Hematopoietic progenitor cells were assayed after culturing with ECM or co-culturing with endothelial cell layer (ECL) for 24 hours. The effects of conditioned medium of endothelial cells which were cultured with bFGF (bFGF-ECM) on the expansion of cord blood hematopoietic progenitors also were investigated. UCB hematopoietic progenitors were significantly expanded by adding ECM or co-cultured with ECL, and ECM cultures and ECL cultures showed similar expansion effect on early progenitor cells. The effect of bFGF-ECM on the expansion of UCB hematopoietic progenitors was significantly better than that of ECM. Murine bone marrow endothelial cells support the quantitative expansion of UCB hematopoietic progenitor cells in vitro.


Primary Sclerosing Cholangitis: Burden of Disease and Mortality Using Data from the National Rare Diseases Registry in Italy.
Introduction: Studies on the epidemiology of primary sclerosing cholangitis (PSC) are mainly based on tertiary referral centers; and are retrospective case series susceptible to selection bias. The aim of this study was to estimate incidence; survival and cause of mortality of PSC in Italy; using population-based data. Methods: Data collected from the National Rare Diseases Registry (RNMR) and the National Mortality Database (NMD) were integrated and analyzed. Results: We identified 502 PSC incident cases. The crude incidence rate between 2012 and 2014 was 0.10 per 100,000 individuals. Sixty percent were male; mean age at disease onset and at diagnosis were 33 and 37 years; respectively; highlighting a mean diagnostic delay of 4 years. The rate of interregional mobility was 12%. Ten-year survival was 92%. In 32% of cases the cause of death was biliary-related; 12% died of biliary or gallbladder cancer. Conclusions: For rare diseases such as PSC; population-based cohort's studies are of paramount importance. Incidence rates of PSC in Italy are markedly lower and survival much longer than the ones reported from tertiary; single-centre series. Moreover; the diagnostic delay and the patient interregional mobility highlights the need for increasing awareness on the disease and for resource reallocation among Italian regions within the National Health Service.


Differential expression of HMGA1 and HMGA2 in dermatofibroma and dermatofibrosarcoma protuberans: potential diagnostic applications, and comparison with histologic findings, CD34, and factor XIIIa immunoreactivity.
The histologic distinction of dermatofibrosarcoma protuberans (DFSP) and dermatofibroma (DF) may be difficult, especially in the case of DF extending into the subcutaneous fat (deep DF). CD34 and Factor XIIIa staining is commonly used in separating DF from DFSP, but is not always helpful. HMGA1 and HMGA2 genes, members of the high mobility group protein family genes, encode proteins that act as architectural transcription factors and are frequently dysregulated in a variety of benign or locally aggressive mesenchymal tumors. In this study, we evaluated the immunoreactivity of HMGA1 and HMGA2 in a series of DF and DFSP to determine the possible utility for these markers in the differential diagnosis of these two entities. Immunohistochemical stains were performed on paraffin-embedded tissues from 22 cases of DF, including 14 cases of deep DF and 14 cases of DFSP, using antibodies against HMGA1 and HMGA2. CD34 and Factor XIIIa immunoreactivity was also evaluated in these lesions and compared with the results of HMGA immunostaining. Immunopositivity for both HMGA1 and HMGA2 was seen in 21of 22 (96%) DFs, but in only 3 (21%) and 1 (7%) of 14 DFSPs, respectively. While 100% of DFSP stained for CD34, 36% of DF also labeled for CD34. The immunoreactivity of HMGA1 and HMGA2 in DF was generally strong and diffuse, in contrast to weak and focal staining seen in DFSP. The proportion of cases with positive immunoreactivity for both markers was significantly higher in DF and in deep DF than in DFSP (P < 0.001). We conclude that HMGA1 and HMGA2 expression can be used to distinguish DF from DFSP with a degree of accuracy that is fully equivalent to that of Factor XIIIa and CD34.


Sequential neurohumoral measurements in patients with congestive heart failure.
Patients with chronic congestive heart failure are known to have increased plasma norepinephrine and plasma renin activity. In order to evaluate neurohumoral changes over time, we measured plasma norepinephrine and plasma renin activity at baseline and sequentially during follow-up in 49 patients with chronic, stable congestive heart failure. All patients were treated with digitalis and diuretics. Converting enzyme inhibitor therapy was prescribed as adjunctive therapy in 22 patients, while 10 patients were taking hydralazine and/or isosorbide dinitrate, seven were taking prazosin, and 10 had no adjunctive therapy. Patients were divided into those taking converting enzyme inhibitors (group I, n = 22) and those not taking converting enzyme inhibitors (group II, n = 27). Group I was followed for a median (25th to 75th percentiles) of 24.3 (18 to 27.9) months, while group II was followed for 18.7 (11.9 to 36.5) months. Results indicate that patients in group I demonstrate a significant positive trend for rise in plasma norepinephrine of 11.7 pg/ml per month (7.8 to 15 pg/ml per month, 95% confidence interval). Patients in group II also demonstrated a significant positive trend in plasma norepinephrine over time of 6.6 pg/ml per month (2.2 to 11.1 pg/ml per month). Moreover, there was a progressive trend upward in plasma renin activity over time in group II (median 0.34 ng/ml/hr per month; range 0.13 to 0.54). The data indicate that there is a significant trend of neurohumoral activation over time in patients with chronic, clinically stable congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)


Hybrid Nanocomposite Solid Electrolytes (n-C4H9)4NBF4-MgO.
Hybrid nanocomposite materials Bu4NBF4-MgO were obtained using a nanocrystalline MgO with a specific surface area of 324 m2/g and the grains size of 5.1 nm. As a result of the strong adhesion, the salt transforms into an interface-stabilized amorphous state within the thin layer near the interface. The analysis of the DSC data allowed one to estimate the concentration and the thickness of this amorphous layer as 4.8 nm. The amorphous interface phase has an enhanced ionic conductivity. As a result, conductivity of the nanocomposite increases with the concentration of the amorphous phase and reaches 1.1 × 10-3 S/cm at 150 °C at a concentration of the MgO additive x = 0.90 corresponding to the maximum content of the amorphous phase. The conductivity of the nanocomposite is by three orders of magnitude higher than the conductivity of pure Bu4NBF4. The nanocomposites are electrochemically stable up to 2.5 V. At high concentrations of MgO when the total volume of the salt is small the composites become nano- and mesoporous.


Studies on psychrophilic bacteria in two lakes of different trophy.
The number of bacteria capable of growth at low temperatures in two lakes was found to be subject to considerable variation throughout the year although the changes were not correlated with changes in ambient temperature. A correlation was, however, observed between temperature and ratio of number of psychrophiles to "total" count. All of the psychrophilic bacteria isolated from the studied lakes were able to grow at temperatures below 0 degrees C. Microorganisms isolated from eutrophic lakes were characterized by more pronounced stenothermy than those isolated from lake with low tropic level. These bacteria represented a type resembling a type resembling obligatory or ,,true" psychrophiles. Most of the isolates belonged to the genus Pseudomonas and to the Flavobacterium--Cytophaga group.


Adenosine deaminase, dipeptidyl peptidase-IV activities and lipid peroxidation are increased in the saliva of obese young adult.
Obesity is the hallmark of the metabolic syndrome representing a major global health problem. It is considered a state of chronic inflammation with minimal exploration of salivary biomarkers. Thus, the intent of the present study was to assess the activities of salivary dipeptidyl peptidase IV (DPP-IV), adenosine deaminase (ADA) and lipid peroxidation in obese young and overweight young subjects. ADA, DPP-IV activities and lipid peroxidation were investigated in saliva, as well as insulin, glucose, HbA1c, HOMA and anthropometric measurements in 149 young adults, including 54 with normal weight, 27 overweight and 68 obese subjects. Salivary ADA and DPP-IV activities as well as lipid peroxidation were higher in patients with obesity compared to the normal weight group. Correlations between ADA/DPP-IV activities, lipid peroxidation/ADA activity, ADA activity/hip circumference and BMI/weight were observed. Our results indicate that the increase in the salivary ADA and DPP-IV activities as well as in the lipid peroxidation could be related of the regulation to various aspects of adipose tissue function and inflammatory obesity. It is suggested that these salivary biomarkers may be used as biochemical test in clinical abnormalities present in obesity, in the absence of oral inflammatory diseases.


Imposed Environmental Stresses Facilitate Cell-Free Nanoparticle Formation by Deinococcus radiodurans.
The biological synthesis of metal nanoparticles has been examined in a wide range of organisms, due to increased interest in green synthesis and environmental remediation applications involving heavy metal ion contamination. Deinococcus radiodurans is particularly attractive for environmental remediation involving metal reduction, due to its high levels of resistance to radiation and other environmental stresses. However, few studies have thoroughly examined the relationships between environmental stresses and the resulting effects on nanoparticle biosynthesis. In this work, we demonstrate cell-free nanoparticle production and study the effects of metal stressor concentrations and identity, temperature, pH, and oxygenation on the production of extracellular silver nanoparticles by D. radiodurans R1. We also report the synthesis of bimetallic silver and gold nanoparticles following the addition of a metal stressor (silver or gold), highlighting how production of these particles is enabled through the application of environmental stresses. Additionally, we found that both the morphology and size of monometallic and bimetallic nanoparticles were dependent on the environmental stresses imposed on the cells. The nanoparticles produced by D. radiodurans exhibited antimicrobial activity comparable to that of pure silver nanoparticles and displayed catalytic activity comparable to that of pure gold nanoparticles. Overall, we demonstrate that biosynthesized nanoparticle properties can be partially controlled through the tuning of applied environmental stresses, and we provide insight into how their application may affect nanoparticle production in D. radiodurans during bioremediation.IMPORTANCE Biosynthetic production of nanoparticles has recently gained prominence as a solution to rising concerns regarding increased bacterial resistance to antibiotics and a desire for environmentally friendly methods of bioremediation and chemical synthesis. To date, a range of organisms have been utilized for nanoparticle formation. The extremophile D. radiodurans, which can withstand significant environmental stresses and therefore is more robust for metal reduction applications, has yet to be exploited for this purpose. Thus, this work improves our understanding of the impact of environmental stresses on biogenic nanoparticle morphology and composition during metal reduction processes in this organism. This work also contributes to enhancing the controlled synthesis of nanoparticles with specific attributes and functions using biological systems.


Wives who outearn their husbands: a transitory or persistent phenomenon for couples?
In what percentage of married couples do wives outearn their husbands, and, moreover, how persistent are these patterns? This study systematically examined variation in point-in-time estimates across alternative measures of earnings, definitions of types of couples, and data sources and gauged the persistence of these patterns for a period of three calendar years using data from the 2000 Current Population Survey and the 1996-2000 Survey of Income and Program Participation. Among the findings are that in 19% to 30% of all married couples, wives have higher earnings than their husbands. In 60% of such couples, this arrangement persists over the three-year period; for the rest, this arrangement is transitory.


Patterns of insulin secretion and responsiveness in Wistar-Kyoto and spontaneously hypertensive rats.
An intravenous glucose tolerance test (IVGTT) was performed on 16 spontaneously hypertensive rats (SHR) and 15 Wistar-Kyoto rats (WKY) by challenging them with an intravenous glucose load of 0.125 g/100 g body weight. Serum glucose and insulin were measured at 0, 15, 30, 60, 120, and 240 min. In a second experiment, oral glucose tolerance testing (OGTT) was performed with a glucose load of 170 mg/100 g body weight. Serum glucose and insulin were measured at 0, 30, 60, 120, and 240 min. A third experiment examined in vivo insulin-stimulated peripheral glucose uptake via the insulin suppression test. Glucose (8 mg/kg/min), insulin (2.5 to 4.0 mU/kg/min), and somatostatin (1 ng/kg/min) were infused for 3 h. Steady state serum glucose (SSSG) and serum insulin (SSSI) were determined at 0, 140, 160, and 180 min. IVGTT data indicated that serum glucose values were significantly increased in the WKY compared to the SHR at 15, 30, 60, and 120 min. Glucose clearance rates between 15 and 60 min were significantly (P less than .0001) lower in WKY (0.65 +/- 0.07%/min) compared to SHR (1.91 +/- 0.17%/min). The SHR exhibited an exaggerated 15-min peak in insulin secretion that was lacking in the WKY in response to an intravenous glucose load. OGTT data also indicated that the area under the serum insulin curves was higher in the WKY than in the SHR (P less than .017). Peripheral insulin sensitivity showed that despite comparable SSSI levels between the two strains, SSSG values were 31% higher in the SHR compared to the WKY (P less than .001). Thus, it appears that the WKY has a diminished insulin secretory capacity in response to a glucose load, while the SHR has lower tissue responsiveness to insulin's action.


[Diagnostic and stating problems in delirium tremens cases].
To get to know the kinds and prevelence of diagnostic problems related to delirium tremens cases as well as their stating ramifications related to correctness of medical treatment. Twelve forensic psychiatric opinions of delirium tremens cases made in Adult Psychiatry Department of Medical University in Lodz in years 2002-2007 were assessed as far as correctness of medical treatment is concerned. In analyzed material of 12 delirium tremens patients no mistreatment cases were found. The most frequent reason of hospitalization was head trauma--7 cases (58%), among them 4 cases (33%) were the consequence of epileptic seizure. None of the patients was referred to psychiatric department and in most cases they were hospitalized in surgical wards--7 patients (58%) or neurological wards--4 patients (33%). During hospitalization in majority of patients--10 cases (83%) delirium tremens was observed on second day. 50% of patients were transferred to psychiatric wards. 11 (92%) of analised patients died. In all of the cases chronic alcoholism with delirium tremens accompanying as the one however indirect cause of death was revealed. The direct cause of death in all the cases was acute circulatory or circulatory and respiratory failure.


Synthesis, structural and magnetic properties of a series of copper(II) complexes containing a monocarboxylated perchlorotriphenylmethyl radical as a coordinating open-shell ligand.
A series of complexes of copper(II)-containing a perchlorotriphenylmethyl radical functionalized with a carboxylic group as a new ligand is reported. The compounds [Cu(PTMMC)(2)(L)(3)](PTMMC = (tetradecachloro-4-carboxytriphenyl)methyl radical; L =(1) H(2)O, (2) pyrimidine and ethanol or (3) pyridine), [Cu(2)(PTMMC)(2)(MeCOO)(2)(H(2)O)(2)](4) and [Cu(HPTMMC)(2)(L)(3)](HPTMMC =alpha-H-(tetradecachlorotriphenyl)methane-4-carboxylic acid; L = pyridine)(5) were structurally characterized. In complexes 1, 2, 3, and 5, the copper(II) ion is coordinated to two PTMMC (or HPTMMC) units in a slightly distorted square planar surrounding, while 4 shows a paddle-wheel copper(II) dimer structure, where each Cu metal ion has four O atoms of different carboxylate groups, two of them belonging to two PTMMC radicals. The copper(II)-radical exchange couplings are antiferromagnetic for complexes 1, 2 and 3. A linear three-spin model was applied to complexes 1, 2 and 3 to give J/k(B)=-24.9, -15.0 and -20.7 K, respectively. Magnetic properties of 4 show that it is one of the scarce examples of a spin-frustrated system composed of organic radicals and metal ions. In this case, experimental data were fitted to a magnetic model based on a symmetrical butterfly arrangement to give a copper(II)-copper(II) exchange coupling of J/k(B)=-350.0 K and a copper(II)-radical exchange coupling of J/k(B)=-21.3 K, similar to that observed for the copper(II)-radical interactions in complexes, and.


How evolution makes proteins fold quickly.
Sequences of fast-folding model proteins (48 residues long on a cubic lattice) were generated by an evolution-like selection toward fast folding. We find that fast-folding proteins exhibit a specific folding mechanism in which all transition state conformations share a smaller subset of common contacts (folding nucleus). Acceleration of folding was accompanied by dramatic strengthening of interactions in the folding nucleus whereas average energy of nonnucleus interactions remained largely unchanged. Furthermore, the residues involved in the nucleus are the most conserved ones within families of evolved sequences. Our results imply that for each protein structure there is a small number of conserved positions that are key determinants of fast folding into that structure. This conjecture was tested on two protein superfamilies: the first having the classical monophosphate binding fold (CMBF; 98 families) and the second having type-III repeat fold (47 families). For each superfamily, we discovered a few positions that exhibit very strong and statistically significant "conservatism of conservatism"-amino acids in those positions are conserved within every family whereas the actual types of amino acids varied from family to family. Those amino acids are in spatial contact with each other. The experimental data of Serrano and coworkers [Lopez-Hernandez, E. & Serrano, L. (1996) Fold. Des. (London) 1, 43-55]. for one of the proteins of the CMBF superfamily (CheY) show that residues identified this way indeed belong to the folding nucleus. Further analysis revealed deep connections between nucleation in CMBF proteins and their function.


Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C.
To evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older. The present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin (RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years (range: 28-65 years) in the younger group and 69 years (range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years (range: 36-65 years) in the younger group and 71 years (range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment. Among the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response (SVR) was found between the younger (80.8%) and older (88.2%) groups. The SVR rates for patients with the interleukin 28B (IL28B) (rs8099917) TG/GG-genotypes (73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period (as a percentage of the target dose) was significantly higher in the younger group than in the older group (91.7% vs 66.7%, respectively, P < 0.01), but the cumulative exposure to TVR was not significantly different between the younger and older groups (91.6% vs 81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28B (OR = 8.160; 95%CI: 1.593-41.804, P = 0.012) and the adherence of RBV (> 60%) (OR = 11.052; 95%CI: 1.160-105.273, P = 0.037) as independent factors associated with the SVR. Adverse events resulted in discontinuation of the treatment in 11.3% and 14.7% of the younger and older groups, respectively. Among the patients treated with the SMV-based triple therapy, no significant difference in the SVR rare was found between the younger (81.1%) and older (82.1%) groups. The SVR rates for patients with the IL28B TG/GG-genotypes (77.8% and 64.7% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (88.2% and 100%, respectively). A multivariate analysis identified the TT-genotype of IL28B as an independent factor associated with the SVR (OR = 9.677; 95%CI: 1.114-84.087, P = 0.040). Adverse events resulted in discontinuation of the treatment in 7.0% and 14.3% of patients in the younger and older groups, respectively. Both TVR- and SMV-based triple therapies can be successfully used to treat patients aged 66 years or older with genotype 1b chronic hepatitis C. Genotyping of the IL28B indicates a potential to achieve SVR in these difficult-to-treat elderly patients.


Improvement of bowel movements among people with a sedentary lifestyle after prebiotic snack supply - preliminary study.
Dietary fiber is one of the most important components of food. Fulfilling regulatory and nutritional functions for the intestinal microbiota, it appears to be an essential ingredient for people with a sedentary lifestyle. We hypothesized that regular intake of a snack containing high amounts of soluble fibre in parallel to a regular diet may rapidly improve bowel habits with simultaneous elevation of synthesis of short-chain fatty acids (SCFA). A total of 20 healthy volunteers, with a stool frequency of less than 3 spontaneous bowel movements per week, completed a 14-day double-blind, parallel-arm, randomized clinical trial with the intervention comprising daily intake of 2 doses (9.99% per 100 g or 13.91% per 100 g) of fibre. Food consumption was evaluated via 72-hour recall diaries at baseline and after 14 days of intervention. Gastrointestinal symptoms (abdominal comfort, distension, bloating, flatulence, stomach rumbling, number of bowel movements) were monitored via the IBS/VAS scale every day. We found that the elevated fibre intake improved bowel habits significantly (defecation frequency increased from 0.28 to 0.87 times/day; p = 0.0002) in both study arms. After 14 days of the trial, an increase in SCFA concentration (for whole study group: acetic p < 0.036, propionic p < 0.019, and butyric acid p < 0.0012 compared to baseline parameters) with no adverse gastrointestinal symptoms was reported. Short-term, regular intake of a snack containing soluble fibre improves the SCFA synthesis and bowel habits in healthy people living a sedentary lifestyle. The exact mechanism behind this observation requires further investigation.


Adaptation and promotion of emergency medical service transportation for climate change.
The purpose of this study is to find a proper prehospital transportation scenario planning of an emergency medical service (EMS) system for possible burdensome casualties resulting from extreme climate events. This project focuses on one of the worst natural catastrophic events in Taiwan, the 88 Wind-caused Disasters, caused by the Typhoon Morakot; the case of the EMS transportation in the Xiaolin village is reviewed and analyzed. The sequential-conveyance method is designed to promote the efficiency of all the ambulance services related to transportation time and distance. Initially, a proposed mobile emergency medical center (MEMC) is constructed in a safe location near the area of the disaster. The ambulances are classified into 2 categories: the first-line ambulances, which reciprocate between the MEMC and the disaster area to save time and shorten the working distances and the second-line ambulances, which transfer patients in critical condition from the MEMC to the requested hospitals for further treatment. According to the results, the sequential-conveyance method is more efficient than the conventional method for EMS transportation in a mass-casualty incident (MCI). This method improves the time efficiency by 52.15% and the distance efficiency by 56.02%. This case study concentrates on Xiaolin, a mountain village, which was heavily destroyed by a devastating mudslide during the Typhoon Morakot. The sequential-conveyance method for the EMS transportation in this research is not only more advantageous but also more rational in adaptation to climate change. Therefore, the findings are also important to all the decision-making with respect to a promoted EMS transportation, especially in an MCI.


Family practice incidence rates.
It is difficult for practicing physicians to understand the annual incidence of disease in terms that are directly relevant to their practices. A simple calculation, called the family practice incidence rate (FPIR), has been developed to assist family physicians in applying epidemiological information to their own patient population. By multiplying the annual incidence of a disease by the practice panel size and dividing by the population, it is possible to determine the number of cases a family physician will see in 1 year. When the answer is a fraction, that fraction can be divided into 1 year to determine the number of years required to encounter one case. This formula can be adjusted for panel size, specific percentages of the practice panel and regional variations in incidence rates. The FPIR is a convenient model to make the incidence of disease, mortality data, and demographic data immediately available to the practicing physician. Using this calculation will help physicians better understand the patient population they serve.


Prediction and characterization of the linear IgE epitopes for the major soybean allergen β-conglycinin using immunoinformatics tools.
The α subunit of β-conglycinin is a major allergen in soybean. The objective of this study was to predict and identify the linear immunoglobulin (Ig)E epitopes of the soybean α subunit of β-conglycinin. Three immunoinformatics tools were used to predict the potential epitopes and were confirmed by dot-blot inhibition using sera from soybean allergic subjects. As a result, 15 peptides were predicted and assembled by solid-phase synthesis. Eleven epitopes were identified by the dot-blot inhibition test. Moreover, peptide 3 had IgE binding capability with all sera(5/5) tested, while peptide 1, 4, 6, 8 and12 could bind to 4/5 of the sera samples. Secondary structure prediction of peptide 3 and circular dichroism test validated that the structure of peptide 3 was a random coil.


Charge exchange recombination spectroscopy measurements of DIII-D poloidal rotation with poloidal asymmetry in angular rotation.
Sixteen new tangential views for the charge exchange recombination (CER) spectroscopy diagnostic at DIII-D were installed in 2019 on the high-field side (HFS) of the tokamak with the main goal being the measurement of main-ion (deuterium) poloidal rotation. Eight of the new views are connected to spectrometers, which view the main-ion spectrum, adding main-ion measurements where there were previously none, and another eight new views increased the spatial resolution of existing impurity (carbon) measurements on the HFS. When combined with the existing low-field side measurements, measurements at two locations on flux surfaces out to a normalized minor radius of ≈0.6 are possible. The new tangential views have been used to measure the deuterium poloidal rotation directly for the first time using the Poloidal Asymmetry in Angular Rotation (PAAR) method. These new measurements enable further testing of the validity of neoclassical poloidal rotation predictions. Separate measurements of the radial electric field can be made for an impurity ion and the main-ion by combining the PAAR measurements with additional CER measurements of toroidal rotation, temperature, and density. These independent measurements of the radial electric field agree reasonably well.


The future is now! Five steps for making it happen.
In today's market, dentists need to be open to using different approaches for increasing patient awareness of how dentistry can benefit them. The five key areas of practice management addressed here are just a few of the many ways to keep your practice healthy in our changing profession. Dentists who are committed to improving patient communication and accommodating the needs of their patients will be the ones for whom the future is bright.


Albuterol HFA is as effective as albuterol CFC in preventing exercise-induced bronchoconstriction.
Secondary to the phase-out of chlorofluorocarbons (CFCs), the albuterol (Ventolin, GlaxoSmithKline, Uxbridge, Middlesex, United Kingdom) pressurized metered-dose inhaler (MDI) has been formulated in a non-ozone-depleting propellant, hydrofluoroalkane (HFA) 134a. To compare the efficacy of albuterol HFA to albuterol CFC and placebo HFA in protecting patients from exercise-induced bronchospasm (EIB). Randomized, double-blind, placebo-controlled, three-way crossover study in patients with documented EIB. Patients (n = 24) aged 18 to 45 years old received albuterol HFA or albuterol CFC, (total dose of 180 microg ex-actuator), or placebo HFA via an MDI, 30 minutes before a standardized exercise challenge. Serial forced expiratory volume in 1 second (FEV1) measurements were made 5 minutes before exercise and 5, 10, 15, 20, 25, 30, and 60 minutes postexercise. The primary outcome measure was the maximum percentage fall in FEV1 over the 60 minutes after exercise. The adjusted mean maximum percentage falls in FEV1 postexercise for albuterol HFA and CFC groups were 15.4% and 14.9%, respectively. The two formulations were comparable with a treatment difference of -0.5% (P = 0.848; 95% confidence interval, -5.3 to 4.4%). When compared with the fall in FEV1 for placebo (33.7%), both active treatments demonstrated a significantly smaller fall in FEV1 postexercise (P < 0.001). Safety profiles were similar among the three treatment groups. The results provide assurance to prescribers that the formulation of albuterol in the non-ozone-depleting propellant HFA 134a has not affected its efficacy in the treatment of EIB in asthmatic patients. Single doses of albuterol HFA and CFC from an MDI are comparable in terms of efficacy and safety on a microgram per microgram basis.


Occlusion and facial pain.
The role of the occlusion in the aetiology of reflex jaw muscle hyperactivity and myofacial pain is analysed. Neurological mechanisms are proposed to explain how variations in occlusal morphology of sufficient magnitude (segmental influences), and the presence of anxiety states (suprasegmental influences) affect jaw muscle activity and contribute to myofascial pain. Controlled occlusal therapy may alter the segmental neurological control of jaw muscle activity to facilitate resolution of muscle hyperactivity in acute myofascial pain. Chronic myofascial pain dysfunction is not primarily related to occlusal factors and a complex psychophysiological mechanism is involved in this type of pain problem.


Treatment with secukinumab for plaque psoriasis in patients with infectious comorbidities and latent tuberculosis: A multi-case report analysis.
Three patients affected by plaque psoriasis and presenting with multiple infectious comorbidities and latent tuberculosis infection (LTBI) were initially managed with conventional DMARD therapy. After showing unsuccessful results, treatment with secukinumab was initiated without prophylactic isoniazid and soon led to favorable dermatological outcomes without the reactivation of tuberculosis infection.


AVLINE: a data base and critical review system of audiovisual materials for the education of health professionals.
The AVLINE data base, operated by the National Library of Medicine, was designed to aid in the selection, use, and sharing of quality audiovisual material in the education of health professionals and to promote the quality production of such materials. AVLINE provides standardized bibliographic and critical review information in both online and printed catalog form. In this report the evolution of AVLINE is traced, and the development of its companion review system is examined.


Rapid synthesis of quinoline-4-carboxylic acid derivatives from arylimines and 2-substituted acrylates or acrylamides under indium(III) chloride and microwave activations. Scope and limitations of the reaction.
Rapid synthesis of quinoline-4-carboxylic acid derivatives has been achieved by reaction of 2-methoxy acrylates or acrylamides with N-arylbenzaldimines in acetonitrile under InCl3 catalysis and microwave irradiation. Isolated yields up to 57% within 3 min have been obtained. The Lewis acid and the microwave activation appeared as crucial parameters for the reaction. The role of indium chloride and ytterbium triflate was specified using 13C NMR data and model theoretical studies.


Slow photoelectron velocity-map imaging of cold tert-butyl peroxide.
Photoelectron spectra of cryogenically cooled X∼1A' tert-butyl peroxide anions are obtained using slow electron velocity-map imaging. The spectra show highly structured bands corresponding to detachment to the X∼2A″ and A∼2A' electronic states of the neutral radical and represent a notable improvement in resolution over previous photoelectron spectra. We report an electron affinity of 1.1962(20) eV and a term energy T0(A∼2A') of 0.9602(24) eV for the tert-butyl peroxy radical. New vibrational structure is resolved, providing several frequencies for both neutral states. Additionally, the threshold behavior of the photodetachment cross section is investigated within the context of Dyson orbital calculations.


Tuberculosis and illicit drug use: review and update.
Illicit drug users continue to be a group at high risk for tuberculosis (TB). Here, we present an updated review of the relationship between TB and illicit drug use, and we summarize more than a decade of new research. Drug users, and injection drug users in particular, have driven TB epidemics in a number of countries. The successful identification and treatment of TB among illicit drug users remain important components of a comprehensive TB strategy, but illicit drug users present a unique set of challenges for TB diagnosis and control. New diagnostic modalities, including interferon-gamma-release assays, offer potential for improved diagnosis and surveillance among this group, along with proven treatment strategies that incorporate the use of directly observed therapy with treatment for drug abuse. Special considerations, including coinfection with viral hepatitis and the rifampin-methadone drug interaction, warrant clinical attention and are also updated here.


Detection of various types of resistance patterns and their correlation with minimal inhibitory concentrations against clindamycin among methicillin-resistant Staphylococcus aureus isolates.
The macrolide lincosamide streptogramin B (MLS B ) family of antibiotics serves as an alternative for the treatment of skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, resistance to clindamycin too has emerged, which is of two types, inducible and constitutive. Therapeutic failure is common with inducible type of clindamycin resistance. This study was done to determine the various clindamycin resistance patterns in MRSA isolates and to compare them with minimal inhibitory concentration (MIC) of clindamycin. Fifty MRSA isolates were studied by disc approximation test (D test) to detect inducible iMLS B resistance and MIC by agar dilution technique. Of the 50 isolates, 34 were sensitive to both clindamycin and erythromycin. 16 isolates showed different sensitivity patterns; nine of these were positive for D zone indicating inducible iMLS B resistance, five were positive for constitutive MLS B resistance and two showed possible efflux mechanism for macrolide resistance. Out of the 34 sensitive isolates, 5 showed isolated colonies (subpopulation) inside the clindamycin-sensitive zone. When these sub-populations were tested further, two were constitutive MLS B phenotypes, two were inducible iMLS B and one was HD (hazy D zone), which is D + with growth up to clindamycin disc (which is also considered as constitutive MLS B phenotype). Seven isolates showed an MIC of ≥4 μg/ml to clindamycin in spite of being susceptible to both erythromycin and clindamycin by Kirby Bauer disc diffusion technique. Out of these seven isolates, five were those which grew as subpopulation inside the clindamycin-sensitive zone. Detection of iMLS B resistance among MRSA helps to avoid treatment failure with clindamycin. Studying the subpopulation inside the clindamycin-sensitive zone raises the question of existence of hetero-resistance or some other mechanism, which needs further study.


Emotion perception and empathy: An individual differences test of relations.
Numerous theories posit a positive relation between perceiving emotion expressed in the face of a stranger (emotion perception) and feeling or cognitively understanding the emotion of that person (affective and cognitive empathy, respectively). However, when relating individual differences in emotion perception with individual differences in affective or cognitive empathy, effect sizes are contradictory, but often not significantly different from zero. Based on 4 studies (study ns range from 97 to 486 persons; ntotal = 958) that differ from one another on many design and sample characteristics, applying advanced modeling techniques to control for measurement error, we estimate relations between affective empathy, cognitive empathy, and emotion perception. Relations are tested separately for each of the 6 basic emotions (an emotion-specific model) as well as across all emotions (an emotion-general model). Reflecting the literature, effect sizes and statistical significance with an emotion-general model vary across the individual studies (rs range from -.001 to .24 for emotion perception with affective empathy and -.01 to .39 for emotion perception with cognitive empathy), with a meta-analysis of these results indicating emotion perception is weakly related with affective (r = .13, p = .003) and cognitive empathy (r = .13, p = .05). Relations are not strengthened in an emotion-specific model. We argue that the weak effect sizes and inconsistency across studies reflects a neglected distinction of measurement approach-specifically, empathy is assessed as typical behavior and emotion perception is assessed as maximal effort-and conclude with considerations regarding the measurement of each construct. (PsycINFO Database Record


Inhibition of phorbol ester-induced PGF2alpha secretion by IFN-tau is not through regulation of protein kinase C.
Inhibitory effect of IFN-tau on phorbol ester (PdBu)-induced PGF2alpha secretion was hypothesized to be manifested by the regulation of protein kinase C (PKC) in bovine endometrial (BEND) cells. Following 12 h stimulation with PdBu, cells were unresponsive to freshly added PdBu. Pretreatment of cells with a PKC inhibitor abolished PGF2alpha secretion in response to PdBu. Therefore, PdBu induction of PGF2alpha secretion is through activation of PKC. The alpha, epsilon, iota and lambda isotypes of the PKC family were identified by Western blotting. Cells were then treated with medium alone (control), PdBu or PdBu + IFN-tau for 3 or 6 h. The PdBu-induced secretion of PGF2alpha was suppressed by IFN-tau. At 3 and 6 h, PKCalpha and PKCepsilon were detected both in the cytosolic and membrane fractions of unstimulated cells. There was a clear reduction of PKCalpha in the cytoplasm induced by PdBu and PdBu + IFN-tau at 3 and 6 h. The total abundance (cytoplasm and membrane fractions) of PKCalpha was lower in the PdBu + IFN-tau than PdBu alone. These temporal responses indicate a PKCalpha responsiveness of BEND cells to PdBu and PDBu + INF-tau with some evidence that IFN-tau causes a slight but detectable reduction in PKCalpha when added with PdBu. However, IFN-tau-induced decrease in the total abundance of PKCalpha was not enough to affect negatively the translocation of the PKCalpha to the membrane. Therefore, IFN-tau's ability to suppress secretion of PGF2alpha is unlikely due to an interference with the PdBu-induced activity of PKC.


Aggregation-prone TDP-43 sequesters and drives pathological transitions of free nuclear TDP-43.
Aggregation of the RNA-binding protein, TDP-43, is the unifying hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. TDP-43-related neurodegeneration involves multiple changes to normal physiological TDP-43, which undergoes nuclear depletion, cytoplasmic mislocalisation, post-translational modification, and aberrant liquid-liquid phase separation, preceding inclusion formation. Along with toxic cytoplasmic aggregation, concurrent depletion and dysfunction of normal nuclear TDP-43 in cells with TDP-43 pathology is likely a key potentiator of neurodegeneration, but is not well understood. To define processes driving TDP-43 dysfunction, we used CRISPR/Cas9-mediated fluorescent tagging to investigate how disease-associated stressors and pathological TDP-43 alter abundance, localisation, self-assembly, aggregation, solubility, and mobility dynamics of normal nuclear TDP-43 over time in live cells. Oxidative stress stimulated liquid-liquid phase separation of endogenous TDP-43 into droplet-like puncta, or spherical shell-like anisosomes. Further, nuclear RNA-binding-ablated or acetylation-mimicking TDP-43 readily sequestered and depleted free normal nuclear TDP-43 into dynamic anisosomes, in which recruited endogenous TDP-43 proteins remained soluble and highly mobile. Large, phosphorylated inclusions formed by nuclear or cytoplasmic aggregation-prone TDP-43 mutants also caused sequestration, but rendered endogenous TDP-43 immobile and insoluble, indicating pathological transition. These findings suggest that RNA-binding deficiency and post-translational modifications including acetylation exacerbate TDP-43 aggregation and dysfunction by driving sequestration, mislocalisation, and depletion of normal nuclear TDP-43 in neurodegenerative diseases.


Partial purification of mitochondrial DNA topoisomerase II from Plasmodium falciparum and its sensitivity to inhibitors.
Mitochondria of Plasmodium falciparum (K1 strain) were isolated by differential centrifugation. Mitochondrial DNA topoisomerase II from P. falciparum was partially purified using fast protein liquid chromatography(FPLC). Parasite mitochondria contained approximately 8% of DNA topoisomerase II activity compared with its nuclear fraction. The effects of fluoroquinolones, inhibitors of bacterial DNA topoisomerase II or DNA gyrase, against partially purified P. falciparum mitochondrial DNA topoisomerase II were investigated using a decatenation assay. Minimum inhibitory concentrations (MIC) of ofloxacin, ciprofloxacin and norfloxacin were > 1, 10 and 100 mM, compared with that of >0.5 and 10 mM for eukaryotic DNA topoisomerase II inhibitor etoposide (VP-16) and amsacrine, respectively. The results indicate that partially purified mitochondrial DNA topoisomerase II was insensitive to fluoroquinolones and it is suggested that their inhibitory effects on P. falciparum growth may be directed against plastid DNA topoisomerase II.


Dual-mode fluorophore-doped nickel nitrilotriacetic acid-modified silica nanoparticles combine histidine-tagged protein purification with site-specific fluorophore labeling.
We present the first example of a fluorophore-doped nickel chelate surface-modified silica nanoparticle that functions in a dual mode, combining histidine-tagged protein purification with site-specific fluorophore labeling. Tetramethylrhodamine (TMR)-doped silica nanoparticles, estimated to contain 700-900 TMRs per ca. 23 nm particle, were surface modified with nitrilotriacetic acid (NTA), producing TMR-SiO2-NTA-Ni2+. Silica-embedded TMR retains very high quantum yield, is resistant to quenching by buffer components, and is modestly quenched and only to a certain depth (ca. 2 nm) by surface-attached Ni2+. When exposed to a bacterial lysate containing estrogen receptor alpha ligand binding domain (ERalpha) as a minor component, these beads showed very high specificity binding, enabling protein purification in one step. The capacity and specificity of these beads for binding a his-tagged protein were characterized by electrophoresis, radiometric counting, and MALDI-TOF MS. ERalpha, bound to TMR-SiO2-NTA-Ni++ beads in a site-specific manner, exhibited good activity for ligand binding and for ligand-induced binding to coactivators in solution FRET experiments and protein microarray fluorometric and FRET assays. This dual-mode type TMR-SiO2-NTA-Ni2+ system represents a powerful combination of one-step histidine-tagged protein purification and site-specific labeling with multiple fluorophore species.


A high carbohydrate, but not fat or protein meal attenuates postprandial ghrelin, PYY and GLP-1 responses in Chinese men.
It is known that the macronutrient content of a meal has different impacts on the postprandial satiety and appetite hormonal responses. Whether obesity interacts with such nutrient-dependent responses is not well characterized. We examined the postprandial appetite and satiety hormonal responses after a high-protein (HP), high-carbohydrate (HC), or high-fat (HF) mixed meal. This was a randomized cross-over study of 9 lean insulin-sensitive (mean±SEM HOMA-IR 0.83±0.10) and 9 obese insulin-resistant (HOMA-IR 4.34±0.41) young (age 21-40 years), normoglycaemic Chinese men. We measured fasting and postprandial plasma concentration of glucose, insulin, active glucagon-like peptide-1 (GLP-1), total peptide-YY (PYY), and acyl-ghrelin in response to HP, HF, or HC meals. Overall postprandial plasma insulin response was more robust in the lean compared to obese subjects. The postprandial GLP-1 response after HF or HP meal was higher than HC meal in both lean and obese subjects. In obese subjects, HF meal induced higher response in postprandial PYY compared to HC meal. HP and HF meals also suppressed ghrelin greater compared to HC meal in the obese than lean subjects. In conclusion, a high-protein or high-fat meal induces a more favorable postprandial satiety and appetite hormonal response than a high-carbohydrate meal in obese insulin-resistant subjects.


Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds.
CYP2A6 is a human enzyme responsible for the metabolic elimination of nicotine, and it is also involved in the activation of procarcinogenic nitrosamines, especially those present in tobacco smoke. Several investigations have reported that reducing this enzyme activity may contribute to anti-smoking therapy as well as reducing the risk of promutagens in the body. For these reasons, several authors investigate selective inhibitors molecules toward this enzyme. The aim of this study was to evaluate the interactions between a set of organosulfur compounds and the CYP2A6 enzyme by a quantitative structure-activity relationship (QSAR) analysis. The present work provides a better understanding of the mechanisms involved, with the final goal of providing information for the future design of CYP2A6 inhibitors based on dietary compounds. The reported activity data were modeled by means of multiple regression analysis (MLR) and partial least-squares (PLS) techniques. The results indicate that hydrophobic and steric factors govern the union, while electronic factors are strongly involved in the case of monosulfides.


[Autoantibodies against a 58 kD protein in neutropenia and NK cell deficiency].
An autoantibody against a 58 kD protein on granulocytes, activated NK cells and a subpopulation of B cells was detected in a patient with neutropenia and NK cell deficiency. The patient suffered from recurrent mucocutaneous candidosis and pharyngitis. After 18 months, a spontaneous remission of neutropenia and NK cell deficiency was observed, the autoantibody disappeared from the serum.


Diffusion-weighted imaging complements T2-weighted MRI for tumour response assessment in squamous anal carcinoma.
A published tumour regression grade (TRG) score for squamous anal carcinoma treated with definitive chemoradiotherapy based on T2-weighted MRI yields a high proportion of indeterminate responses (TRG-3). We investigate whether the addition of diffusion-weighted imaging (DWI) improves tumour response assessment in the early post treatment period. This retrospective observational study included squamous anal carcinoma patients undergoing MRI before and within 3 months of completing chemoradiotherapy from 2009 to 2020. Four independent radiologists (1-20 years' experience) scored MRI studies using a 5-point TRG system (1 = complete response; 5 = no response) based on T2-weighted sequences alone, and then after a 12-week washout period, using a 5-point DWI-TRG system based on T2-weighted and DWI. Scoring confidence was recorded on a 5-point scale (1 = low; 5 = high) for each reading and compared using the Wilcoxon test. Indeterminate scores (TRG-3) from each reading session were compared using the McNemar test. Interobserver agreement was assessed using kappa statistics. Eighty-five patients were included (mean age, 59 years ± 12 [SD]; 55 women). T2-weighted TRG-3 scores from all readers combined halved from 24% (82/340) to 12% (41/340) with DWI (p < 0.001). TRG-3 scores changed most frequently (41%, 34/82) to DWI-TRG-2 (excellent response). Complete tumour response was recorded clinically in 77/85 patients (91%). Scoring confidence increased using DWI (p < 0.001), with scores of 4 or 5 in 84% (287/340). Interobserver agreement remained fair to moderate (kappa range, 0.28-0.58). DWI complements T2-weighted MRI by reducing the number of indeterminate tumour responses (TRG-3). DWI increases radiologist's scoring confidence. Diffusion-weighted imaging improves T2-weighted tumour response assessment in squamous anal cancer, halving the number of indeterminate responses in the early post treatment period, and increases radiologists' confidence. Tumour response based on T2-weighted MRI is often indeterminate in squamous anal carcinoma. Diffusion-weighted imaging alongside T2-weighted MRI halved indeterminate tumour regression grade scores assigned by four radiologists from 24 to 12%. Scoring confidence of expert and non-expert radiologists increased with the inclusion of diffusion-weighted imaging.


[Association of polymorphisms in genes of osteoclastogenesis-related cytokines with severity in patients with rheumatoid arthritis].
The development or radiographic progression of rheumatoid arthritis (RA) is associated with HLA-DRB1 alleles encoding a conserved amino acid sequence commonly called the shared epitope(SE). Besides HLA-DRB1, however, other genes may be implicated in the progression of RA. On the other hand, osteoclasts play an important role in the joint destruction in patients with RA. Thus, it is speculated that polymorphisms in genes of cytokines which stimulate or inhibit osteoclastogenesis are associated with severity of RA. In fact, it has been reported that polymorphisms in genes of osteoclastogenesis-related cytokines are associated with the severity or radiographic progression of RA. In this article, we review recent findings, including ours, indicating that polymorphisms in genes of osteoclastogenesis-related cytokines may account for the severity of RA.


Preparation of a low viscosity urethane-based composite for improved dental restoratives.
Several new urethane-based dimethacrylates were synthesized, characterized and used to formulate the resin composites. Compressive strength (CS) was used as a screen tool to evaluate the mechanical property of the formed composites. Flexural strength, diametral tensile strength, water sorption, degree of conversion and shrinkage of the composites were also evaluated. The results show that most of the synthesized urethane-based dimethacrylates were solid, which are not suitable to dental filling restorations. However, it was found that liquid urethane-based dimethacrylates could be derivatized using asymmetrical methacrylate synthesis. Not only the newly synthesized urethane-based dimethacrylates showed lower viscosity values but also their constructed composites exhibited higher mechanical strengths. Without triethyleneglycol dimethacrylate (TEGDMA) addition, the new urethane-constructed composites showed significantly lower water sorption and shrinkage.


Study on TCM Syndrome Identification Modes of Coronary Heart Disease Based on Data Mining.
Coronary heart disease (CHD) is one of the most important types of heart disease because of its high incidence and high mortality. TCM has played an important role in the treatment of CHD. Syndrome differentiation based on information from traditional four diagnostic methods has met challenges and questions with the rapid development and wide application of system biology. In this paper, methods of complex network and CHAID decision tree were applied to identify the TCM core syndromes of patients with CHD, and to establish TCM syndrome identification modes of CHD based on biological parameters. At the same time, external validation modes were also constructed to confirm the identification modes.


Strongly emitting, centrosymmetric, ladder-type bis-coumarins with crankshaft architecture.
Quadrupolar bis-coumarins bearing dialkylamino groups, prepared by a double Pechmann reaction and subsequent oxidation, strongly emit yellow-orange light. Comparison with non-substituted analogs reveals that, the photophysical properties of the conjugated bis-coumarins are controlled both by the dialkylamino substituents and by the π-system. Analogous but non-conjugated bis-coumarins emit blue light both in solution and in crystalline state. Unusually fast oxidation process in the crystalline state is responsible for the presence of two bands in their solid-state emission. Two-center, charge-transfer transition from an orbital delocalized on the entire molecule to the central benzene ring is responsible for photophysical properties.


Antiproteinase 3 Positive Eosinophilic Granulomatosis with Polyangiitis Presenting with Heart Failure and Intraventricular Thrombosis.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis commonly with cardiac complications. We describe a case of anti-PR3 ANCA-positive EGPA complicated by congestive heart failure and intraventricular thrombosis. Interestingly, the thrombus was resolved rapidly with steroid and cyclophosphamide in the setting of interrupted anticoagulation. To the best of our knowledge, we report the first case of anti-PR3 positive EGPA with extensive cardiac involvement. Our patient had overlapping features with previously studied ANCA-positive and ANCA-negative EGPA cases. We also hypothesize that the thrombogenic potential of eosinophils may play a central role in thrombogenesis in EGPA and aggressive immunosuppressive therapy remains the cornerstone of treatment, and the addition of anticoagulation therapy in the setting of thrombus formation and also very high risk of bleeding needs to be considered cautiously.