Stem Cell Therapy for Corneal Regeneration Medicine and Contemporary Nanomedicine for Corneal Disorders.
The ocular surface is the outermost part of the visual system that faces many extrinsic or intrinsic threats, such as chemical burn, infectious pathogens, thermal injury, Stevens-Johnson syndrome, ocular pemphegoid, and other autoimmune diseases. The cornea plays an important role in conducting light into the eyes and protecting intraocular structures. Several ocular surface diseases will lead to the neovascularization or conjunctivalization of corneal epithelium, leaving opacified optical media. It is believed that some corneal limbal cells may present stem cell-like properties and are capable of regenerating corneal epithelium. Therefore, cultivation of limbal cells and reconstruction of the ocular surface with these limbal cell grafts have attracted tremendous interest in the past few years. Currently, stem cells are found to potentiate regenerative medicine by their capability of differentiation into multiple lineage cells. Among these, the most common cell sources for clinical use are embryonic, adult, and induced stem cells. Different stem cells have varied specific advantages and limitations for in vivo and in vitro expansion. Other than ocular surface diseases, culture and transplantation of corneal endothelial cells is another major issue for corneal decompensation and awaits further studies to find out comprehensive solutions dealing with nonregenerative corneal endothelium. Recently, studies of in vitro endothelium culture and ρ-associated kinase (ROCK) inhibitor have gained encouraging results. Some clinical trials have already been finished and achieved remarkable vision recovery. Finally, nanotechnology has shown great improvement in ocular drug delivery systems during the past two decades. Strategies to reconstruct the ocular surface could combine with nanoparticles to facilitate wound healing, drug delivery, and even neovascularization inhibition. In this review article, we summarized the major advances of corneal limbal stem cells, limbal stem cell deficiency, corneal endothelial cell culture/transplantation, and application of nanotechnology on ocular surface reconstruction. We also illustrated potential applications of current knowledge for the future treatment of ocular surface diseases.


Short-time dynamics and critical behavior of the three-dimensional site-diluted Ising model.
Monte Carlo simulations of the short-time dynamic behavior are reported for three-dimensional weakly site-diluted Ising model with spin concentrations p=0.95 and 0.8 at criticality. In contrast to studies of the critical behavior of the pure systems by the short-time dynamics method, our investigations of site-diluted Ising model have revealed three stages of the dynamic evolution characterizing a crossover phenomenon from the critical behavior typical for the pure systems to behavior determined by the influence of disorder. The static and dynamic critical exponents are determined with the use of the corrections to scaling for systems starting separately from ordered and disordered initial states. The obtained values of the exponents demonstrate a universal behavior of weakly site-diluted Ising model in the critical region. The values of the exponents are compared to results of numerical simulations which have been obtained in various works and, also, with results of the renormalization-group description of this model.


RNA search engines empower the bacterial intranet.
RNA acts not only as an information bearer in the biogenesis of proteins from genes, but also as a regulator that participates in the control of gene expression. In bacteria, small RNA molecules (sRNAs) play controlling roles in numerous processes and help to orchestrate complex regulatory networks. Such processes include cell growth and development, response to stress and metabolic change, transcription termination, cell-to-cell communication, and the launching of programmes for host invasion. All these processes require recognition of target messenger RNAs by the sRNAs. This review summarizes recent results that have provided insights into how bacterial sRNAs are recruited into effector ribonucleoprotein complexes that can seek out and act upon target transcripts. The results hint at how sRNAs and their protein partners act as pattern-matching search engines that efficaciously regulate gene expression, by performing with specificity and speed while avoiding off-target effects. The requirements for efficient searches of RNA patterns appear to be common to all domains of life.


C-X-C Motif Chemokine 3 Promotes the Inflammatory Response of Microglia after Escherichia coli-Induced Meningitis.
Meningitis is a major clinical manifestation of Escherichia coli (E. coli) infection characterized by inflammation of the meninges and subarachnoid space. Many chemokines are secreted during meningitic E. coli infection, of which C-X-C motif chemokine 3 (CXCL3) is the most highly expressed. However, it is unclear how CXCL3 plays a role in meningitic E. coli infection. Therefore, this study used in vitro and in vivo assays to clarify these contributions and to identify novel therapeutic targets for central nervous system inflammation. We found a significantly upregulated expression of CXCL3 in human brain microvascular endothelial cells and U251 cells after meningitic E. coli infection, and the CXCL3 receptor, C-X-C motif chemokine receptor 2 (CXCR2), was expressed in microglia. Furthermore, CXCL3 induced M1 microglia by selectively activating mitogen-activated protein kinases signaling and significantly upregulating tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide synthase 2 (NOS2), and cluster of differentiation 86 (CD86) expression levels, promoting an inflammatory response. Our findings clarify the role of CXCL3 in meningitic E. coli-induced neuroinflammation and demonstrate that CXCL3 may be a potential therapeutic target for future investigation and prevention of E. coli-induced neuroinflammation.


Obesity related measurements and joint space width in patients with knee osteoarthritis.
The aim of this study is to analyze the relationship between body mass index and obesity related measurements and tibiofemoral joint space which have been the principal method of radiographic evaluation in progression and therapeutic trials of knee osteoarthritis. Fifty-five female patients with the diagnosis of osteoarthritis in knees according to the criteria of American College of Rheumatology in knees were included in the study. The mean age of patients was 57,42+/-8,60(SD) years with a range of 42-77. Medial and lateral compartment joint space widths were measured on antero-posterior knee radiography. Body mass index, triceps, biceps, subscapular and suprailiac skinfold thickness, waist and hip circumference were measured. Body composition was determined by dual energy X-ray absorpsiometry (DEXA) (Norland XR 46) and total lean mass (g), total fat mass (g), trunk lean mass, trunk fat mass, abdomen lean mass, abdomen fat mass measurements were recorded. Patients with body mass index>30 were accepted as obese patients. According to these criteria 33 of the 55 patients were obese. Tibial medial compartment and tibial lateral compartment measurements of obese patients were significantly lower than nonobese patients (p=0,000, p=0,003 respectively). Body mass index was correlated with total lean mass, total fat mass, trunk fat mass, abdominal fat mass, leg fat mass. Tibial medial compartment and tibial lateral compartment space measurements were negatively correlated with body mass index. Our results revealed significant difference in both medial and lateral joint spaces of obese and nonobese patients with knee osteoarthritis. Medial and lateral joint spaces of obese patients were narrower than nonobese osteoarthritis patients. The more body mass index had the patients the narrower joint space they had displayed. However body composition analysis and obesity related measurements did not show additional correlation with tibial compartment measurement.


Brain tumors studied by computerized tomography.
A brief description of the method and clinical application of CT is given. Various features and absorption values of different intracranial neoplasms are described and compared. The effects of CT on other special diagnostic procedures are discussed. It is emphasized that contrast medium enhancement significantly increases the sensitivity and specificity of the technique when applied to patients who have or are suspected of having cerebral neoplasms.


The effect of hydrogen sulfide-releasing naproxen (ATB-346) versus naproxen on formation of stress-induced gastric lesions, the regulation of systemic inflammation, hypoxia and alterations in gastric microcirculation.
Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin or naproxen is limited due to the gastrotoxicity evoked by these compounds. Endogenous hydrogen sulfide (H2s) and delivered via an H2s donor have been shown to play important role in the maintenance of gastric mucosal integrity. This study aimed to compare the effects of naproxen and an H2s-releasing naproxen derivative (ATB-346) on gastric lesion induction by water immersion and restraint stress (WRS), the alterations in gastric blood flow (GBF) and the influence of these drugs on systemic inflammation. Wistar rats were pretreated i.g. with vehicle, naproxen (20 mg/kg) or ATB-346 (equimolar dose) or NaHS (5 mg/kg), the H2s donor, combined with naproxen and exposed to 3.5 hours of WRS. The gastric lesion number and GBF were assessed by planimetry and laser Doppler flowmetry, respectively. Plasma concentrations of interleukins: IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and GM-CSF were determined by Luminex system and gastric mucosal protein expression of cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), hypoxia inducible factor-1α (HIF-1α), heme oxygenase-1 (HO-1) and cyclooxygenase (COX-2) were analyzed by Western blot. Pretreatment with naproxen increased the number of WRS stress-induced gastric lesions and significantly decreased GBF as compared with vehicle (p < 0.05). In contrast, pretreatment with ATB-346 or naproxen combined with NaHS significantly reduced WRS-lesions number and elevated GBF as compared with naproxen (p < 0.05). Naproxen significantly increased gastric mucosal protein expression of CSE, Nrf-2 and HIF-1α as compared with vehicle (p < 0.05), but failed to affect CBS, 3-MST and HO-1. ATB-346 significantly increased Nrf-2 and HO-1 protein expression as compared with vehicle (P < 0.05) but did not affect the protein expression of CSE, CBS, 3-MST or HIF-1α. ATB-346 but not naproxen decreased COX-2 protein expression in gastric mucosa compromised by WRS (p < 0.05). Exposure to WRS increased plasma concentration of all investigated cytokines (p < 0.05). ATB-346 but not naproxen decreased plasma content of IL-1α, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α and IFN-γ in rats exposed to WRS (p < 0.05). We conclude that H2s through its vasoactive properties attenuates the gastrotoxic effects of naproxen, which increased stress-induced hypoxia in gastric mucosa. In contrast to naproxen, ATB-346 decreased stress-induced systemic inflammation and pro-inflammatory COX-2 expression in the gastric mucosa. The decreased gastrotoxicity of ATB-346 could be due to upregulation of Nrf-2/HO-1 pathway mediated by the release of H2s.


Biocidal activity of a light-absorbing fluorescent conjugated polyelectrolyte.
Herein we describe studies that indicate a cationic conjugated polyelectrolyte shows biocidal activity against gram-negative bacteria (Escherichia coli, E. coli, BL21, with plasmids for Azurin and ampicillin resistance) and gram-positive bacterial spores (Bacillus anthracis, Sterne, B. anthracis, Sterne). These studies were carried out with aqueous suspensions of the conjugated polyelectrolyte, with the polyelectrolyte in supported formats and with samples in which the conjugated polyelectrolyte was coated on the bacteria. The results are interesting in that the biocidal activity is light-induced and appears effective due to the ability of the conjugated polyelectrolyte to form a surface coating on both types of bacteria. The effects observed here should be general and suggest that a range of conjugated polyelectrolytes in different formulations may provide a useful new class of biocides for both dark and light-activated applications.


The effect of alpha 2HS glycoprotein on lymphocyte reactivity to phytohemagglutinin.
The effect of alpha 2HS glycoprotein on lymphocyte reactivity to phytohemagglutinin (PHA) was investigated. The results show that alpha 2HS glycoprotein, rather than enhancing lymphocyte reactivity to PHA as suggested by earlier correlation studies, inhibits such reactivity. Experiments suggest that this inhibition is unlikely to be the result of alpha 2HS glycoprotein binding either PHA or 3H-thymidine but is more likely to act at the cellular level.


Accuracy of the ultrasound attenuation coefficient for the evaluation of hepatic steatosis: a systematic review and meta-analysis of prospective studies.
The accurate detection and quantification of hepatic steatosis using a noninvasive method are important for the management of nonalcoholic fatty liver disease. We performed a systematic review and meta-analysis of the accuracy of the ultrasound-measured attenuation coefficient (AC) in the evaluation of hepatic steatosis. The PubMed, Embase, and Cochrane databases were searched for prospective studies reporting the diagnostic accuracy of AC for assessing hepatic steatosis. The meta-analytic pooled sensitivity and specificity of AC for any grade of steatosis (S≥1) and advanced steatosis (S≥2) were estimated using a bivariate random-effects model. Meta-regression analysis was conducted to investigate the causes of heterogeneity among studies. Thirteen studies including 1,509 patients were identified. The pooled sensitivity and specificity of AC for S≥1 were 76% (95% confidence interval [CI], 73% to 80%; I2=43%) and 84% (95% CI, 77% to 89%; I2=74%), respectively, while for S≥2 they were 87% (95% CI, 83% to 91%; I2=0%) and 79% (95% CI, 75% to 83%; I2=59%), respectively. Study heterogeneity was associated with body mass index (BMI) and the prevalence of steatosis or significant fibrosis. AC can be clinically useful for assessing hepatic steatosis, with good overall diagnostic performance. The data reported in the published literature differed according to BMI and the prevalence of steatosis or significant fibrosis, and careful interpretation with consideration of these factors might be needed.


Trans fatty acids in human milk in Canada declined with the introduction of trans fat food labeling.
Trans fatty acids in human milk have raised concerns because of possible adverse effects on infant growth and development. Analyses of human milk in the late 1990s in Canada showed high amounts of trans fatty acids from partially hydrogenated oils. Canada introduced labeling of trans fatty acids on retail foods in 2003. We analyzed trans and cis unsaturated and saturated fatty acids in human milk collected from 87 women in 2004-2006 and compared the levels to those in milk collected from 103 women in 1998 and analyzed using similar methods. The total trans fatty acids (mean +/- SEM, g/100 g fatty acids) in human milk in Canada decreased significantly, from 7.1 +/- 0.32 in 1998 to 6.2 +/- 0.48, 5.3 +/- 0.49, and 4.6 +/- 0.32 over 3 consecutive 5-mo periods from November 2004 to January 2006. The milk total trans fatty acids were significantly and inversely related to 16:0, 18:2(n-6), 18:3(n-3), 20:4(n-6), 22:4(n-6), and 22:5(n-6) and positively related to 18:0 and conjugated linolenic acids (P < 0.05, n = 190). The estimated exposures of exclusively breast-fed infants to trans fatty acids decreased from a mean and 95th percentile intake of 2.0 and 4.4 g x infant(-1) x d(-1) in 1998 to 1.33 and 2.41 g x infant(-1) x d(-1), respectively, in late 2005. The estimated intake of the mothers was 4.0 (range 0.51-12.3) and 2.2 (0.56-7.65) g x person(-1) x d(-1) in 1998 and late 2005, respectively. Our studies show trans fatty acids have decreased in human milk in Canada, which suggests a concomitant decrease in trans fatty acid intake among lactating women and breast-fed infants.


Voltage-induced bending and electromechanical coupling in lipid bilayers.
The electrical properties of the cellular membrane are important for ion transport across cells and electrophysiology. Plasma membranes also resist bending and stretching, and mechanical properties of the membrane influence cell shape and forces in membrane tethers pulled from cells. There exists a coupling between the electrical and mechanical properties of the membrane. Previous work has shown that applied voltages can induce forces and movements in the lipid bilayer. We present a theory that computes membrane bending deformations and forces as the applied voltage is changed. We discover that electromechanical coupling in lipid bilayers depends on the voltage-dependent adsorption of ions into the region occupied by the phospholipid head groups. A simple model of counter-ion absorption is investigated. We show that electromechanical coupling can be measured using membrane tethers and we use our model to predict the membrane tether tension as a function of applied voltage. We also discuss how electromechanical coupling in membranes may influence transmembrane protein function.


Isolation and characterization of beta 1-adrenergic receptors from adult, rat cardiac myocytes.
The beta-receptors were isolated from rat cardiac myocytes and characterized. Isolated myocytes were prepared from adult rat hearts and characterized for viability. Membrane proteins were solubilized from myocytes with 1% Triton X-102. The solubilized membrane proteins were fractionated by DEAE-Sephacel ion exchange column chromatography. Two major protein peaks were obtained. The second protein peak sample was found to contain beta-receptors to which 125I-15-(4'-azido-3'-iodobenzyl)-carazolol (125I-ABC) was specifically bound. This sample was labeled covalently with 125I-ABC by UV irradiation. The radiolabeled sample was applied to a Sepharose CL-6B gel column. Two radiolabeled protein peaks, one with a molecular weight of approximately 570,000 and the other with a molecular weight of approximately 95,000 were found. When the 570,000-dalton complex was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions, it was dissociated into a component with a molecular weight of 66,000. The 95,000-dalton complex was dissociated into a 58,000-dalton component upon SDS-PAGE under reducing conditions. An excess amount of isoproterenol and propranolol decreased photolabeling of the beta-receptors with 125I-ABC by 60% and 40%, respectively.


Apathy and Type 2 Diabetes among American Indians: Exploring the Protective Effects of Traditional Cultural Involvement.
In this study we examine relationships between traditional cultural factors, apathy, and health-related outcomes among a sample of American Indian adults with type 2 diabetes. Participants completed cross-sectional interviewer-assisted paper and pencil surveys. We tested a proposed model using latent variable path analysis in order to understand the relationships between cultural participation, apathy, frequency of high blood sugar symptoms, and health-related quality of life. The model revealed significant direct effects from cultural participation to apathy, and apathy to both health-related outcomes. No direct effect of cultural participation on either health-related outcome was found; however, cultural participation had a negative indirect effect through apathy on high blood sugar and positive indirect effects on health-related quality of life. This study highlights a potential pathway of cultural involvement to positive diabetes outcomes.


Improvement of human lymphocyte proliferation and alteration of IL-2 secretion kinetics by alpha-thioglycerol.
Using a novel flow cytometric assay (BrdU/Hoechst flow cytometry) for the visualization and quantitation of cell activation and cell progression through multiple cell cycles we show that (1) resting mononuclear cells from human venous blood respond to polyclonal activation in a highly asynchronous fashion, as some of these cells enter their first cell cycle as early as 30 and as late as 80 hrs after exposure to the mitogen; (2) reducing agents improve the mitogenic response of polyclonally activated human lymphocytes by increasing the recruitment of non-cycling G0/G1 cells; (3) of 8 reducing agents tested, alpha-thioglycerol proved most effective with respect to enhancing recruitment into the cell cycle; (4) the effective agents needs to be present permanently for maximum response; (5) the growth-promoting effect of alpha-thioglycerol is mediated, but not solely caused by increased IL2 production. The latter conclusion was arrived at by using the IL2-dependent CTLL cell line in conjunction with the BrdU/Hoechst flow technique as a sensitive bioassay system for the growth promoting activity of the cell cycle progression factor IL2; (6) exogenously added IL-2, however, did not improve cell activation towards proliferation. These data indicate that increased IL-2 levels are probably due to increased cell activation rates but are not the primary cause of improvement of human lymphocyte proliferation.


Important health provider characteristics: the perspective of urban ninth graders.
Clinicians caring for adolescents may be better positioned to provide health care when equipped with an understanding of adolescents' preferences regarding provider characteristics. The purpose of this study is to obtain a manageable framework of adolescents' concerns about health care providers. A series of qualitative and quantitative data-collection methods were used to elicit and organize ideas about health care providers from ninth-grade students in Philadelphia. A 5-point Likert survey, based on ideas generated and prioritized in earlier qualitative stages, was administered in school. Exploratory and confirmatory factor analysis was used to uncover latent factors. A total of 2602 students returned usable surveys. A confirmatory factor analysis model including four latent factors (patient's interpersonal relationship with provider, concern for physical safety, concern for emotional safety, and provider counseling ability) explained 51.6% of the model variability. Urban ninth graders want providers with whom they can develop strong relationships, feel emotionally and physically safe, and turn to for counseling. Communication with adolescent-aged patients should be a standard component of health care training and should promote provider sensitivity to adolescent fears and needs in the health care setting.


Scutellarin Inhibits Glioblastoma Growth in a Dose-dependent Manner by Suppressing the p63 Signaling Pathway.
Although scutellarin has been extensively investigated, its effects on glioma are unclear. This study intended to reveal this regulation and the underlying mechanisms. The U251, M059K, and SF-295 cell lines were treated with gradient concentrations of scutellarin and then IC50 was calculated. SF-295 cells selected for subsequent procedures were treated with four concentrations of scutellarin. Then, proliferation, apoptosis, and cell cycle, as well as the protein and mRNA expression of significantly differentially expressed genes identified by next-generation sequencing (NGS), were examined. The curative effect of scutellarin was validated by 5-FU as the positive control. Scutellarin inhibited proliferation and induced apoptosis and G2/M cell cycle arrest in the SF-295 cell line in a dose-dependent manner. The effect of scutellarin was similar to but significantly weaker than the effect of 5-FU. The NGS results showed that genes associated with anti-apoptosis signaling pathways were significantly reduced after treatment. The Western blotting results indicated that the expressions of TP63/BIRC3/TRAF1/Bcl-2 were reduced in a dose-dependent manner, as well as the mRNA levels determined by qRT‒PCR. Our original conclusion revealed that scutellarin may inhibit glioma growth in a dose-dependent manner via the p63 signaling pathway which may provide a potential medicine for glioma chemotherapy.


Do school surroundings matter? Alcohol outlet density, perception of adolescent drinking in public, and adolescent alcohol use.
The aim of the present study was to investigate the relationship between alcohol outlet density, perception of adolescent drinking in public (both assessed at the school level), and adolescent drinking and drunkenness at individual level. Hierarchical linear regression models were calculated based on data from 1194 ninth graders in Switzerland (mean age=15.3, S.D.=0.7) and their schoolmasters (n=61). Apart from the positive main effects, the results reveal a negative interaction of alcohol outlet density and perception of adolescent drinking in public in predicting individual alcohol use among adolescents. In regions with a high density of shops, it appears that the schoolmasters' perception reflects the general drinking norm of the area where the school is located rather than the actual drinking level of adolescents. More research is needed, particularly in Europe and among adolescent populations, to reach a better understanding of school level predictors of adolescent alcohol use.


Molecular and electron microscopic identification of Wolbachia in Culex pipiens complex populations from the Upper Rhine Valley, Germany, and Cebu City, Philippines.
We detected Wolbachia infections in Culex pipiens complex mosquitoes from the Upper Rhine Valley, Germany, and Cebu City, Philippines, with the use of polymerase chain reaction (PCR) amplification of the 16S rDNA of the bacteria and further confirmation by electron microscopy. Species of 5 different autogenous and anautogenous populations of Culex pipiens from Germany and 1 population of Culex quinquefasciatus from the Philippines were used in this study. Larvae were sampled from different localities and reared to the adult stage for further processing. Whole adult males and the heads of adult females were processed by PCR, whereas the abdomens of females were used for electron microscopic study when an infection was detected by PCR. All Culex populations assayed by PCR showed infection of Wolbachia at rates between 10 and 100%. Females from different populations exhibited higher infection rates than did the males, and, likewise, Cx. pipiens populations that were autogenous showed higher infection rates of Wolbachia than did anautogenous individuals. In Cx. quinquefasciatus populations, males were infected at 33.33% and females, only 10%. We studied the ultrastructure of Wolbachia in the ovaries of species belonging to Cx. pipiens complex by means of transmission electron microscopy. The bacteria exhibited typical morphology for Wolbachia with 3 enveloping membranes.


T cell epitope mapping of the e-protein of West Nile virus in BALB/c mice.
West Nile virus (WNV) is a zoonotic virus, which is transmitted by mosquitoes. It is the causative agent of the disease syndrome called West Nile fever. In some human cases, a WNV infection can be associated with severe neurological symptoms. The immune response to WNV is multifactorial and includes both humoral and cellular immunity. T-cell epitope mapping of the WNV envelope (E) protein has been performed in C57BL/6 mice, but not in BALB/c mice. Therefore, we performed in BALB/c mice a T-cell epitope mapping using a series of peptides spanning the WNV envelope (E) protein. To this end, the WNV-E specific T cell repertoire was first expanded by vaccinating BALB/c mice with a DNA vaccine that generates subviral particles that resemble West Nile virus. Furthermore, the WNV structural protein was expressed in Escherichia coli as a series of overlapping 20-mer peptides fused to a carrier-protein. Cytokine-based ELISPOT assays using these purified peptides revealed positive WNV-specific T cell responses to peptides within the different domains of the E-protein.


Rational synthesis of Ni nanoparticle-embedded porous graphitic carbon nanosheets with enhanced lithium storage properties.
Carbon-based materials have recently received increased attention as very promising anode materials for rechargeable lithium-ion batteries (LIBs) because of their non-toxicity, low cost, and excellent performances. Nanostructure engineering has been demonstrated as an effective approach to improve the electrochemical performance of electrode materials. Here, we present a facile and scalable synthesis of two-dimensional (2D) porous graphitic carbon nanosheets embedded by numerous homogeneously dispersed Ni nanoparticles. With both structural and compositional advantages, the as-synthesized nanohybrid manifests a very stable high reversible capacity of 740 mA h g(-1) after 100 cycles at a current density of 100 mA g(-1), and also excellent rate capability and cycling stability. We believe that the synthetic strategy outlined here can be extended to other rationally designed anode materials with high performances in LIBs.


In Situ Analysis of Gas Generation in Lithium-Ion Batteries with Different Carbonate-Based Electrolytes.
Gas generation in lithium-ion batteries is one of the critical issues limiting their safety performance and lifetime. In this work, a set of 900 mAh pouch cells were applied to systematically compare the composition of gases generated from a serial of carbonate-based composite electrolytes, using a self-designed gas analyzing system. Among electrolytes used in this work, the composite γ-butyrolactone/ethyl methyl carbonate (GBL/EMC) exhibited remarkably less gassing because of the electrochemical stability of the GBL, which makes it a promising electrolyte for battery with advanced safety and lifetime.


Reversal of stress- and CRF-induced anorexia in rats by the synthetic nociceptin/orphanin FQ receptor agonist, Ro 64-6198.
(1S,3aS)-8-(2,3,3,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (Ro 64-6198), a non-peptidic agonist for the opioid receptor-like1 (ORL1) receptor, exhibits anxiolytic properties in stressful conditions. The present study was aimed at evaluating whether activation of ORL1 receptors by Ro 64-6198 may reverse the anorectic effect of restraint stress or intracerebroventricular (ICV) CRF injection. In body restraint experiments, 20-h food deprived rats were treated with intraperitoneal (IP) injection of Ro 64-6198 or vehicle. Ten minutes later, they were confined in cylindrical Plexiglas tubes for 60 min and then returned to their cage with food. In CRF experiments, 20-h food deprived rats were IP injected with Ro 64-6198 or vehicle. Ten minutes later, they received ICV CRF, 200 ng/rat or vehicle; food was offered after 20 min. Intraperitoneal (IP) pretreatment with Ro 64-6198 reversed the hypophagic effect induced by both restraint or CRF; the effect was statistically significant at the three doses tested (0.3, 1.0 or 2.5 mg/kg). ICV administration of the selective ORL1 receptor antagonist [Nphe(1)]NC(1-13)NH(2)(two injections of 33 or 66 microg/rat) abolished the effect of Ro 64-6198 on CRF-induced anorexia. In freely feeding rats, Ro 64-6198 significantly increased feeding at 2.5, but not at 0.3 or 1.0 mg/kg; in food deprived rats, Ro 64-6198 (0.3 or 1.0 mg/kg) did not modify food intake. Thus, reversal of stress- and CRF-induced anorexia by Ro 64-6198 can be evoked at doses lower than those that are hyperphagic. Ro 64-6198 (1 or 2.5 mg/kg) did not modify the anorectic effect of E. coli lipopolysaccharide, suggesting that its effect is selective for stress- or CRF-induced anorexia. Lastly, the benzodiazepine diazepam was unable to reduce the anorectic effect of CRF at the anxiolytic dose of 0.3 mg/kg, and partially reduced it at the hyperphagic dose of 1 mg/kg. The results of this study show that the non-peptidic ORL1 receptor agonist Ro 64-6198 markedly and selectively inhibits the anorectic effect of stress and CRF, and provide evidence that this effect is mediated by ORL1 receptors. Thus, Ro 64-6198 may represent an interesting tool for treatment of stress-induced anorexia.


Spatiotemporal features of neurogenesis in the retina of medaka, Oryzias latipes.
The vertebrate retina is very well conserved in evolution. Its structure and functional features are very similar in phyla as different as primates and teleost fish. Here, we describe the spatiotemporal characteristics of neurogenesis in the retina of a teleost, medaka, and compare them with other species, primarily the zebrafish. Several intriguing differences are observed between medaka and zebrafish. For example, photoreceptor differentiation in the medaka retina starts independently in two different areas, and at more advanced stages of differentiation, medaka and zebrafish retinae display obviously different patterns of the photoreceptor cell mosaic. Medaka and zebrafish evolutionary lineages are thought to have separated from each other 110 million years ago, and so the differences between these species are not unexpected, and may be exploited to gain insight into the architecture of developmental pathways. Importantly, this work highlights the benefits of using multiple teleost models in parallel to understand a developmental process.


Progress on the functional role of oleosin gene family in plants.
Oil bodies, also known as lipid droplets or oil droplets, are important organelles for oil storage in plant cells. The oil body is composed of a monolayer of phospholipid membrane encapsulating neutral fatty acids, and a variety of membrane proteins are embedded in the membrane, including oleosin, caleosin and steroleosin, of which oleosin accounts for 80%-90%. Oleosin plays important biological roles in various biological roles, such as affecting the size and stability of oil bodies, formation and degradation of oil bodies, lipid metabolism, and seed maturation and germination. In this review, we summarize the sequence and structural characteristics of oleosin and its important role in plant growth and development based on the research progress of plant oleosin gene families at home and abroad in recent years. Additionally, we discuss the application of oleosin in actual production and problems in the research and application, in order to provide a useful reference for people to further study the functions of oleosin-related molecules and their application in production practice.


Characteristics of Whale Müller Glia in Primary and Immortalized Cultures.
Müller cells are the principal glial cells in the retina and they assume many of the functions carried out by astrocytes, oligodendrocytes and ependymal cells in other regions of the central nervous system. Müller cells express growth factors, neurotransmitter transporters and antioxidant agents that could fulfill important roles in preventing excitotoxic damage to retinal neurons. Vertebrate Müller cells are well-defined cells, characterized by a common set of features throughout the phylum. Nevertheless, several major differences have been observed among the Müller cells in distinct vertebrates, such as neurogenesis, the capacity to reprogram fish Müller glia to neurons. Here, the Müller glia of the largest adult mammal in the world, the whale, have been analyzed, and given the difficulties in obtaining cetacean cells for study, these whale glia were analyzed both in primary cultures and as immortalized whale Müller cells. After isolating the retina from the eye of a beached sei whale (Balaenoptera borealis), primary Müller cell cultures were established and once the cultures reached confluence, half of the cultures were immortalized with the simian virus 40 (SV40) large T-antigen commonly used to immortalize human cell lines. The primary cell cultures were grown until cells reached senescence. Expression of the principal molecular markers of Müller cells (GFAP, Vimentin and Glutamine synthetase) was studied in both primary and immortalized cells at each culture passage. Proliferation kinetics of the cells were analyzed by time-lapse microscopy: the time between divisions, the time that cells take to divide, and the proportion of dividing cells in the same field. The karyotypes of the primary and immortalized whale Müller cells were also characterized. Our results shown that W21M proliferate more rapidly and they have a stable karyotype. W21M cells display a heterogeneous cell morphology, less motility and a distinctive expression of some typical molecular markers of Müller cells, with an increase in dedifferentiation markers like α-SMA and β-III tubulin, while they preserve their GS expression depending on the culture passage. Here we also discuss the possible influence of the animal's age and size on these cells, and on their senescence.


Multiple expression of Ig lambda-chain encoding RNA species in murine plasmacytoma cells.
The murine plasmacytoma MOPC 315, which synthesizes a complete IgA molecule containing lambda 2 light chains, is shown to synthesize a polypeptide related to the lambda 1 light chain. The abnormal lambda 1 polypeptide (m.w. approximately equal to 18,000) is encoded by a shorter polyA+ mRNA than the lambda 1 mRNAs of lambda 1-producing plasmacytomas. Polypeptides containing lambda 1-specific antigenic determinants have been found to be synthesized both in vitro by translations of RNA and in intact cells. HOPC-1, a lambda 1-producing plasmacytoma, was found to synthesize, in addition to the normal lambda 1-encoding mRNA, a lambda 2 RNA of normal length. A lambda 2-producing hybridoma does not appear to synthesize RNA encoding lambda 1 sequences. The results presented here show that more than 1 light chain gene may be transcribed within a single plasmacytoma cell. Although more than 1 light chain gene may be transcribed, the product of only 1 gene appears to be utilized for the synthesis of complete immunoglobulin molecules. This suggests novel mechanisms for the control of immunoglobulin expression.


Effect of curcumin in mice model of vincristine-induced neuropathy.
Curcumin exhibits a wide spectrum of biological activities which include neuroprotective, antinociceptive, anti-inflammatory, and antioxidant activity. The present study evaluates the effect of curcumin in vincristine-induced neuropathy in a mice model. Vincristine sulfate (0.1 mg/kg, i.p. for 10 consecutive days) was administered to mice to induce neuropathy. Pain behavior was assessed at different days, i.e., 0, 7, 10, and 14 d. Sciatic nerve total calcium, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), nitric oxide (NO), and lipid peroxidation (LPO) were also estimated after the 14th day of study. Pregabalin (10 mg/kg, p.o.) and curcumin (15, 30, and 60 mg/kg, p.o.) were administered for 14 consecutive days. Curcumin at 60 mg/kg significantly attenuated the vincristine-induced neuropathic pain manifestations in terms of thermal hyperalgesia (p < 0.001) and allodynia (p < 0.001); mechanical hyperalgesia (p < 0.001); functional loss (p < 0.001); and in the delayed phase of formalin test (p < 0.001). Curcumin at 30 and 60 mg/kg exhibited significant changes (p < 0.001) in antioxidant levels and in total calcium levels in vincristine-injected mice. Curcumin at 30 and 60 mg/kg dose levels significantly attenuated vincristine-induced neuropathy which may be due to its multiple actions including antinociceptive, calcium inhibitory, and antioxidant effect.


Equivalent peak resolution: characterization of the extent of separation for two components based on their relative peak overlap.
Although the classical formula of peak resolution was derived to characterize the extent of separation only for Gaussian peaks of equal areas, it is often used even when the peaks follow non-Gaussian distributions and/or have unequal areas. This practice can result in misleading information about the extent of separation in terms of the severity of peak overlap. We propose here the use of the equivalent peak resolution value, a term based on relative peak overlap, to characterize the extent of separation that had been achieved. The definition of equivalent peak resolution is not constrained either by the form(s) of the concentration distribution function(s) of the peaks (Gaussian or non-Gaussian) or the relative area of the peaks. The equivalent peak resolution value and the classically defined peak resolution value are numerically identical when the separated peaks are Gaussian and have identical areas and SDs. Using our new freeware program, Resolution Analyzer, one can calculate both the classically defined and the equivalent peak resolution values. With the help of this tool, we demonstrate here that the classical peak resolution values mischaracterize the extent of peak overlap even when the peaks are Gaussian but have different areas. We show that under ideal conditions of the separation process, the relative peak overlap value is easily accessible by fitting the overall peak profile as the sum of two Gaussian functions. The applicability of the new approach is demonstrated on real separations.


Eosinophilic fasciitis in a pediatric patient.
We report the case of a pediatric patient with eosinophilic fasciitis, who was successfully treated with early high dose corticosteroids and subsequent use of mycophenolate mofetil. We believe that the early institution of corticosteroids helped to suppress the early inflammatory part of the disease and the subsequent use of mycophenolate mofetil maintained this and may have also helped prevent fibrotic skin changes.


Enantioselective Synthesis of the Tricyclic Core of FR901483 Featuring a Rh-Catalyzed [2+2+2] Cycloaddition.
An efficient approach to the tricyclic framework of FR901483 is described. The sequence features a [3, 3]-sigmatropic rearrangement of a cyanate into an isocyanate, followed by its subsequent asymmetric rhodium-catalyzed [2+2+2] cycloaddition with a terminal alkyne for the synthesis of the indolizidine core. The aza-tricyclic core is completed using an intramolecular benzoin reaction to close the last ring of the natural product. Through a model study of the key cycloaddition, we evaluated the impact of different substituents on the tether of the alkenyl isocyanate.


Screening of DNA Damage Repair Genes Involved in the Prognosis of Triple-Negative Breast Cancer Patients Based on Bioinformatics.
Background: Triple-negative breast cancer (TNBC) is a special subtype of breast cancer with poor prognosis. DNA damage response (DDR) is one of the hallmarks of this cancer. However, the association of DDR genes with the prognosis of TNBC is still unclear. Methods: We identified differentially expressed genes (DEGs) between normal and TNBC samples from The Cancer Genome Atlas (TCGA). DDR genes were obtained from the Molecular Signatures Database through six DDR gene sets. After the expression of six differential genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR), we then overlapped the DEGs with DDR genes. Based on univariate and LASSO Cox regression analyses, a prognostic model was constructed to predict overall survival (OS). Kaplan-Meier analysis and receiver operating characteristic curve were used to assess the performance of the prognostic model. Cox regression analysis was applied to identify independent prognostic factors in TNBC. The Human Protein Atlas was used to study the immunohistochemical data of six DEGs. The prognostic model was validated using an independent dataset. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were performed by using gene set enrichment analysis (GSEA). Single-sample gene set enrichment analysis was employed to estimate immune cells related to this prognostic model. Finally, we constructed a transcriptional factor (TF) network and a competing endogenous RNA regulatory network. Results: Twenty-three differentially expressed DDR genes were detected between TNBC and normal samples. The six-gene prognostic model we developed was shown to be related to OS in TNBC using univariate and LASSO Cox regression analyses. All the six DEGs were identified as significantly up-regulated in the tumor samples compared to the normal samples in qRT-PCR. The GSEA analysis indicated that the genes in the high-risk group were mainly correlated with leukocyte migration, cytokine interaction, oxidative phosphorylation, autoimmune diseases, and coagulation cascade. The mutation data revealed the mutated genes were different. The gene-TF regulatory network showed that Replication Factor C subunit 4 occupied the dominant position. Conclusion: We identified six gene markers related to DDR, which can predict prognosis and serve as an independent biomarker for TNBC patients.


Key Frame Extraction in the Summary Space.
Key frame extraction is an efficient way to create the video summary which helps users obtain a quick comprehension of the video content. Generally, the key frames should be representative of the video content, meanwhile, diverse to reduce the redundancy. Based on the assumption that the video data are near a subspace of a high-dimensional space, a new approach, named as key frame extraction in the summary space, is proposed for key frame extraction in this paper. The proposed approach aims to find the representative frames of the video and filter out similar frames from the representative frame set. First of all, the video data are mapped to a high-dimensional space, named as summary space. Then, a new representation is learned for each frame by analyzing the intrinsic structure of the summary space. Specifically, the learned representation can reflect the representativeness of the frame, and is utilized to select representative frames. Next, the perceptual hash algorithm is employed to measure the similarity of representative frames. As a result, the key frame set is obtained after filtering out similar frames from the representative frame set. Finally, the video summary is constructed by assigning the key frames in temporal order. Additionally, the ground truth, created by filtering out similar frames from human-created summaries, is utilized to evaluate the quality of the video summary. Compared with several traditional approaches, the experimental results on 80 videos from two datasets indicate the superior performance of our approach.


Isomeric DNA ladder formation of a plasmid encoding tobramycin resistance from Escherichia coli.
During a 20-month survey of resistance to three aminoglycosides (gentamicin, tobramycin, and amikacin) in Escherichia coli at a university hospital, six tobramycin-, kanamycin-resistant isolates containing a 50 kilobase conjugative R-plasmid which encoded an aminoglycoside phosphotransferase (APH-(3')) were isolated. The APH-(3') conferred resistance to kanamycin (MIC = 100 mg/L) but not to tobramycin (MIC = 20 mg/L). In both the original isolates and transconjugants the six R-plasmids demonstrated an isomeric ladder in the range of 50-112 kb, which was enhanced by exposure of the bacterial cultures to tobramycin. pJFJ2522 is the prototype for this group of plasmids. Bacterial DNA gyrase reversed the isomeric DNA ladder in pJFJ25222 by increasing the supercoiling of the plasmid DNA. Regardless of the level of supercoiling, the plasmids produced indistinguishable restriction endonuclease fragment patterns. The clinical isolates containing these plasmids demonstrated different restriction fragment length polymorphism (RFLP) of their EcoRI digested genomic DNA using E. coli rRNA as a probe. Ladder formation was plasmid specific since other tobramycin R-plasmids did not form a ladder, but it was not host specific. pJFJ25222 formed a ladder in a recA- host and displayed the same restriction pattern in a recA- as in a recA+ environment. In conclusion, pJFJ2522 contains a new tobramycin resistance gene whose mechanism of resistance is not known and whose product probably influences the isomerization of the plasmid.


Aortopexy for the treatment of tracheo - broncho - malacia in children.
Aortopexy has been demonstrated to be an effective procedure for the treatment of tracheo(broncho)malacia in children. Several operative approaches have been proposed in the literature, including left anterior thoracotomy, right thoracotomy, full median sternotomy, or a thoracoscopic approach. In this video tutorial we present our technique for anterior aortopexy using a limited upper sternotomy.


Enhanced Cell Viability and Migration of Primary Bovine Annular Fibrosus Fibroblast-like Cells Induced by Microsecond Pulsed Electric Field Exposure.
This study is the first to report the enhancement of cell migration and proliferation induced by in vitro microsecond pulsed electric field (μsPEF) exposure of primary bovine annulus fibrosus (AF) fibroblast-like cells. AF primary cells isolated from fresh bovine intervertebral disks (IVDs) are exposed to 10 and 100 μsPEFs with different numbers of pulses and applied electric field strengths. The results indicate that 10 μs-duration pulses induce reversible electroporation, while 100 μs pulses induce irreversible electroporation of the cells. Additionally, μsPEF exposure increased AF cell proliferation up to 150% while increasing the average migration speed by 0.08 μm/min over 24 h. The findings suggest that the effects of PEF exposure on cells are multifactorial-depending on the duration, intensity, and number of pulses used in the stimulation. This highlights the importance of optimizing the μsPEF parameters for specific cell types and applications. For instance, if the goal is to induce cell death for cancer treatment, then high numbers of pulses can be used to maximize the lethal effects. On the other hand, if the goal is to enhance cell proliferation, a combination of the number of pulses and the applied electric field strength can be tuned to achieve the desired outcome. The information gleaned from this study can be applied in the future to in vitro cell culture expansion and tissue regeneration.


Adaptive integration method for Monte Carlo simulations.
We present an adaptive sampling method for computing free energies, radial distribution functions, and potentials of mean force. The method is characterized by simplicity and accuracy, with the added advantage that the data are obtained in terms of quasicontinuous functions. The method is illustrated and tested with simulations on a high density fluid, including a stringent consistency test involving an unusual thermodynamic cycle that highlights its advantages.


A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study.
Neuropathic pain is difficult to diagnose and difficult to treat with certainty. So the aim of the study was to evaluate comparative clinical efficacy of pregabaline with amitriptyline and gabapentin in neuropathic cancer pain. A total of 120 patients with cancer having severe neuropathic cancer pain were enrolled in the study after taking approval from Institutional Ethics Committee and divided in to 4 groups: group AT-amitriptyline, group GB-gabapentin, group PG-pregabalin, and group PL-placebo. Oral morphine was used for rescue analgesic for continued pain. Pain score (Visual Analogue scale) and secondary outcome measures such as intensity of lancinating, dysesthesia, and burning on numerical rating scale, Global satisfaction score (GSS), Eastern Co-operative Oncology Group scoring (ECOG), and adverse effects were assessed. At the end of study there was significant decrease in pain score in group PG as compared to the other groups; group AT (P = .003), group GB (P = .042), and group PL (P = .024). Percentage of patients with lancinating pain and dysesthesia were significantly less in group PG as compared to groups GB and PL. All the patients in group PL needed rescue morphine. After 4 visits, maximum improvement in ECOG scoring and GSS scoring was observed in group PG patients. Our results suggested that all antineuropathic drugs are effective in relieving cancer-related neuropathic pain. There was statistically and clinically significant morphine sparing effect of pregabaline in relieving neuropathic cancer pain and neuropathic symptoms as compared to other antineuropathic drugs.


Lacrimal myoepithelial carcinoma ex recurrent pleomorphic adenoma: A clinicopathological report and review of the literature.
Myoepithelial carcinoma is an uncommon malignant tumor of the lacrimal gland, composed of neoplastic myoepithelial cells with an infiltrative growth. The present study describes a unique case of progressive proptosis and blindness of the right eye in a 68-year-old woman following total tumor removal for lacrimal pleomorphic adenoma. Clinical study, surgical exploration, and pathology revealed lacrimal myoepithelial carcinoma ex recurrent pleomorphic adenoma, T2N0M0. In addition, 18 cases of lacrimal myoepithelial tumor that have been previously described in the literature are reviewed. The application of clinical, radiological, histopathologic, and immunohistochemical investigations may help to reach the definite diagnosis. Criteria for malignancy of lacrimal myoepithelial tumor should be the same as salivary myoepithelial tumor diagnosis, until long-term outcome data for a larger number of patients with lacrimal myoepithelial carcinoma become available.


[Clinical experience with power-regulated contact laser surgery for the paranasal sinuses and the anterior skull base].
While laser surgical methods in Otorhinolaryngology have become widely established, their use in revision surgery for chronic-polypous sinusitis has been regarded as hazardous due to the vicinity of the anterior skull base and the orbit. However, new experience with laser-tissue interaction in contact irradiation together with effective power feedback control mechanisms require a re-evaluation of laser revision surgery in this field. After 742 primary, endonasal-microscopic sinus surgery procedures, 86 patients had 128 Nd:YAG-laser sessions performed within an interval of 1 - 24 months after primary surgery for recurrent polyposis, which had been irresponsive to medication. The maximum power delivered was 10 to 20 W. Recurrent polyposis appeared mostly in the maxillo-ethmoid angle, followed by the maxillary sinus roof and the maxillary sinus bottom. In 63 of 86 patients, no further polyposis was seen after laser surgery. If more than one laser session had to be performed, recurrent polyposis appeared in a different region in most cases. Those areas lasered first showed a reduced tendency to recurrence. There was moderate bleeding during laser surgery in 6 cases with reduced visibility, but no other serious complications were recorded. Laser surgery for chronic-polypous sinusitis is an alternative to conventional revision surgery, if medical treatment fails and recurrent polyposis is confined to certain regions. Feedback-controlled contact laser power delivery adds further therapeutic safety when applied next to the anterior skull base and the orbit.


A Case of an Elderly Woman Who Developed Corneal Perforation in the Clinical Course of Myeloperoxidase Positive Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is a systemic vasculitis characterized by ANCA positivity and categorized into three main types: microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatous with polyangiitis. Although AAV leads to systemic organ injury, such as of the lungs, kidneys, nerves, and skin, patients with AAV sometimes develop ocular lesions. Here, we report the case of an elderly woman who had been treated for AAV for seven years. She developed scleritis and relapsed twice, with elevation of serum disease markers such as ANCA titer and C-reactive protein. After the decline of these markers due to treatment with additional medication, her scleritis relapsed again and caused a corneal ulcer, which resulted in perforation without obvious marker elevation. She did not present with any symptoms of organ injury, except for ocular lesions. She was treated with surgery, followed by methylprednisolone and rituximab therapy. Subsequently, her ocular lesions and symptoms improved, and she did not relapse. AAV can cause various ocular manifestations. Although C-reactive protein and ANCA titers are useful markers of disease activity and the relapse of AAV complications, including ocular lesions, these markers do not always increase at the time of worsening ocular lesions. Therefore, it is important for clinicians treating patients with AAV to pay careful attention to serum data and physical findings, including the eyes.


Are trait self-control and self-control resources mediators of relations between executive functions and health behaviors?
This study investigated associations between executive functions (i.e., inhibition, working memory, cognitive flexibility) and individual differences in self-control and health behaviors. We examined whether executive functions predict physical activity, sedentary activity, and healthy and unhealthy diets, and whether trait self-control and self-control resources mediate these associations. Three hundred and eighty-five participants completed a questionnaire assessing trait self-control and self-control resources, physical activity, sedentary activity, and healthy and unhealthy diets. They also performed three randomly ordered cognitive tasks, a stop-signal task (i.e., inhibition), a letter memory task (i.e., updating), and a number-letter task (i.e., switching). Structural equation modeling revealed that self-control resources predicted positively physical activity (R2 = 0.08), negatively sedentary activity (R2 = 0.03) and positively healthy diet (R2 = 10). Moreover, trait self-control predicted positively healthy diet (R2 = 0.10) and negatively unhealthy diet (R2 = 0.19). Moreover, analyses revealed that switching significantly predicted self-control resources, and highlighted three totally mediated relations between this executive function and physical activity, sedentary activity and healthy diet. However, no evidence was found supporting associations between inhibition and updating, and health behaviors, or relations mediated by self-control for these executive functions. The findings suggest the importance of trait self-control and self-control resources for health behavior adoption and pave the way for studies exploring the role of the executive functions in an affective context. Open materials [https://osf.io/hpsjw/].


Natural and synthetic progestins enrich cancer stem cell-like cells in hormone-responsive human breast cancer cell populations in vitro.
Clinical trials and studies have shown that combination estrogen/progestin hormone replacement therapy, but not estrogen therapy alone or placebo, increases breast cancer risk in postmenopausal women. Using animal models, we have previously shown that both natural and synthetic progestins (including medroxyprogesterone acetate [MPA], a synthetic progestin used widely in the clinical setting) accelerate the development of breast tumors in vivo and increase their metastasis to lymph nodes. Based on these observations, we have hypothesized that progestin-induced breast cancer tumor growth and metastasis may be mediated by an enrichment of the cancer stem cell (CSC) pool. In this study, we used T47-D and BT-474 hormone-responsive human breast cancer cells to examine the effects of progestin on phenotypic and functional markers of CSCs in vitro. Both natural and synthetic progestins (10 nM) significantly increased protein expression of CD44, an important CSC marker in tumor cells. MPA increased the levels of both CD44 variants v3 and v6 associated with stem cell functions. This induction of CD44 was blocked by the antiprogestin RU-486, suggesting that this process is progesterone receptor (PR) dependent. CD44 induction was chiefly progestin dependent. Because RU-486 can bind other steroid receptors, we treated PR-negative T47-DCO-Y cells with MPA and found that MPA failed to induce CD44 protein expression, confirming that PR is essential for progestin-mediated CD44 induction in T47-D cells. Further, MPA treatment of T47-D cells significantly increased the activity of aldehyde dehydrogenase (ALDH), another CSC marker. Finally, two synthetic progestins, MPA and norethindrone, significantly increased the ability of T47-D cells to form mammospheres, suggesting that enrichment of the CD44high, ALDHbright subpopulation of cancer cells induced by MPA exposure is of functional significance. Based on our observations, we contend that exposure of breast cancer cells to synthetic progestins leads to an enrichment of the CSC pool, supporting the development of progestin-accelerated tumors in vivo.


Brain-stem afferents upon retinal projecting isthmo-optic and ectopic neurons of the pigeon centrifugal visual system demonstrated by retrograde transneuronal transport of rhodamine beta-isothiocyanate.
Brain-stem afferents to the n. isthmo-opticus (NIO) and ectopic neurons (EN) of the centrifugal visual system (CVS) were determined in the pigeon using the retrograde transneuronal transport of the fluorescent dye Rhodamine beta-isothiocyanate (RITC) after its intraocular injection. In other experiments, either RITC was injected into various periocular tissues (controls) or the retrograde tracer Fluoro-gold (FG) was injected stereotaxically in the NIO. Following intraocular injections, the RITC retrograde labeling of cell bodies was observed contralaterally in the NIO and EN and transneuronally in layers 9/10 of the optic tectum, area ventralis-Tsai, zona peri-NIII, mesencephalic and pontine reticular formation (PRF), n. linearis caudalis-raphe, and bilaterally within a region referred to as zona peri-n.NVI (Zp-n.NVI) immediately underlying the abducens nerve nucleus. None of the above structures were labeled after RITC periocular injections. The FG labeling revealed that the tectal efferent neurons were mainly medium-sized, multipolar cells whose dendrites extended superficially to retino-recipient tectal layers 6 and 5. Quantitative measurements of the distribution of layers 9/10 RITC-labeled neurons indicated the highest densities to be localized within the ventral tectum corresponding to the representation of the dorsal retina and inferior visual field. We suggest that visual and nonvisual brain-stem afferents upon NIO and EN may play a role in the proposed mechanism of the avian CVS in attention, ground-feeding behavior, and modulation of retinal sensitivity.


[Self-inflicted genital injury].
Self-inflicted injury to external genitalia in men is an uncommon type of trauma. The international and domestic literature report isolated cases of injury to the external genitalia, caused by a patient intending to harm himself. This type of injury often occurs in patients with mental disorders. The authors describe their own clinical observations of rare types of self-inflicted genital injuries in patients without a history of mental disorders. During the period from 2012 to 2015, 4 patients with self-inflicted genital injuries were admitted to the hospital. There was a penile self-amputation, self-orchiectomy, penile rupture, and foreskin cut wound. Despite the sufficient public awareness and availability of urological care in a large industrial city, cases of self-inflicted genital injury occur. In addition to medical care, such cases warrant psychological and possibly psychiatric counseling.


Evolution of the plant-microbe symbiotic 'toolkit'.
Beneficial associations between plants and arbuscular mycorrhizal fungi play a major role in terrestrial environments and in the sustainability of agroecosystems. Proteins, microRNAs, and small molecules have been identified in model angiosperms as required for the establishment of arbuscular mycorrhizal associations and define a symbiotic 'toolkit' used for other interactions such as the rhizobia-legume symbiosis. Based on recent studies, we propose an evolutionary framework for this toolkit. Some components appeared recently in angiosperms, whereas others are highly conserved even in land plants unable to form arbuscular mycorrhizal associations. The exciting finding that some components pre-date the appearance of arbuscular mycorrhizal fungi suggests the existence of unknown roles for this toolkit and even the possibility of symbiotic associations in charophyte green algae.


[Acute granulocytic leukaemia: prognostic value of medullary caryotype (author's transl)].
Thirty-nine cases of granulocytic acute leukaemia (AL) forming an homogeneous series were the object of a satisfactory chromosomal examination of the marrow by direct examination at the time of diagnosis. This group of patients was compared with another group of similar number where the conditions of patient referral, diagnosis and treatment were the same, in order to show that no selection was involved in the series studied. Medullary caryotype was found to be normal in 61,5% of cases. In such patients, the hope of complete remission and mean survival were significantly better than in cases where the caryotype was abnormal, and all the more so when the caryotype contained abnormalities in all the mitoses examined. For myeloblastic AL, the correlation between caryotype and the effects of treatment is very close (p less than 0,01). For the therapist, these results justify a new approach in the treatment of myeloblastic AL.


Crowder induced structural modulation of a multi-domain protein during its early stages of aggregation: A FRET-based and protein solvation study.
Protein aggregation has been known for long to be the prime cause for several neurological disorders in human beings. While protein aggregation is itself a complex process, understanding the same in the context of a crowded cellular medium remains a challenge. In this work, using Förster resonance energy transfer (FRET) and solvation dynamics, we have tried to gain important insights into the structural rearrangements, during the early stages of aggregation of the multidomain protein bovine serum albumin (BSA) in presence of a range of synthetic macromolecular crowding agents. FRET studies show that there is an initial compaction in the domain size (domain I) at the early time points of incubation followed by an increase in the distance between the donor-acceptor pair. Analyses of the solvent correlation traces of BADAN (labeled at free Cys-34 in domain I of BSA) reveal that the same domain becomes rigid during the initial phase of the aggregation process subsequent to which there was a gradual increase in flexibility, the latter we propose being a necessary step that allows facile addition of more protein units.


Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo.
The aim of this study is to investigate the clinical significance of hypoxia inducible factor-1α (HIF-1α) expression in esophageal squamous cell cancer (ESCC) and clarify the effects of PX-478, a selective HIF-1α inhibitor, on ESCC both in vitro and in vivo. HIF-1α, cyclooxygenase-2 (COX-2) and programmed death ligand-1 (PD-L1) were markedly overexpressed in ESCC tissue and associated with poorer survival. In vitro, both COX-2 and PD-L1 expression of ESCC cells were significantly induced by CoCl2 treatment, but inhibited by HIF-1α knock-down or PX-478 treatment. Furthermore, PX-478 significantly inhibited tumor cell proliferation by inhibiting the G2/M transition and promoting apoptosis of ESCC cells. In addition, inhibited epithelial-mesenchymal transition was observed after PX-478 treatment. In vivo, PX-478 significantly decreased tumor volume following subcutaneous implantation. Together, our results indicated that PX-478 had significant antitumor activity against HIF-1α over-expressing ESCC tumors in vitro and in vivo. These results opened up the possibility of inhibiting HIF-1α for targeted therapy of ESCC.


Impact of antifungal stewardship interventions on the susceptibility of colonized Candida species in pediatric patients with malignancy.
There is a worldwide concern regarding the antimicrobial resistance and the inappropriate use of antifungal agents, which had led to an ever-increasing antifungal resistance. This study aimed to identify the antifungal susceptibility of colonized Candida species isolated from pediatric patients with cancer and evaluate the clinical impact of antifungal stewardship (AFS) interventions on the antifungal susceptibility of colonized Candida species. Candida species colonization was evaluated among hospitalized children with cancer in a tertiary teaching hospital, Shiraz 2017-2018. Samples were collected from the mouth, nose, urine, and stool of the patients admitted to our center and cultured on sabouraud dextrose agar. The isolated yeasts identified by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). DNA Extracted and PCR amplification was performed using the ITS1 and ITS4 primer pairs and Msp I enzyme. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) for amphotericin B, caspofungin, and azoles. The prevalence of Candida albicans in the present study was significantly higher than other Candida species. Candida albicans species were completely susceptible to the azoles. The susceptibility rate of C. albicans to amphotericin B and caspofungin was 93.1% and 97.1%, respectively. The fluconazole MIC values of Candida albicans decreased significantly during the post-AFS period (P < 0.001; mean difference: 72.3; 95% CI of the difference: 47.36-98.62). We found that 52.5% (53/117) of the isolated C. albicans were azole-resistant before AFS implementation, while only 1.5% (2/102) of the isolates were resistant after implementation of the AFS program (P < 0.001). C. albicans fluconazole and caspofungin resistant rate also decreased significantly (P < 0.001) after implementation of the AFS program [26 (32.9%) versus 0 (0.0%) and 11 (10.9%) versus 1 (0.9%), respectively]. Besides, fluconazole use (p < 0.05) and fluconazole expenditure reduced significantly (about one thousand US$ per year) after the AFS program. Our results confirm the positive effect of optimized antifungal usage and bedside intervention on the susceptibility of Candida species after the implementation of the AFS program. C. albicans and C. glabrata exhibited a significant increase in susceptibility after the execution of the AFS program.


The Barriers to Deprescription in Older Patients: A Survey of Spanish Clinicians.
There are barriers to deprescription that hinder its implementation in clinical practice. The objective of this study was to analyse the main barriers and limitations of the deprescription process perceived by physicians who care for multipathological patients. The "deprescription questionnaire of elderly patients" was adapted to an online format and sent to physicians in geriatrics. Question 1 is a reference to establish agreement or disagreement with this practice. The influence of different aspects of deprescription was analysed via the demographic characteristics of the clinicians and perceptions of the various barriers (questions 2-9) by means of bivariate analysis. Based on the latter, a multivariate model was carried out to demonstrate the relationship between barriers and the degree of deprescription agreement among respondents. Of the 72 respondents, 72.2% were in favour of deprescribing. Regarding the analyses, the demographic characteristics did not influence rankings. The deprescription of preventive drugs and consensus with patients were associated with a positive attitude towards deprescribing, while withdrawing drugs prescribed by other professionals, time constraints and patient reluctance emerged as possible barriers. The only factor independently associated with deprescribing was lack of time. Time was found to be the main barrier to deprescription. Training, the creation of multidisciplinary teams and integrated health systems are key facilitators.


Thoracoscopic treatment of pulmonary hydatid cyst in children: a report of 25 cases.
Open surgery is the standard option for the treatment of hydatid pulmonary cysts. Surgeons are able to replicate the principles of conventional surgery using minimally invasive techniques ,in particular thoracoscopy. However, there are few reports about this subject in children. To our knowledge, this is one of the biggest pediatric series ever reported in the literature. aim: the purpose of this study was to determine the best indications of the thoracospic surgery for the treatment of the pulmonary hydatid cysts in children. methods: We report a series of 25 cases with pulmonary hydatid cysts treated using the thoracoscopic approach from 2005 to 2009. We retrospectively analyzed the patients' sex, age, symptoms, biological data, characteristics of hydatid cysts (location, number and size) and the medical treatments. Pulmonary hydatid cyst diagnosis was performed on Chest x-ray, abdominal ultrasound and biological data in all the cases. Tomography was not systematic. All patients underwent video-assisted surgery. A conversion to thoracotomy was conducteded in 2 cases. All the patients had a chest tube and received an antibio-prophylaxy , without Albendazol . A concurrent hydatid cyst at the opposite lung or in the peritoneal cavity was treated later. results: There were 25 cases with a sex ratio of 2.1 and a mean age of 8 years. All the patients underwent a video-assisted surgery. A conversion to thoracotomy was performed in 2 cases because hydatid cysts were large (size > 8 cm). The average duration of the procedure was 75 minutes. In the post-operative course, one patient presented an air leak which required a prolonged chest drainage for 16 days and a second one was treated for lung infection. In all the other cases, the follow-up was uneventful. The thoracoscopic approach for pulmonary hydatid cysts in children is feasible. For better results, it is recommended for cysts smaller than 5 cm.


Prevalence and risk factors for HIV, hepatitis B, and hepatitis C in people with severe mental illness: a total population study of Sweden.
Severe mental illness is associated with increased morbidity and mortality. The elevated risk of blood-borne viruses (BBVs) in people with severe mental illness is of concern, but the full extent of this problem is unclear. We aimed to determine the prevalence of and risk factors for BBVs in people with severe mental illness. In this nationwide, population-based, cross-sectional study, we estimated the point prevalence of HIV, hepatitis B (HBV), and hepatitis C (HCV) in people with severe mental illness, including the total adult (≥18 years) Swedish population. We defined severe mental illness as a clinical diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or other psychotic illness according to the Swedish version of the International Statistical Classification of Diseases version 8, 9, or 10. We used multivariable logistic regression to determine the odds of BBVs in individuals with severe mental illness, relative to the general population, and to identify independent risk factors (age, sex, immigration status, socioeconomic status, education, and substance misuse) for BBV infection. We also did a sensitivity analysis excluding BBV diagnoses made before the introduction of the Register for Infection Disease Control (1997). Of 6 815 931 adults in Sweden, 97 797 (1·43%) individuals had a diagnosis of severe mental illness. Prevalence of BBVs was elevated in people with severe mental illness, of which 230 (0·24%) had HIV, 518 (0·53%) had HBV, and 4476 (4·58%) had HCV. After accounting for sociodemographic characteristics, the odds of HIV were 2·57 (95% CI 2·25-2·94, p<0·0001) times higher in people with severe mental illness than in the general population, whereas the odds of HBV were 2·29 (2·09-2·51, p<0·0001) times higher and the odds of HCV were 6·18 (5·98-6·39, p<0·0001) times higher. Substance misuse contributed most to the increased risk of BBV: after adjustment, odds ratios were 1·61 (1·40-1·85, p<0·0001) for HIV, 1·28 (1·16-1·41, p<0·0001) for HBV, and 1·72 (1·67-1·78, p<0·0001) for HCV. Our results highlight the need to address the issue of higher prevalence of BBVs in people with severe mental illness and identify interventions preventing infection. Targeting of comorbid substance misuse would have particular effect on reduction of BBV prevalence in this population. Medical Research Council and Swedish Research Council.


Characterization of a New Cold-Adapted and Salt-Activated Polysaccharide Lyase Family 7 Alginate Lyase from Pseudoalteromonas sp. SM0524.
Marine bacterial alginate lyases play a role in marine alginate degradation and carbon cycling. Although a large number of alginate lyases have been characterized, reports on alginate lyases with special characteristics are still rather less. Here, a gene alyPM encoding an alginate lyase of polysaccharide lyase family 7 (PL7) was cloned from marine Pseudoalteromonas sp. SM0524 and expressed in Escherichia coli. AlyPM shows 41% sequence identity to characterized alginate lyases, indicating that AlyPM is a new PL7 enzyme. The optimal pH for AlyPM activity was 8.5. AlyPM showed the highest activity at 30°C and remained 19% of the highest activity at 5°C. AlyPM was unstable at temperatures above 30°C and had a low T m of 37°C. These data indicate that AlyPM is a cold-adapted enzyme. Moreover, AlyPM is a salt-activated enzyme. AlyPM activity in 0.5-1.2 M NaCl was sixfolds higher than that in 0 M NaCl, probably caused by a significant increase in substrate affinity, because the K m of AlyPM in 0.5 M NaCl decreased more than 20-folds than that in 0 M NaCl. AlyPM preferably degraded polymannuronate and mainly released dimers and trimers. These data indicate that AlyPM is a new PL7 endo-alginate lyase with special characteristics.


Impact of body composition on performance in fitness tests among personnel of the Croatian navy.
The purpose of this study was to determine the impact of body weight on fitness tests among the personnel of the Croatian navy. Forty two naval personnel (age 27 +/- 4.1 years; body mass 86.2 +/- 4.9 kg; height 184.6 +/- 7.4 cm; body fat percentage 17.3 +/- 5.2) participated in this study. In order to evaluate the fitness of the naval servicemen, we applied a testing procedure that included measurements of 7 fitness tests and 15 body anthropometric tests. A negative correlation was found between the body fat percentage and all the analyzed sprint tests and three anaerobic power tests (r), SP5 (r = -0.42), SP10 (r = -0.51), SP20 (r = -0.53), SJ (r = -0.45), CM (r = -0.57), SLJ (r = -0.67). Also a negative correlation was found between the body fat percentage and VO2(max) (r = -0.44). A positive correlation was found between the sprint test and the power performance test and thigh and calf girth. Spiriting ability is influenced by the strength of a person. This is one of the reasons why we found a positive correlation between the sprint test (SP5, SP10 and SP20) and thigh and calf girth. In this study we found a negative correlation between body fat percentages and all the sprint tests and three anaerobic power tests and VO2(max). The ectomorph somatotypes have positive correlations with all variables. The mesomorph somatotypes have the greatest positive correlations with all variables. The endomorph somatotypes have negative correlations with all variables. According to the body composition of Croatian naval servicemen we can conclude that they need a sufficient level of strength and endurance for everyday tasks. The effectiveness of a weight-management program is determined by the success of the participants in losing the necessary amount of weight and being able to maintain that weight loss. This requires long-term tracking of these individuals in a naval environment.


Efficient Gas Barrier and Antibacterial Properties of Poly(lactic acid) Nanocomposites: Functionalization with Phytic Acid-Cu(II) Loaded Layered Clay.
Poly(lactic acid) (PLA) represents one of the most promising and attractive bio-based polymers for green packaging. However, toughness, gas barrier and antibacterial properties of pure PLA films cannot compete with those of traditional petroleum-based active packaging plastics. To fill this gap, utilization of excellent chelating properties of phytic acid (PA), functionalized layered double hydroxides (LDHs@PA-Cu(II)) was firstly synthetized via facile deposition and chelation of one-step assembled PA-Cu(II) coordination compounds on the surface of layered clay. Furthermore, LDHs@PA-Cu(II)/PLA nanocomposites were prepared by blending LDHs@PA-Cu(II) and pure PLA via solution casting evaporation process. After adding only 1 wt % LDHs@PA-Cu(II), elongation at break and tensile strength increase by 53.0% and 18.9%, respectively, and the oxygen relative permeability decreases by 28.0%. Due to the strong interface interaction and heterogenous nucleation, the reinforcement effect of LDHs@PA-Cu(II) at low loadings is remarkable. Meanwhile, owing to the antibacterial activity of PA-Cu(II) coatings, the antibacterial rate (against Escherichia coli) of LDHs@PA-Cu(II) exceeds 99.99%. Furthermore, the corresponding LDHs@PA-Cu(II)/PLA nanocomposites also show outstanding antibacterial properties, which will be a promising candidate for active packaging application.


Joint Attention During Live Person-to-Person Contact Activates rTPJ, Including a Sub-Component Associated With Spontaneous Eye-to-Eye Contact.
Eye-to-eye contact is a spontaneous behavior between interacting partners that occurs naturally during social interactions. However, individuals differ with respect to eye gaze behaviors such as frequency of eye-to-eye contacts, and these variations may reflect underlying differences in social behavior in the population. While the use of eye signaling to indicate a shared object of attention in joint attention tasks has been well-studied, the effects of the natural variation in establishing eye contact during joint attention have not been isolated. Here, we investigate this question using a novel two-person joint attention task. Participants were not instructed regarding the use of eye contacts; thus all mutual eye contact events between interacting partners that occurred during the joint attention task were spontaneous and varied with respect to frequency. We predicted that joint attention systems would be modulated by differences in the social behavior across participant pairs, which could be measured by the frequency of eye contact behavior. We used functional near-infrared spectroscopy (fNIRS) hyperscanning and eye-tracking to measure the neural signals associated with joint attention in interacting dyads and to record the number of eye contact events between them. Participants engaged in a social joint attention task in which real partners used eye gaze to direct each other's attention to specific targets. Findings were compared to a non-social joint attention task in which an LED cue directed both partners' attention to the same target. The social joint attention condition showed greater activity in right temporoparietal junction than the non-social condition, replicating prior joint attention results. Eye-contact frequency modulated the joint attention activity, revealing bilateral activity in social and high level visual areas associated with partners who made more eye contact. Additionally, when the number of mutual eye contact events was used to classify each pair as either "high eye contact" or "low eye contact" dyads, cross-brain coherence analysis revealed greater coherence between high eye contact dyads than low eye contact dyads in these same areas. Together, findings suggest that variation in social behavior as measured by eye contact modulates activity in a subunit of the network associated with joint attention.


A new mouse gene, SRG3, related to the SWI3 of Saccharomyces cerevisiae, is required for apoptosis induced by glucocorticoids in a thymoma cell line.
We isolated a new mouse gene that is highly expressed in thymocytes, testis, and brain. This gene, SRG3, showed a significant sequence homology to SWI3, a yeast transcriptional activator, and its human homolog BAF155. SRG3 encodes 1,100 amino acids and has 33-47% identity with SWI3 protein over three regions. The SRG3 protein contains an acidic NH2 terminus, a myb-like DNA binding domain, a leucine-zipper motif, and a proline- and glutamine-rich region at its COOH terminus. Rabbit antiserum raised against a COOH-terminal polypeptide of the SRG3 recognized a protein with an apparent molecular mass of 155 kD. The serum also detected a 170-kD protein that seems to be a mouse homologue of human BAF170. Immunoprecipitation of cell extract with the antiserum against the mouse SRG3 also brought down a 195-kD protein that could be recognized by an antiserum raised against human SWI2 protein. The results suggest that the SRG3 protein associates with a mouse SWI2. The SRG3 protein is expressed about three times higher in thymocytes than in peripheral lymphocytes. The expression of anti-sense RNA to SRG3 mRNA in a thymoma cell line, S49.1, reduced the expression level of the SRG3 protein, and decreased the apoptotic cell death induced by glucocorticoids. These results suggest that the SRG3 protein is involved in the glucocorticoid-induced apoptosis in the thymoma cell line. This implicates that the SRG3 may play an important regulatory role during T cell development in thymus.


Periodontitis diabetica. A case report from Nigeria.
A 16-year-old female presented with severe chronic periodontitis and previously unsuspected diabetes mellitus. Her diabetes was mild initially. As the periodontitis improved with antibiotics, het diabetic control worsened because she was able to eat more. In the light of their personal observations and this case report, the authors believe there to be a direct association between diabetes mellitus and periodontitis.


Early induction of apple fruitlet abscission is characterized by an increase of both isoprene emission and abscisic acid content.
Apple (Malus domestica) fruitlet abscission represents an interesting model system to study the early phases of the shedding process, during which major transcriptomic changes and metabolic rearrangements occur within the fruit. In apple, the drop of fruits at different positions within the cluster can be selectively magnified through chemical thinners, such as benzyladenine and metamitron, acting as abscission enhancers. In this study, different abscission potentials were obtained within the apple fruitlet population by means of the above-cited thinners. A metabolomic study was conducted on the volatile organic compounds emitted by abscising fruitlets, allowing for identification of isoprene as an early marker of abscission induction. A strong correlation was also observed between isoprene production and abscisic acid (ABA) levels in the fruit cortex, which were shown to increase in abscising fruitlets with respect to nonabscising ones. Transcriptomic evidence indicated that abscission-related ABA is biologically active, and its increased biosynthesis is associated with the induction of a specific ABA-responsive 9-cis-epoxycarotenoid dioxygenase gene. According to a hypothetical model, ABA may transiently cooperate with other hormones and secondary messengers in the generation of an intrafruit signal leading to the downstream activation of the abscission zone. The shedding process therefore appears to be triggered by multiple interdependent pathways, whose fine regulation, exerted within a very short temporal window by both endogenous and exogenous factors, determines the final destiny of the fruitlets.


How to evaluate whether a new technology in the operating room is cost-effective from society's viewpoint.
The hospital operating room is one of the most important and costly environments in health care. Given the current reductions in reimbursement and limited resources, hospital administrators and operating room managers have to be careful about adopting new technologies into the operating room. Operating rooms must balance the improved care a new technology can provide with its additional costs. Economic analysis provides systematic methods to guide decisions by quantitatively assessing the value of a new technology.


Atf1 is a target of the mitogen-activated protein kinase Pmk1 and regulates cell integrity in fission yeast.
In fission yeast, knockout of the calcineurin gene resulted in hypersensitivity to Cl(-), and the overexpression of pmp1(+) encoding a dual-specificity phosphatase for Pmk1 mitogen-activated protein kinase (MAPK) or the knockout of the components of the Pmk1 pathway complemented the Cl(-) hypersensitivity of calcineurin deletion. Here, we showed that the overexpression of ptc1(+) and ptc3(+), both encoding type 2C protein phosphatase (PP2C), previously known to inactivate the Wis1-Spc1-Atf1 stress-activated MAPK signaling pathway, suppressed the Cl(-) hypersensitivity of calcineurin deletion. We also demonstrated that the mRNA levels of these two PP2Cs and pyp2(+), another negative regulator of Spc1, are dependent on Pmk1. Notably, the deletion of Atf1, but not that of Spc1, displayed hypersensitivity to the cell wall-damaging agents and also suppressed the Cl(-) hypersensitivity of calcineurin deletion, both of which are characteristic phenotypes shared by the mutation of the components of the Pmk1 MAPK pathway. Moreover, micafungin treatment induced Pmk1 hyperactivation that resulted in Atf1 hyperphosphorylation. Together, our results suggest that PP2C is involved in a negative feedback loop of the Pmk1 signaling, and results also demonstrate that Atf1 is a key component of the cell integrity signaling downstream of Pmk1 MAPK.


Association Between Anger and Mortality in Women and Men: A Prospective Cohort Study in a Japanese Community.
Background: Anger is a common problem in society, and anger's relationship with mortality, in particular with cardiovascular mortality, has been studied mainly in male western population. There are no prospective studies in Japan, about the association between anger and mortality. Materials and Methods: This study examined the association of anger with all-cause and cause-specific mortality in a Japanese community. Data came from the Takayama Study, which recruited residents aged ≥35 years in 1992 from Takayama City in Gifu, Japan. The current study used information on anger that was obtained from the second survey in 2002. A total of 11,902 healthy participants aged ≥45 years completed a self-administered questionnaire. Anger was assessed using the Spielberger Trait Anger Scale. Results: The main causes of deaths during the follow-up period from 2002 to 2013 were 460 for neoplasm, 254 for cardiovascular, and 435 for other causes. After adjusting for potential confounders, we found a significant positive association between the trait anger score and the risk of cardiovascular mortality for women, with a hazard ratio for high versus low score of trait anger of 1.81 (95% confidence interval 0.91-3.63, p for trend = 0.04), but not for men. Conclusions: Data suggest that for Japanese women, high trait anger score may be associated with an increased risk of cardiovascular mortality. Potential gender differences in the association between trait anger and mortality should be further studied from the cultural context.


Resistance exercise improves physical fatigue in women with fibromyalgia: a randomized controlled trial.
Fibromyalgia (FM) affects approximately 1-3 % of the general population. Fatigue limits the work ability and social life of patients with FM. A few studies of physical exercise have included measures of fatigue in FM, indicating that exercise can decrease fatigue levels. There is limited knowledge about the effects of resistance exercise on multiple dimensions of fatigue in FM. The present study is a sub-study of a multicenter randomized controlled trial in women with FM. The purpose of the present sub-study was to examine the effects of a person-centered progressive resistance exercise program on multiple dimensions of fatigue in women with FM, and to investigate predictors of the potential change in fatigue. A total of 130 women with FM (age 22-64 years) were included in this assessor-blinded randomized controlled multicenter trial examining the effects of person-centered progressive resistance exercise compared with an active control group. The intervention was performed twice a week for 15 weeks. Outcomes were five dimensions of fatigue measured with the Multidimensional Fatigue Inventory (MFI-20). Information about background was collected and the women also completed several health-related questionnaires. Multiple linear stepwise regression was used to analyze predictors of change in fatigue in the total population. A higher improvement was found at the post-treatment examination for change in the resistance exercise group, as compared to change in the active control group in the MFI-20 subscale of physical fatigue (resistance group Δ -1.7, SD 4.3, controls Δ 0.0, SD 2.7, p = 0.013), with an effect size of 0.33. Sleep efficiency was the strongest predictor of change in the MFI-20 subscale general fatigue (beta = -0.54, p = 0.031, R (2) = 0.05). Participating in resistance exercise (beta = 1.90, p = 0.010) and working fewer hours per week (beta = 0.84, p = 0.005) were independent significant predictors of change in physical fatigue (R (2) = 0.14). Person-centered progressive resistance exercise improved physical fatigue in women with FM when compared to an active control group. ClinicalTrials.gov NCT01226784 . Registered 21 October 2010.


Nuclear HuR accumulation through phosphorylation by Cdk1.
A predominantly nuclear RNA-binding protein, HuR translocates to the cytoplasm in response to stress and proliferative signals, where it stabilizes or modulates the translation of target mRNAs. Here, we present evidence that HuR phosphorylation at S202 by the G2-phase kinase Cdk1 influences its subcellular distribution. HuR was specifically phosphorylated in synchronous G2-phase cultures; its cytoplasmic levels increased by Cdk1-inhibitory interventions and declined in response to Cdk1-activating interventions. In keeping with the prominently cytoplasmic location of the nonphosphorylatable point mutant HuR(S202A), phospho-HuR(S202) was shown to be predominantly nuclear using a novel anti-phospho-HuR(S202) antibody. The enhanced cytoplasmic presence of unphosphorylated HuR was linked to its decreased association with 14-3-3 and to its heightened binding to target mRNAs. Our findings suggest that Cdk1 phosphorylates HuR during G2, thereby helping to retain it in the nucleus in association with 14-3-3 and hindering its post-transcriptional function and anti-apoptotic influence.


Are Histidine Kinases of Arbuscular Mycorrhizal Fungi Involved in the Response to Ethylene and Cytokinins?
Signals are exchanged at all stages of the arbuscular mycorrhizal (AM) symbiosis between fungi and their host plants. Root-exuded strigolactones are well-known early symbiotic cues, but the role of other phytohormones as interkingdom signals has seldom been investigated. Here we focus on ethylene and cytokinins, for which candidate receptors have been identified in the genome of the AM fungus Rhizophagus irregularis. Ethylene is known from the literature to affect asymbiotic development of AM fungi, and in the present study, we found that three cytokinin forms could stimulate spore germination in R. irregularis. Heterologous complementation of a Saccharomyces cerevisiae mutant strain with the candidate ethylene receptor RiHHK6 suggested that this protein can sense and transduce an ethylene signal. Accordingly, its N-terminal domain expressed in Pichia pastoris displayed saturable binding to radiolabeled ethylene. Thus, RiHHK6 displays the expected characteristics of an ethylene receptor. In contrast, the candidate cytokinin receptor RiHHK7 did not complement the S. cerevisiae mutant strain or Medicago truncatula cytokinin receptor mutants and seemed unable to bind cytokinins, suggesting that another receptor is involved in the perception of these phytohormones. Taken together, our results support the hypothesis that AM fungi respond to a range of phytohormones and that these compounds bear multiple functions in the rhizosphere beyond their known roles as internal plant developmental regulators. Our analysis of two phytohormone receptor candidates also sheds new light on the possible perception mechanisms in AM fungi. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Interrater Reliability Testing of the Maternal Fetal Triage Index.
To conduct interrater reliability testing of the Maternal Fetal Triage Index (MFTI), a standardized tool for obstetric triage. Observational study of a convenience sample of nurses' triage assessments of hospital-based obstetric patients. A birth unit of a suburban hospital located in a large metropolitan region with approximately 5,200 births annually. Ten registered nurses provided triage assessments of 211 pregnant women. Using blinded paired triage assessments, we assessed the reproducibility of the triage priority levels assigned using the MFTI. Priority levels assigned by the MFTI research nurse and the study nurses were in agreement for 154 of the 211 (72.9%) triage assessments. The strength of agreement was classified as good based upon the weighted kappa score of 0.65. There was no statistically significant difference in the accuracy of assigning priority levels between the day and night shifts The interrater reliability of the MFTI met the minimum strength of agreement threshold goal of 0.60 when used by nurses in a large birth unit to assign priority for evaluation. Based on this finding, the MFTI can be recommended for use in obstetric triage settings. Additional testing should be done to measure how this standardized tool improves care processes and outcomes.