Ultrasonic Removal of Mucilage for Pressurized Liquid Extraction of Omega-3 Rich Oil from Chia Seeds (Salvia hispanica L.).
Chia (Salvia hispanica L.) seeds contain an important amount of edible oil rich in omega-3 fatty acids. Fast and alternative extraction techniques based on polar solvents, such as ethanol or water, have become relevant for oil extraction in recent years. However, chia seeds also contain a large amount of soluble fiber or mucilage, which makes difficult an oil extraction process with polar solvents. For that reason, the aim of this study was to develop a gentle extraction method for mucilage in order to extract chia oil with polar solvents using pressurized liquids and compare with organic solvent extraction. The proposed mucilage extraction method, using an ultrasonic probe and only water, was optimized at mild conditions (50 °C and sonication 3 min) to guarantee the omega-3 oil quality. Chia oil extraction was performed using pressurized liquid extraction (PLE) with different solvents and their mixtures at five different extraction temperatures (60, 90, 120, 150, and 200 °C). Optimal PLE conditions were achieved with ethyl acetate or hexane at 90 °C in only 10 min of static extraction time (chia oil yield up to 30.93%). In addition, chia oils extracted with nonpolar and polar solvents by PLE were analyzed by gas chromatography-mass spectrometry (GC-MS) to evaluate fatty acid composition at different extraction conditions. Chia oil contained ∼65% of α-linolenic acid regardless of mucilage extraction method, solvent, or temperature used. Furthermore, tocopherols and tocotrienols were also analyzed by HPLC in the extracted chia oils. The mucilage removal allowed the subsequent extraction of the chia oil with polar or nonpolar solvents by PLE producing chia oil with the same fatty acid and tocopherol composition as traditional extraction.


The relationship between self-efficacy and student physician assistant clinical performance.
The purpose of this study was to investigate the predictive relationship between student self-efficacy beliefs, achievement expectations, perceived outcome values, and subsequent clinical performance. The study investigated whether measures of self-efficacy, measures of achievement expectancy, or measures of perceived task value (relevance) correlated significantly with physician assistant clinical performance; also, it investigated whether utilizing both noncognitive criteria and cognitive criteria will improve upon the predictability of physician assistant clinical performance. The independent variables include grade point average, previous health care experience, self-efficacy, values, and outcome expectations. The research population comprised a group of approximately 300 students attending the 14 accredited programs within Pennsylvania who, at the time of the surveys, were beginning the clinical year of their professional education. Data collection methods included surveys and quantitative data sources. The data were subjected to multivariate statistical methods including multiple regression and discriminate analysis. The analysis included both correlation and regression to predict clinical performance from the noncognitive and cognitive variables. The results reveal that self-efficacy, and not just academic performance, is a significant predictor of a student's clinical performance. Utilizing both noncognitive and cognitive variables can improve upon the predictability of the student physician assistant's clinical performance.


A comprehensive program to prevent pressure ulcers in long-term care: exploring costs and outcomes.
With scrutiny from survey agencies (Centers for Medicare and Medicaid Services and state agencies) and potential litigation increasing, long-term care facilities must implement aggressive pressure ulcer prevention programs. However, cost-effective pressure ulcer prevention continues to be a challenge for most long-term care facilities, in part because limited research is available to guide their efforts. Two long-term care facilities (Facility A with 150 beds and Facility B with 110 beds) participated in a quasi-experimental study using retrospective and prospective study data to evaluate the effect of implementing a protocol of care to address the incidence of pressure ulcers. Retrospective study results showed a combined, cumulative, 5-month pressure ulcer incidence of 43% in Facilities A and B. Implementation of the comprehensive prevention program resulted in an 87% decrease in pressure ulcer incidence in Facility A (from 13.2% to 1.7% per month, P = 0.02) and a 76% decrease in Facility B (from 15% to 3.5% per month, P = 0.02). The average monthly cost of prevention for a high-risk resident was $519.73 (plus a one time cost of $277 for mattress and chair overlays). More than half ($277.15) of the monthly costs relates to labor; the most expensive item cost is for support surfaces. This study demonstrated that this comprehensive program resulted in a significant decrease in the incidence of pressure ulcers in two long-term care facilities. Because labor and support surface costs remain high, long-term care facilities are encouraged to use prevention intervention strategies based on risk stratification.


Systematic identification of functionally relevant risk alleles to stratify aggressive versus indolent prostate cancer.
Novel approaches for classification, including molecular features, are needed to direct therapy for men with low-grade prostate cancer (PCa), especially men on active surveillance. Risk alleles identified from genome-wide association studies (GWAS) could improve prognostication. Those risk alleles that coincided with genes and somatic copy number aberrations associated with progression of PCa were selected as the most relevant for prognostication. In a systematic literature review, a total of 698 studies were collated. Fifty-three unique SNPs residing in 29 genomic regions, including 8q24, 10q11 and 19q13, were associated with PCa progression. Functional studies implicated 21 of these single nucleotide polymorphisms (SNPs) as modulating the expression of genes in the androgen receptor pathway and several other oncogenes. In particular, 8q24, encompassing MYC, harbours a high density of SNPs conferring unfavourable pathological characteristics in low-grade PCa, while a copy number gain of MYC in low-grade PCa was associated with prostate-specific antigen recurrence after radical prostatectomy. By combining GWAS data with gene expression and structural rearrangements, risk alleles were identified that could provide a new basis for developing a prognostication tool to guide therapy for men with early prostate cancer.


Physical effects of negative air ions in a wet sauna.
The physical effects of negative air ions on humans were determined in an experimental sauna room equipped with an ionizer. Thirteen healthy persons took a wet sauna bath (dry bulb temperature 42 degrees C, relative humidity 100%, 10 min exposure) with or without negative air ions. The subjects were not told when they were being exposed to negative air ions. There were no differences in the moods of these persons or changes in their blood pressures between the two saunas. The surface temperatures of the foreheads, hands, and legs in the sauna with negative ions were significantly higher than those in the sauna without ions. The pulse rates and sweat produced in the sauna with ions were significantly higher than those in the sauna without ions. The results suggest that negative ions may amplify the effects on humans of the sauna.


Divergence of Stp1 and Stp2 transcription factors in Candida albicans places virulence factors required for proper nutrient acquisition under amino acid control.
Candida albicans possesses a plasma membrane-localized sensor of extracellular amino acids. Here, we show that in response to amino acids, this sensor induces the proteolytic processing of two latent transcription factors, Stp1 and Stp2. Processing removes negative regulatory motifs present in the N-terminal domains of these factors. Strikingly, Stp1 and Stp2 exhibit a clear dichotomy in the genes they transactivate. The shorter active form of Stp2 activates genes required for amino acid uptake. The processed form of Stp1 activates genes required for degradation of extracellular protein and uptake of peptides, and cells lacking Stp1 do not express the secreted aspartyl protease SAP2 or the oligopeptide transporter OPT1. Consequently, stp1 null mutants are unable to grow on media with protein as the sole nitrogen source. Cells expressing the STP1* allele that encodes a protein lacking the inhibitory N-terminal domain constitutively express SAP2 and OPT1 even in the absence of extracellular proteins or peptides. Also, we show that Stp1 levels, but not Stp2 levels, are downregulated in the presence of millimolar concentrations of extracellular amino acids. These results define the hierarchy of regulatory mechanisms that differentially control two discrete pathways for the assimilation of nitrogen.


Relationship between amount of beta-blockers permeating through the stratum corneum and skin irritation after application of beta-blocker adhesive patches to guinea pig skin.
We evaluated the relationship between the cumulative amounts of 5 kinds of beta-blockers (alprenolol, oxprenolol, timolol, acebutolol and atenolol) permeating through the stratum corneum and a* values obtained by measuring the formation of erythema, a skin irritation reaction, with a chromameter after transdermal application of adhesive patches containing 2 beta-blocker to the skin of guinea pigs. The cumulative amount of beta-blocker released from each adhesive patch to the skin increased with the increase in application time. The contents of alprenolol, oxprenolol and timolol in the stratum corneum and in the stripped skin increased markedly up to 4 h after application and thereafter were maintained at high levels up to 24 h. The contents of acebutolol and atenolol, on the other hand, increased up to 24 h, but these values were low. a* values of all adhesive patches 24 h after application were higher than those before application. The correlation coefficients between the cumulative amounts of alprenolol, oxprenolol, timolol, acebutolol or atenolol permeating through the stratum corneum and (delta a* -delta a*Placebo) values were 0.739, 0.717, 0.722, 0.551 and 0.633, respectively. The correlation coefficient calculated by averaging the cumulative amounts of 6 kinds of beta-blockers permeating through the stratum corneum [including propranolol which was reported previously (Kobayashi I., et al., Biol. Pharm. Bull., 19, 839-844 (1996))] was 0.731, higher than the correlation coefficient between contents of these beta-blockers in the stripped skin and (delta a* -delta a*Placebo) values (r = 0.552). This suggests that there was a high correlation between the cumulative amounts of beta-blockers permeating through the stratum corneum and (delta a* -delta a*Placebo) values.


In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways.
Two pairs of ceftolozane/tazobactam susceptible/resistant P. aeruginosa were isolated from 2 patients after exposure to β-lactams. The genetic basis of ceftolozane/tazobactam resistance was evaluated, and β-lactam-resistant mechanisms were assessed by phenotypic assays. Whole genome sequencing identified mutations in AmpC including the mutation (V213A) and a deletion of 7 amino acids (P210-G216) in the Ω-loop. Phenotypic assays showed that ceftolozane/tazobactam resistance in the strain with AmpCV213A variant was associated with increased β-lactamase hydrolysis activity. On the other hand, the deletion of 7 amino acids in the Ω-loop of AmpC did not display enhanced β-lactamase activity. Resistance to ceftolozane/tazobactam in P. aeruginosa is associated with changes in AmpC; however, the apparent loss of β-lactamase activity in AmpC∆7 suggests that non-AmpC mechanisms could play an important role in resistance to β-lactam/β-lactamase inhibitor combinations.


Reconstruction of eyelid defects: a prefabricated multilayer sandwich graft.
We have developed a new technique for reconstruction of full thickness eyelid defects. A composite three-layer skin-cartilage-mucosal unit is manufactured and tailored three-dimensionally. Use of this sandwich graft in our patients proved to be simple and safe for eyelid reconstruction and has given good results without complications in four patients.


Ethylene Improves Root System Development under Cadmium Stress by Modulating Superoxide Anion Concentration in Arabidopsis thaliana.
This work aims at identifying the effects of ethylene on the response of Arabidopsis thaliana root system to cadmium chloride (CdCl2) stress. Two ethylene-insensitive mutants, ein2-5 and ein3-1eil1-1, were subjected to (25, 50, 75, and 100 μM) CdCl2 concentrations, from which 75 μM concentration decreased root growth by 40% compared with wild type Col-0 as a control. Ethylene biosynthesis increased in response to CdCl2 treatment. The length of primary root and root tip in ein2-5 and ein3-1eil1-1 decreased compared with wild type after CdCl2 treatment, suggesting that ethylene play a role in root system response to Cd stress. The superoxide concentration in roots of ein2-5 and ein3-1eil1-1 was greater than in wild type seedlings under Cd stress. Application of exogenous 1-aminocyclopropane-1-carboxylic acid (ACC) (a precursor of ethylene biosynthesis) in different concentrations (0.01, 0.05 and 0.5 μM) decreased superoxide accumulation in Col-0 root tips and increased the activities of superoxide dismutase (SOD) isoenzymes under Cd stress. This result was reversed with 5 μM of aminoisobutyric acid AIB (an inhibitor of ethylene biosynthesis). Moreover, it was accompanied by increase in lateral roots number and root hairs length, indicating the essential role of ethylene in modulating root system development by controlling superoxide accumulation through SOD isoenzymes activities. The suppressed Cd-induced superoxide accumulation in wild type plants decreased the occurrence of cells death while programmed cell death (PCD) was initiated in the root tip zone, altering root morphogenesis (decreased primary root length, more lateral roots and root hairs) to minimize the damage caused by Cd stress, whereas this response was absent in the ein2-5 and ein3-1eil1-1 seedlings. Hence, ethylene has a role in modulating root morphogenesis during CdCl2 stress in A. thaliana by increasing the activity of SOD isoenzymes to control superoxide accumulation.


A new diketopiperazine heterodimer from an endophytic fungus Aspergillus niger.
One new diketopiperazine heterodimer, asperazine A (1), and eight known compounds, asperazine (2), cyclo(d-Phe-l-Trp) (3), cyclo(l-Trp-l-Trp) (4), 4-(hydroxymethyl)-5,6-dihydro-pyran-2-one (5), walterolactone A (6), and campyrones A-C (7-9), were isolated from an endophytic fungus Aspergillus niger. Their structures were determined unequivocally on the basis of extensive spectroscopic data analysis. This is the first report of the presence of compound 3 as a natural product. Cytotoxicity test against human cancer cell lines PC3, A2780, K562, MBA-MD-231, and NCI-H1688 revealed that compounds 1 and 2 had weak activities.


Antibiotic use in endodontic treatment during pregnancy: A narrative review.
More than half of pregnant women are usually affected by odontogenic pain affects. Pain often accompanies periapical or pulp infections and increases the risks to pregnant patients and their fetuses. The American Dental Association, in partnership with the American College of Obstetricians and Gynecologists, has offered a strong declaration reaffirming the significance of suitable and timely oral health care as an indispensable constituent of a healthy pregnancy. However, there is lack of knowledge about the use of antibiotics in endodontic treatment. Therefore, the present study would review the researches done in this area and tries to provide comprehensive and complete information about the use of antibiotics in endodontic treatment during pregnancy. Based on the results, it can be said that using antibiotics during pregnancy are allowed, and they can be used normally and safely by pregnant women.


Endovascular Techniques and Peripheral Vascular Surgery.
Endovascular is an increasingly popular term that describes the use of catheter-based instruments to diagnose and treat vascular disease. Implicit in this terminology is its association with techniques that are less invasive to the patient than traditional surgical techniques. Endovascular techniques began in 1963 with the advent of the Fogarty arterial embolectomy catheter for removal of clotted blood from the peripheral arterial circulation. Shortly thereafter, radiologist Charles Dotter introduced the concept of arterial dilatation which was popularised a decade later by cardiologist Andreas Gruntzig with the use of a non-dispensible plastic balloon catheter. During the next two decades, endovascular techniques proliferated in the growing fields of interventional cardiology and interventional radiology, yet were embraced more slowly by the surgical community.


Discovery of O-GlcNAc-modified proteins in published large-scale proteome data.
The attachment of N-acetylglucosamine to serine or threonine residues (O-GlcNAc) is a post-translational modification on nuclear and cytoplasmic proteins with emerging roles in numerous cellular processes, such as signal transduction, transcription, and translation. It is further presumed that O-GlcNAc can exhibit a site-specific, dynamic and possibly functional interplay with phosphorylation. O-GlcNAc proteins are commonly identified by tandem mass spectrometry following some form of biochemical enrichment. In the present study, we assessed if, and to which extent, O-GlcNAc-modified proteins can be discovered from existing large-scale proteome data sets. To this end, we conceived a straightforward O-GlcNAc identification strategy based on our recently developed Oscore software that automatically analyzes tandem mass spectra for the presence and intensity of O-GlcNAc diagnostic fragment ions. Using the Oscore, we discovered hundreds of O-GlcNAc peptides not initially identified in these studies, and most of which have not been described before. Merely re-searching this data extended the number of known O-GlcNAc proteins by almost 100 suggesting that this modification exists even more widely than previously anticipated and the modification is often sufficiently abundant to be detected without enrichment. However, a comparison of O-GlcNAc and phospho-identifications from the very same data indicates that the O-GlcNAc modification is considerably less abundant than phosphorylation. The discovery of numerous doubly modified peptides (i.e. peptides with one or multiple O-GlcNAc or phosphate moieties), suggests that O-GlcNAc and phosphorylation are not necessarily mutually exclusive, but can occur simultaneously at adjacent sites.


Dendrimer-functionalized single-wall carbon nanotubes: synthesis, characterization, and photoinduced electron transfer.
We describe the synthesis and characterization of a series of single-wall carbon nanotubes (SWNTs) functionalized with polyamidoamine dendrimers. Importantly, the dendrimers are linked directly to the SWNT surface using a divergent methodology. This approach allows the number of functional groups on the nanotubes to be increased without provoking significant damage to the conjugated pi-system of the SWNTs. Several tetraphenylporphyrin moieties can be linked to the periphery of the dendrimers, and the photophysical properties of the resulting nanoconjugates have been investigated with a series of steady-state and time-resolved spectroscopy. The fluorescence kinetics provide evidence for two transient decays, one very short-lived (i.e., 0.04 +/- 0.01 ns) and one long-lived (i.e., 8.6 +/- 1.2 ns). A possible explanation is that some porphyrin units do not interact with the nanotubes, thus exhibiting a fluorescence lifetime similar to that of the free porphyrin. Complementary transient absorption measurements not only corroborate the fast decay of the photoexcited tetraphenylporphyrin but also confirm that intraconjugate charge separation evolves from the excited porphyrin to the SWNTs.


[Isolated liver perfusion in advanced metastases of colorectal cancers].
A special cannulation system was developed in order to completely isolate the liver in an extracorporeal circuit. Isolated hyperthermic liver perfusion at 40 degrees C with an average dosage of 1000 mg 5-FU was performed in 32 patients with liver metastases (29 colorectal carcinomas, 2 carcinoids, 1 primary hepatoma). 12 patients who had an overall 45% tumor invasion of the entire liver-volume as measured in CT-scan were treated exclusively by isolated liver perfusion. In that group median survival was 8 months and death occurred in the presence of extrahepatic metastases. Better results are achieved with isolated liver perfusion followed by intraarterial short-time infusions (Mitomycin C/5-FU) via an Implantofix catheter. Median actual survival in this group is 12 months, the longest follow-up period is 23 months.


Anti-inflammatory effect of kamebakaurin in in vivo animal models.
We have identified kamebakaurin as an inhibitor of NF-KB and elucidated its molecular mechanism as a specific inhibitor in the DNA-binding activity of the p50 subunit of NF-KB. Here, we describe its anti-inflammatory activity in in vitro and in vivo models. Kamebakaurin dose-dependently inhibited not only the expression of inflammatory NF-KB target genes such as iNOS,COX-2, and TNF-x, but also the production of PGE2 and TNF-a in LPS-stimulated RAW264.7 cells. Moreover, in an air pouch model of inflammation, it suppressed the recruitment of neutrophils,production of TNF-a as well as PGE2 in the pouch exudates induced by carrageenan. In addition, kamebakaurin dose-dependently suppressed the inflammation in an adjuvant arthritis model. Oral administration of 20 mg/kg kamebakaurin resulted in the 75% decrease of paw volume. Taken together, kamebakaurin, a specific inhibitor of DNA-binding activity of the p50 subunit, is a valuable candidate for the intervention in NF-KB-dependent pathological conditions such as inflammation.


Canadian biotechnology start-ups, 1991-1997: the role of incumbents' patents and strategic alliances in controlling competition.
Fligstein (1996) contends that organizations act to exploit the institutional context in which they are embedded so as to stabilize the competition they face. Drawing on Fligstein's theoretical analysis, we conceptualize incumbent biotechnology firms' patent-ing and alliance-building activities as attempts to stabilize and control potential competition and analyze how these activities shape rates of founding in the Canadian biotechnology industry. We find that increases in the level and concentration of incumbents' patenting discourage founding, particularly in human application sectors of the industry where development and approval processes are more costly and time consuming. Incumbents' horizontal alliances depress start-ups; vertical alliances stimulate start-ups. Our findings highlight how technology appropriation and strategic alliances structure the competitive dynamics and evolution of high-technology, knowledge-intensive industries.


[Cerebral amyloid angiopathy].
The most usual form of cerebral amyloid angiopathy is due to deposition of B protein on vessel walls. This senile angiopathy is often, but inconstantly, associated with Alzheimer's disease, and rarely causes intracerebral hemorrhage, which is typically lobar and recurrent, occurring in elderly normotensive patients with ou without dementia. There is probably no cause-effect relationship between senile cerebral amyloid angiopathy and Alzheimer's disease, which may occur independently and seems to represent two modalities of cerebral amyloidosis. Other forms of cerebral amyloid angiopathy are exceptional: hereditary cerebral hemorrhages with amyloidosis differ from each another in type of fibrillar protein (cystatine-C, variant of B protein, transthyretine).


Insulin binding and degradation by kidney cell membranes of streptozotocin-diabetic rats.
The interaction of insulin with purified rat kidney cell membranes was studied with the use of 125I-insulin. The membranes showed high insulin-degrading activity which was dependent on temperature, time and membrane concentration. Specific binding of insulin was demonstrated in the presence of 0.3 mM bacitracin and was time- and temperature-dependent. 125I-insulin was displaced by native insulin, AI-B29 dodecoyl insulin and proinsulin in proportion to their relative bioactivity. Kidney membranes isolated from streptozotocin-diabetic rats bound more insulin per mg of membrane protein (approx. 65%) than did membranes of control animals. Scatchard analysis indicated that this increase in binding was due to an increased binding capacity rather than an increased affinity for insulin. Injection of diabetic rats with insulin resulted in a decrease of insulin binding when compared with the untreated diabetic animals. Diabetes also resulted in altered kinetics of insulin degradation.


Solid phase synthesis of functionalised SAM-forming alkanethiol-oligoethyleneglycols.
We present an efficient solid phase synthesis methodology that provides easy access to a range of functionalised long-chain alkanethiol-oligoethyleneglycols that form well-defined self-assembled monolayers on gold and are compatible with pre- or post-assembly conjugation of (bio)molecules. We demonstrate the versatility of our synthetic route by synthesising LCAT-OEGs with a range of functional moieties, including peptides, electro-active redox groups, chemical handles for post-assembly conjugation of (bio)molecules, and demonstrate the application of our LCAT-OEG monolayers in immunosensing, where they show good biocompatibility with minimal biofouling.


Salicylic Acid Induces Changes in Mango Fruit that Affect Oviposition Behavior and Development of the Oriental Fruit Fly, Bactrocera dorsalis.
The Oriental fruit fly, Bactrocera dorsalis (Hendel) is an important quarantine pest around the globe. Although measures for its control are implemented worldwide through IPM and male annihilation, there is little effect on their population. Hence, there is a need for new strategies to control this minacious pest. A strategy that has received negligible attention is the induction of 'natural plant defenses' by phytohormones. In this study, we investigated the effect of salicylic acid (SA) treatment of mango fruit (cv. Totapuri) on oviposition and larval development of B. dorsalis. In oviposition choice assays, gravid females laid significantly less eggs in SA treated compared to untreated fruit. Headspace volatiles collected from SA treated fruit were less attractive to gravid females compared to volatiles from untreated fruit. GC-MS analysis of the headspace volatiles from SA treated and untreated fruit showed noticeable changes in their chemical compositions. Cis-ocimene and 3-carene (attractants to B. dorsalis) were reduced in the headspace volatiles of treated fruit. Further, reduced pupae formation and adult emergence was observed in treated fruit compared to control. Increased phenol and flavonoid content was recorded in treated fruit. We also observed differential expression of anti-oxidative enzymes namely catalase (CAT), polyphenoloxidase (PPO) and peroxidase (POD). In summary, the results indicate that SA treatment reduced oviposition, larval development and adult emergence of B. dorsalis and suggest a role of SA in enhancing mango tolerance to B. dorsalis.


Ergot, the "jerks," and revivals.
Epidemics of epilepsy, a form of mass hysteria, were known in Eastern and Western cultures in the 17th and 18th centuries. A unique situation in the United States during the 19th centurey was the frontier religious movement, the setting in which the "jerks" occurred. The "falling exercise," "dancing exercise," "barking exercise," "laughing exercise," and the "running exercise" centered around the excitement involved in the religious revival. During some exercises, people saw "visions," and exhibited bizarre behavior and sudden jerking motions. During the summers of 1801-1803 on the Kentucky frontier, some pioneers who attended the religious revival camp meetings had convulsions, hallucinations, tremors, jerks, compulsive dancing and "epileptic trances." Although these have been assumed to be psychological in origin, the epidemiology of the symptoms may correlate with the diagnosis of ergotism. Those affected were usually children and young adults. Symptoms of ergotism include giddiness, fatigue, depression, formications, muscle twitching, tonic spasms, convulsions, delirium, and loss of speech.


Study of mercury resistance and Fourier transform infrared spectroscopy-based metabolic profiling of a potent Bacillus tropicus strain from forest soil.
Mercury (Hg) is a highly toxic heavy metal and Hg-resistant indigenous bacterial isolates may offer a green and cost-effective bioremediation strategy to counter Hg contamination. In this study, a potent Hg-resistant bacterium was isolated from the forest soil of a bird sanctuary. Identification using matrix-assisted laser desorption ionization-time of flight mass spectrometry depicted the isolate as a strain of Bacillus tropicus, validated by morphological, biochemical, and molecular studies. The isolate demonstrated biological Hg removal efficiency and capacity of 50.67% and 19.76 mg g-1 , respectively. The plasmid borne resistance determinant, merA, encoding mercuric reductase, was detected in the bacterium endowing it with effective Hg volatilization and resistance capability. A Fourier-transform infrared spectroscopic comparative metabolic profiling revealed the involvement of various functional groups like -COOH, -CH2 , -OH, PO4 - and so on, resulting in differential spectral patterns of the bacterium both in control and Hg-exposed situations. A temporal variance in metabolic signature was also observed during the early and mid-log phase of growth in the presence of Hg. The bacterium described in this study is the first indigenous Hg-resistant strain isolated from the Uttar Dinajpur region, which could be further explored and exploited as a potent bioresource for Hg remediation.


[The 1188 A/C ILI2B gene polymorphism in patients with multiple sclerosis and in healthy subjects of Tomsk region].
Multiple sclerosis (MS) is a multifactorial and polygenic disorder of the central nervous system, its development being under strong influence of T-helpers type I which produce anti-inflammation cytokines. Interleukin 12 (IL12) plays a key role in such polarization of the immune response. Genotyping for polymorphism of the IL12B gene in the 3'-untranslated region, coding for the p40(IL12B) subunit, has been carried out in 62 patients with MS and 129 healthy controls. The C/C genotype frequency was twice higher in patients as compared to the controls (33.9% and 17.4%, respectively). The allele C in patients was associated with shorter duration of the first remission (p = 0.028) which was 1.79 +/- 0.28 in those with the C allele and 3.27 +/- 0.68 in other patients. Mean rate of relapses per year was also higher (p = 0.079) in patients with the C allele (0.96 +/- 0.11) comparing with the A allele (0.72 +/- 0.11). During the treatment with copaxone, a trend towards increasing of the time before the first relapse was observed in patients with the C allele. An analysis of immunologic indices revealed that they changed in opposite directions depending on the gene variant. The C-allele is suggested to have relation both to liability to MS and to its pathogenesis.


Immunophenotyping and Cell Sorting of Human MKs from Human Primary Sources or Differentiated In Vitro from Hematopoietic Progenitors.
Megakaryocyte (MK) differentiation encompasses a number of endomitotic cycles that result in a highly polyploid (reaching even >64N) and extremely large cell (40-60 µm). As opposed to the fast-increasing knowledge in megakaryopoiesis at the cell biology and molecular level, the characterization of megakaryopoiesis by flow cytometry is limited to the identification of mature MKs using lineage-specific surface markers, while earlier MK differentiation stages remain unexplored. Here, we present an immunophenotyping strategy that allows the identification of successive MK differentiation stages, with increasing ploidy status, in human primary sources or in vitro cultures with a panel integrating MK specific and non-specific surface markers. Despite its size and fragility, MKs can be immunophenotyped using the above-mentioned panel and enriched by fluorescence-activated cell sorting under specific conditions of pressure and nozzle diameter. This approach facilitates multi-Omics studies, with the aim to better understand the complexity of megakaryopoiesis and platelet production in humans. A better characterization of megakaryopoiesis may pose fundamental in the diagnosis or prognosis of lineage-related pathologies and malignancy.


Bacteriomimetic poly-γ-glutamic acid surface coating for hemocompatibility and safety of nanomaterials.
Poly-γ-glutamic acid (PGA), a major component of the bacterial capsule, is known to confer hydrophilicity to bacterial surfaces and protect bacteria from interactions with blood cells. We tested whether applying a bacteriomimetic surface coating of PGA modulates interactions of nanomaterials with blood cells or affects their safety and photothermal antitumor efficacy. Amphiphilic PGA (APGA), prepared by grafting phenylalanine residues to PGA, was used to anchor PGA to reduced graphene oxide (rGO) nanosheets, a model of hydrophobic nanomaterials. Surface coating of rGO with bacterial capsule-like APGA yielded APGA-tethered rGO nanosheets (ArGO). ArGO nanosheets remained stable in serum over 4 weeks, whereas rGO in plain form precipitated in serum within 5 minutes. Moreover, ArGO did not interact with blood cells, whereas rGO in plain form or as a physical mixture with PGA formed aggregates with blood cells. Mice administered ArGO at a dose of 50 mg/kg showed 100% survival and no hepatic or renal toxicity. No mice survived exposure at the same dose of rGO or a PGA/rGO mixture. Following intravenous administration, ArGO showed a greater distribution to tumors and prolonged tumor retention compared with other nanosheet formulations. Irradiation with near-infrared light completely ablated tumors in mice treated with ArGO. Our results indicate that a bacteriomimetic surface modification of nanomaterials with bacterial capsule-like APGA improves the stability in blood, biocompatibility, tumor distribution, and photothermal antitumor efficacy of rGO. Although APGA was used here to coat the surfaces of rGO, it could be applicable to coat surfaces of other hydrophobic nanomaterials.


CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers.
CD73, a cell surface 5'nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.


The leader meter--a feedback survey.
A survey rates leadership behavior at all levels. The confidential feedback survey accomplishes three things: (1) it gives valuable feedback about leadership skills; (2) it gives employees a voice or a chance to be heard; and (3) it encourages teambuilding.


Electronic and Structural Factors Controlling the Spin Orientations of Magnetic Ions.
Magnetic ions M in discrete molecules and extended solids form MLn complexes with their first-coordinate ligand atoms L. The spin moment of M in a complex MLn prefers a certain direction in coordinate space because of spin-orbit coupling (SOC). In this minireview, we examine the structural and electronic factors governing the preferred spin orientations. Elaborate experimental measurements and/or sophisticated computational efforts are required to find the preferred spin orientations of magnetic ions, largely because the energy scale of SOC is very small. The latter is also the very reason why one can readily predict the preferred spin orientation of M by analyzing the SOC-induced highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) interactions of the MLn complexes in terms of qualitative perturbation theory. The strength of this HOMO-LUMO interaction depends on the spin orientation, which is governed by the selection rules based on the minimum |ΔLz| value (i.e., the minimum difference in the magnetic quantum numbers) between the HOMO and LUMO. With the local z axis of MLn chosen as its n-fold rotational axis, the preferred spin orientation is parallel to the z axis (∥z) when |ΔLz| = 0 but perpendicular to the z axis (⊥z) when |ΔLz| = 1.


The Use of TADs in the Mandibular Arch to Prevent Proclination of the Lower Incisors during the Use of the Mini Scope Herbst Appliance.
Class II malocclusions are the most frequent within the Italian population. Normally, these malocclusions are caused by a reduction in a mandibular component whose functional stimulus is still very much cause for debate. The negative effect of all types of Class II functional appliances is in the proclination of the lower incisors, which, in subjects whose incisors are already labially inclined, must be checked at all times to avoid serious consequences to these elements. In this case study, a girl aged 14 years and 5 months presented with Class II malocclusion, 2nd division with a convex profile and a visibly retruded chin. The lower incisors presented a marked proclination (-1/Go-Gn ini = 107.7°) in a brachyfacial patient. To avoid further inclination of the lower incisors a Herbst appliance was mounted in two separate sittings. The first part of the appliance including the tubes was mounted to the upper jaw allowing the vestibularisation of the upper incisors in order to increase the overjet. Once this was obtained the lower part of the appliance was mounted together with the telescopic arms associated with two temporary anchorage devices (TADs) in positions 36-37 and 46-47, and an anterior section 33-43 with distal loop to which two double metallic ligatures were anchored at the TADs to contrast the negative effect of the appliance. At the end of the first functional phase, the treatment was refined using MBK fixed therapy to finish the case. The orthodontic therapy led to a visible improvement of the profile and the achievement of a first-class dental-skeletal result on both sides. From the cephalometric evaluation carried out immediately after the Herbst appliance treatment at time T1 and at the end of the orthodontic therapy T2 it was possible to verify a slight increase in the inclination of the lower incisors (-1/Go-Gn fin = 108°). In conclusion, it can be said that the use of the skeletal anchorage avoided, in this case, the proclination effect in the lower incisors due to the use of a Herbst appliance.


Singapore Defibrillation Guidelines 2016.
The most common initial rhythm in a sudden cardiac arrest is ventricular fibrillation or pulseless ventricular tachycardia. This is potentially treatable with defibrillation, especially if provided early. However, any delay in defibrillation will result in a decline in survival. Defibrillation requires coordination with the cardiopulmonary resuscitation component for effective resuscitation. These two components, which form the key links in the chain of survival, have to be brought to the cardiac victim in a timely fashion. An effective chain of survival is needed in both the institution and community settings.


Rapid Proliferation and Differentiation of a Subset of Circulating IgM Memory B Cells to a CpG/Cytokine Stimulus In Vitro.
Circulating human IgM expressing memory B cells have been incompletely characterized. Here, we compared the phenotype and in vitro functional response (capacity to proliferate and differentiate to antibody secreting cells) in response to CpG and a cytokine cocktail (IL-2, IL-6, and IL-10) of sorted naïve B cells, IgM memory B cells and isotype-switched circulating memory B cells. Compared to naïve B cells, IgM memory B cells had lower integrated mean fluorescence intensity (iMFI) of BAFF-R, CD38, CD73, and IL-21R, but higher iMFI of CD95, CD11c, TLR9, PD-1, and CD122. Compared to switched memory B cells, IgM memory B cells had higher iMFI of BAFF-R, PD-1, IL-21R, TLR9, and CD122, but lower iMFI of CD38, CD95, and CD73. Four days after receiving the CpG/cytokine cocktail, higher frequencies of IgM than switched memory B cells-and these in turn greater than naïve cells-proliferated and differentiated to antibody secreting cells. At this time point, a small percentage (median of 7.6%) of stimulated IgM memory B cells changed isotype to IgG. Thus, among the heterogeneous population of human circulating IgM memory B cells a subset is capable of a rapid functional response to a CpG/cytokine stimulus in vitro.


Facilitating care transitions for older adults.
Successful transitions between care settings can reduce the chance of complications for older adults with complex health conditions. Ensuring good transitions involves not only executing a well-thought-out medical plan but also referring patients to support services in the community and attending to the needs and well-being of their caregivers. This article describes why these factors are so important and how physicians can use Minnesota resources to improve care transitions.


Neural correlates of the belief-bias effect in syllogistic reasoning: an event-related potential study.
This study investigated electrophysiological correlates of belief-bias effects in syllogistic reasoning. Event-related brain potentials were recorded for minor premises with which participants were required to draw a logic conclusion during three conditions: the inhibitory belief condition (IBC, the belief is inhibitory to the logical task), the facilitatory belief condition (FBC, the belief is facilitatory to the logical task), and the baseline condition. The results demonstrated a more positive event-related potential deflection during IBC and FBC conditions than during the noninference baseline condition in both the 300-500 and the 1000-1600 ms time windows. Moreover, IBC elicited a more positive event-related potential deflection (P500) than did FBC across central-frontal cortical regions during the 300-600 ms interval. Therefore, this study observed a clear belief-bias effect, and the enhanced P500 activity during IBC, which relates to the belief bias that obstructs normal inferences, most likely reflects an inhibition to beliefs during later relation integration stage.


Neonatal enterovirus infections: emphasis on risk factors of severe and fatal infections.
Neonatal enterovirus infections have diverse manifestations, from asymptomatic to fatal. An understanding of the risk factors associated with severe cases might help to reduce enterovirus-related morbidity and mortality. From July 1989 through June 1998, neonates with virus culture-confirmed nonpolio enterovirus infection at Chang Gung Children's Hospital were enrolled in the study and divided into three groups: nonspecific febrile illness; aseptic meningitis; and hepatic necrosis with coagulopathy (HNC). Demographic factors, clinical manifestations, laboratory data and outcome were analyzed to reveal factors associated with clinical severity and fatality. There were 146 cases including 43 neonates with nonspecific febrile illness, 61 with aseptic meningitis and 42 with HNC. By multiple logistic regression analysis, the most significant factors associated with HNC were prematurity, maternal history of illness, earlier age of onset (< or =7 days), higher white blood cell count (WBC > or =15 000/mm3) and lower hemoglobin (< or =10.7 g/dl). In 10 (24%) of 42 cases, HNC was fatal. In comparison with nonfatal cases of HNC, fatal cases had higher WBC, lower hemoglobin, higher bilirubin and higher incidence of concurrent myocarditis. Multivariate analysis showed the most significant factors associated with fatality from HNC to be total bilirubin >14.3 mg/dl (adjusted odds ratio, 29.1; 95% confidence interval, 2.5 to 355.5; P = 0.007) and concurrent myocarditis (adjusted odds ratio, 13.7; 95% confidence interval, 1.1 to 177.2; P = 0.04). Intravenous immunoglobulin did not correlate with clinical outcomes in cases with HNC. Prematurity, maternal history of illness, earlier age of onset, higher WBC and lower hemoglobin are significant factors associated with HNC; higher total bilirubin and concurrent myocarditis were most significantly associated with fatality from HNC.


Application of femtosecond laser microsurgery in assisted reproductive technologies for preimplantation embryo tagging.
Femtosecond laser pulses were applied for precise alphanumeric code engraving on the zona pellucida (ZP) of mouse zygotes for individual embryo marking and their identification. The optimal range of laser pulse energies required for safe ZP microsurgery has been determined. ZP was marked with codes in three different planes to simplify the process of embryo identification. No decrease in developmental rates and no morphological changes of embryos post laser-assisted engraving have been observed. ZP thickness of embryos post laser-assisted code engraving has been shown to differ significantly from that of control group embryos at the hatching stage. Due to moderate ZP thinning as compared to its initial width at 0.5 dpc (days post coitum), readability of the code degrades slightly and it still remains recognizable even at hatching stage. Our results demonstrate that application of femtosecond laser radiation could be an effective approach for noninvasive direct embryo tagging, enabling embryo identification for the whole period of preimplantation development.


Conventional total hip arthroplasty for degenerative joint disease in patients between the ages of forty and sixty years.
We analyzed the records of 103 conventional hip arthroplasties in seventy-five active patients who were between the ages of forty and sixty years. After five to ten years of follow-up, an excellent or good clinical result was evident in 90 per cent. The radiographic appearance of the cement-bone interface of the acetabular component was stable in those hips, and no progressive acetabular radiolucency was found in 80 per cent of the hips. Of twenty hips with a complete acetabular radiolucency (Grade III or IV), only three had a secondary revision operation, two in conjunction with a fracture of the stem of the prosthesis and one for migration (Grade IV). Eight additional hips showed migration. Seventy per cent of the femoral components were well fixed, without radiographic evidence of loosening. A fracture of the femoral stem occurred in eight hips, all of which had a revision operation. One revision operation was done for loosening of the femoral stem. Seven femoral stems showed either shift or subsidence. An isolated radiolucency in the superolateral zone was present in four hips and an isolated lucency in other zones, measuring one millimeter or less, was present in ten hips. Thus, radiographic evidence of loosening, including the hips with a fractured stem, was present in 29.9 per cent. One additional revision, making ten in all, was done for symptomatic acetabular loosening. Based on this study, we concluded that conventional hip arthroplasty is a highly successful treatment in active patients between forty and sixty years old who have osteoarthritis of the hip.


Effect of Kiwifruit on Bone Resorption in Ovariectomized Mice.
Kiwifruit is a good source of dietary components and has beneficial effects for health. In this study, we investigated the effects of two types of kiwifruit, green kiwifruit (GRK) and gold kiwifruit (GOK), on bone metabolism in ovariectomized (OVX) mice. Seven-week-old female Balb/c-strain mice were divided into four groups: sham-operated (sham) group, OVX group, and OVX mice that were fed a GRK-supplemented diet or GOK-supplemented diet. Freeze-dried GRK and GOK were prepared and added in the diet at a concentration of 3 g/100 g. After 9 wk, the mice were sacrificed, and the serum, uterus, and femurs were obtained. Final body weight did not differ significantly among the four groups. Compared to the sham group, uterine weight was significantly lower and serum C-terminal telopeptide of type I collagen (CTx) levels and receptor activator of NF-κB ligand (RANKL) mRNA expression of the whole femur were significantly higher in the OVX group. Compared to the OVX group, GRK, but not GOK, reduced serum CTx concentrations and RANKL mRNA expression of the whole femur without changes in uterine weight. These results suggest that the GRK inhibited bone resorption, which might be due to a decrease in RANKL mRNA expression in OVX mice.


Influence of excessive dietary protein intake during late gestation on drylot beef cow performance and progeny growth, carcass characteristics, and plasma glucose and insulin concentrations.
Spring-calving cows ( = 49) were used to investigate the effects of excessive prepartum dietary protein intake on late gestation cow performance as well as subsequent progeny growth, carcass characteristics, and plasma glucose and insulin concentrations. Treatments were formulated to be isocaloric and provide 100% (REQ) or 129% (HP) of CP requirement. Treatments were limit-fed 78 ± 12 d prepartum to calving. All cows were fed a common diet postpartum. Cow BW and BCS were recorded at initiation of treatments and within 48 h post-calving. Milk production was estimated via the weigh-suckle-weigh technique 69 ± 11 d postpartum. Calf BW was measured at birth and at weaning (121 ± 11 d of age). Progeny ( = 42) were weaned as a group and placed into a feedlot and fed a common finishing diet. Glucose and insulin concentrations were analyzed on a subset of progeny (12 per treatment) 90, 120, 150, 180, 210, and 240 min post-feeding, 2 d before slaughter (342 ± 11 d of age). Treatment had no effect ( ≥ 0.22) on cow BW, BCS, milk production, and subsequent reproduction or progeny preweaning growth. Progeny finishing growth and marbling scores were not affected ( ≥ 0.24) by treatment, yet 12th rib fat thickness ( < 0.01), KPH ( = 0.04), and YG ( = 0.01) were greater for progeny born to HP dams. Progeny born to HP dams had decreased ( ≤ 0.01) glucose and insulin concentrations, and insulin to glucose ratios, indicating greater insulin sensitivity. Although feeding cows 129% of CP requirement during late gestation did not affect cow performance or progeny preweaning or finishing period growth; carcass adiposity was increased by maternal treatment.


Acute effect of sulphur dioxide from a power plant on pulmonary function of children, Thailand.
Epidemiological studies have shown reversible declines of lung function in response to air pollution, but research on the independent effect of short-term exposure to ambient sulphur dioxide (SO2) on pulmonary function is limited. This study evaluated the association of short-term exposure to increased ambient SO2 and daily pulmonary function changes among children with and without asthma. The associations of daily exposure to SO2 and particulate matter 10 microm in diameter (PM10) with pulmonary function were examined in 175 asthmatic and non-asthmatic children aged 6-14 years who resided near a coal-fired power plant in Thailand. Each child performed daily pulmonary function tests during the 61-day study period. General linear mixed models were used to estimate the association of air pollution and pulmonary function controlling for time, temperature, co-pollutants, and autocorrelation. In the asthmatic children, a daily increase in SO2 was associated with negligible declines in pulmonary function, but a small negative association was found between PM10 and pulmonary function. A 10-microg/m(3) increment was associated with changes in the highest forced vital capacity (FVC) (-6.3 ml, 95% CI: -9.8, -2.8), forced expiratory volume at 1 second (FEV(1)) (-6.0 ml, 95% CI: -9.2, 2.7), peak expiratory flow rate (PEFR) (-18.9 ml.sec(-1), 95% CI: -28.5, -9.3) and forced expiratory flow 25 to 75% of the FVC (FEF(25-75%)) (-3.7 ml.sec(-1), 95% CI: -10.9, 3.5). No consistent associations between air pollution and pulmonary function were found for non-asthmatic children. Declines in pulmonary function among asthmatic children were associated with increases in particulate air pollution, rather than with increases in SO2.


Comment on "transition to turbulence in a shear flow".
In this Comment two main issues are addressed that are pertinent to the interpretation of the transition to turbulence for shear type flows on the basis of transient chaos: the fractal character associated with this transition and the precision needed for a reliable numerical modeling. The analysis is based on a simplified model of 19 degrees of freedom for Couette flow, proposed some years ago by Eckhardt and Mersmann. We conclude that the landscape of lifetimes cannot be fractal, and that a very high numerical accuracy is needed to obtain sound results.


Vault predicting after implantable collamer lens implantation using random forest network based on different features in ultrasound biomicroscopy images.
To analyze ultrasound biomicroscopy (UBM) images using random forest network to find new features to make predictions about vault after implantable collamer lens (ICL) implantation. A total of 450 UBM images were collected from the Lixiang Eye Hospital to provide the patient's preoperative parameters as well as the vault of the ICL after implantation. The vault was set as the prediction target, and the input elements were mainly ciliary sulcus shape parameters, which included 6 angular parameters, 2 area parameters, and 2 parameters, distance between ciliary sulci, and anterior chamber height. A random forest regression model was applied to predict the vault, with the number of base estimators (n_estimators) of 2000, the maximum tree depth (max_depth) of 17, the number of tree features (max_features) of Auto, and the random state (random_state) of 40.0. Among the parameters selected in this study, the distance between ciliary sulci had a greater importance proportion, reaching 52% before parameter optimization is performed, and other features had less influence, with an importance proportion of about 5%. The importance of the distance between the ciliary sulci increased to 53% after parameter optimization, and the importance of angle 3 and area 1 increased to 5% and 8% respectively, while the importance of the other parameters remained unchanged, and the distance between the ciliary sulci was considered the most important feature. Other features, although they accounted for a relatively small proportion, also had an impact on the vault prediction. After parameter optimization, the best prediction results were obtained, with a predicted mean value of 763.688 µm and an actual mean value of 776.9304 µm. The R2 was 0.4456 and the root mean square error was 201.5166. A study based on UBM images using random forest network can be performed for prediction of the vault after ICL implantation and can provide some reference for ICL size selection.


Development and implementation of a relationship-focused outpatient multifamily program for adolescent anorexia nervosa.
Multifamily therapy (MFT) for adolescent eating disorders (ED) is anchored in systemic theory and family therapy, but two conceptual and practical paths have emerged from this common framework. The first one, called ED-focused MFT, is centered on behavioral change and weight gain in the early stages of treatment, while the second, known as relationship-focused MFT, is less directly focused on symptom improvement and more on family changes. Compared to ED-focused MFT, validation of more relationship-focused MFT models has been lagging behind although they are frequently implemented and practiced in Europe. The purpose of this article is to give more visibility to existing relationship-focused MFT models by presenting an integrative, yet predominantly family-oriented MFT program developed for adolescent anorexia nervosa (AN) (12 to 18 years) on the ED unit of a large pediatric hospital in France. After presenting the history and development of this relationship-focused MFT program, including the challenges it encountered and its evaluation, we describe its rationale and objectives, then outline its course and content, giving illustrations of techniques and activities for each of the five phases of the program. Finally, we review the current status of this model, its advantages and limitations, and provide a critical appraisal of existing evidence and recommended future research directions.


Changes in subcortical white matter in the unaffected hemisphere following unilateral spontaneous intracerebral hemorrhage: a tract-based spatial statistics study.
We investigated changes in the subcortical white matter in the unaffected hemisphere in patients with unilateral intracerebral hemorrhage (ICH) by applying tract-based spatial statistics (TBSS) analysis. Twenty-four patients with ICH and 17 healthy control subjects were recruited for this study. Diffusion tensor imaging (DTI) data were obtained at least four weeks after ICH onset. TBSS analysis was performed using fractional anisotropy (FA) DTI data. We calculated mean FA values across the tract skeleton and within 27 regions of interest (ROIs) based on the observed intersections between the FA skeleton and the probabilistic Johns Hopkins University white matter atlases. The FA values of 27 ROIs in the unaffected hemisphere in the patient group were significantly lower than those of the control group (p < 0.05). In terms of a causal relationship between possible confounding factors (sex, age, lateralization [right], lesion volume), a negative correlation coefficient was observed in five ROIs (the tapetum, sagittal stratum, column and body of the fornix, posterior corona radiate, inferior cerebellar peduncle, superior cerebellar peduncle) in the regression analysis (p < 0.05). In the patient group, moderate negative correlations were detected between ICH volume and the FA values of two ROIs: the sagittal stratum, r = -0.479, p < 0.05; the tapetum, r = -0.414, p < 0.05. We detected extensive neural injury of the subcortical white matter in the unaffected hemisphere in patients with unilateral ICH. In addition, injury severities of neural structures located around the mid-sagittal line or periventricular areas were correlated with ICH volume.


Saving the rainforest through health care: medicine as conservation in Borneo.
This article gives an overview of rainforest conservation as it relates to human health and describes the context, design, and implementation of the Kelay Conservation Health Program (KCHP). The KCHP is a health program for indigenous people living in a critical area of orangutan rainforest habitat in Indonesian Borneo also developed to aid conservation efforts there. Program design included consideration of both health and conservation goals, participatory planning in collaboration with the government health system, a focus on community managed health, capacity building, and adaptive management. After two years the program had, at relatively low cost, already had positive impacts on both human health (e.g., child immunization rates) and conservation (e.g., local forest protection measures, attitudes of villagers and government officials towards the implementing conservation agency).


[Expression of T-lymphocyte antigens by serum B lymphocytes in rheumatoid polyarthritis].
Molecules recognised by the monoclonal antibodies Leu 1 - OKT 1 - Mid 5 (CD5 molecules) were originally shown on human T cells and are equivalent to Lyt-1 molecules in the mouse. These surface molecules are detectable on some human B cells, but are weakly expressed. We have therefore tested the effects of the tumour-promoter, phorbol myristic acetate (PMA) on expression of these molecules on B cells. Sheep red blood cell rosette-depleted lymphoid organ or blood cells from 8 controls and 10 rheumatoid arthritis (RA) patients were examined fresh and cultured with PMA for 48 hours and the cells stained with Leu 1 or Mid 5 by indirect immunofluorescence. Cells were analysed by UV microscopy or flow cytometry. More RA blood B cells were positive for Leu 1 than normals before culture. Following incubation with PMA, the percentage of positive cells increased in all cell populations (1-49% in RA patients and 5-26% in controls). There was no difference in the expression of Leu 1 on Kappa--or lambda--positive cells before and after culture in PMA. Leu 1 positive cells were under-represented in Epstein-Barr virus-driven cell lines.


Effect of alizarin red S on rat blood and its calcium content.
The vital staining mechanism of alizarin red S (ARS) was investigated. The total calcium content of rat blood was determined after intraperitoneal and intracardial administration of acidic, neutralized and calcium-supplemented ARS. The administration of ARS causes, irrespective of chemical state, a remarkable decrease in blood volume and a significant decrease in the serum/blood ratio. The total calcium content of rat serum was noticeably increased, more in the case of intracardial than in the case of intraperitoneal administration. The calcium values determined in this work were the sums of free and bound calcium. The increase in calcium content even in those cases where ARS was administered without calcium indicates a physiological ability to keep the concentration of free calcium constant in the blood. The highest calcium values were found when calcium-supplemented ARS was administrated. The physiological activity, however, seems to be higher with acidic ARS, which also contributed to the vital staining effect on rat skull. The best staining with least inconvenience was achieved using neutralized ARS for in vivo staining.


A GENERAL MODEL FOR KIN SELECTION.
Inclusive fitness theory is central to our understanding of the evolution of social behavior. By showing the importance of genetic transmission through nondescendent relatives, it helps to explain the evolution of reproductively altruistic behaviors, such as those observed in the social insects. Inclusive fitness thinking is quantified by Hamilton's rule, but Hamilton's rule has often been criticized for being inexact or insufficiently general. Here I show how adopting a genic perspective yields a very general version that remains pleasingly simple and transparent.


Human papillomavirus infection among human immunodeficiency virus-infected women in Maharashtra, India.
Frequency and distribution of HPV types in HIV-infected women with and without cervical neoplasia and their determinants have not been widely studied in India. We report and discuss HPV prevalence and type distribution in HIV-infected women. HPV genotyping was done using cervical samples from 1109 HIV-infected women in a cross-sectional study. Any HPV was detected in 44.8% and high-risk ones in 41.0% women. Frequency of single and multiple high-risk infections were 26.7% and 14.3%, respectively. Frequencies of high-risk HPV infections in women with and without cervical neoplasia were 73.5% and 37.6%, respectively. HPV16 was the most common genotype, present in 11.5%, and 58.5% of women with cervical intraepithelial neoplasia (CIN) 2 and 3. Other most common high-risk HPV types in CIN 2-3 lesions were HPV 31 (22.6%); 56 (13.2%); 18 and 68a (11.3%) and 33, 35 and 51 (9.4%); and 70 (7.5%). Women under 30 or over 44 years, no abortions, and women with diagnosis of HIV infection within the last 5 years were at high risk of multiple oncogenic HPV infection. We observed a very high frequency of high-risk HPV and multiple infections in HIV-infected women.


Biodentine™ material characteristics and clinical applications: a 3 year literature review and update.
Biodentine™ has frequently been acknowledged in the literature as a promising material and serves as an important representative of tricalcium silicate based cements used in dentistry. To provide an update on the physical and biological properties of Biodentine™ and to compare these properties with those of other tricalcium silicate cements namely, different variants of mineral trioxide aggregate (MTA) such as ProRoot MTA, MTA Angelus, Micro Mega MTA (MM-MTA), Retro MTA, Ortho MTA, MTA Plus, GCMTA, MTA HP and calcium enriched mixture (CEM), Endosequence and Bioaggregate™. A comprehensive literature search for publications from November 20, 2013 to November 20, 2016 was performed by two independent reviewers on Medline (PubMed), Embase, Web of Science, CENTRAL (Cochrane), SIGLE, SciELO, Scopus, Lilacs and clinicaltrials.gov. Electronic and hand search was carried out to identify randomised control trials (RCTs), case control studies, case series, case reports, as well as in vitro and animal studies published in the English language. The enhanced physical and biologic properties of Biodentine™ could be attributed to the presence of finer particle size, use of zirconium oxide as radiopacifier, purity of tricalcium silicate, absence of dicalcium silicate, and the addition of calcium chloride and hydrosoluble polymer. Furthermore, as Biodentine™ overcomes the major drawbacks of MTA it has great potential to revolutionise the different treatment modalities in paediatric dentistry and endodontics especially after traumatic injuries. Nevertheless, high quality long-term clinical studies are required to facilitate definitive conclusions.


[Acute injury to the gastric mucosa by acetylsalicylic acid. A comparative endoscopic study in man with oral prostaglandin analogs, omeprazole and ranitidine].
The deleterious effects of acetylsalicylic acid (ASA) on gastric mucosa have been well documented in experimental and clinical studies. With a direct endoscopic assay system we evaluated in healthy volunteers whether pretreatment with prostaglandin analogues (misoprostol, rioprostil), omeprazole and ranitidine prevented ASA-induced gastric mucosal injuries. Ranitidine (2 X 150 mg/d) in large antisecretory doses almost completely abolished these changes (p less than 0.05). By contrast, misoprostol (4 X 50 micrograms/d and 4 X 200 micrograms/d), rioprostil (3 X 100 micrograms/d), omeprazole (5 mg and 10 mg/d) as well as ranitidine in non-antisecretory doses (2 X 25 mg/d) did not reduce gastric mucosal injury after single-dose ASA administration. The results of this trial indicate that socalled cytoprotective doses of prostaglandins, omeprazole and ranitidine in contrast to animal findings are not effective in preventing acute ASA-induced mucosal damage.


Short term orthodontics.
Short-term orthodontics is a growing area of clinical care delivery. Many practitioners who have not experienced specialist orthodontic education are involved in the provision of that care. Limited orthodontic treatment can provide a level of tooth movement but the essential challenge arises from the patient's expectations and their acceptance of the possible outcomes. As with all techniques, short-term orthodontics is not a panacea of care and the patient's motivation and the identification of specific cases which might benefit, is essential. Providers clearly use the technique in different ways and this paper highlights areas of caution.


Dose-effects of aorta-infused clenbuterol on spinal cord ischemia-reperfusion injury in rabbits.
The β2 adrenergic receptor (β2AR) plays an important role in ischemia-reperfusion (I/R) injury in various organs. Recently, a selective β2AR agonist clenbuterol was suggested to protect against cerebral I/R injury. This study was designed to investigate changes of β2ARs after spinal cord I/R injury and dose-effects of aorta-infused clenbuterol on spinal cord I/R injury in rabbits. Spinal cord ischemia was induced in New Zealand white rabbits by infrarenal abdominal aortic occlusion with a balloon catheter for 30 minutes except the sham group. During occlusion, nothing (I/R group), normal saline (NS group) or clenbuterol at different doses of 0.005, 0.01, 0.05, 0.1, 0.5, or 1 mg/kg (C0.005, C0.01, C0.05, C0.1, C0.5, and C1 groups) was infused into the occluded aortic segments. The hemodynamic data, blood glucose and serum electrolytes were measured during experimental period. Neurological function was assessed according to the modified Tarlov scales until 48 hours after reperfusion. After that, the lumbar spinal cord was harvested for β2AR immunohistochemistry and histopathologic evaluation in the anterior horns. The β2AR expression in the anterior horns of the spinal cord was significantly higher in the I/R group than in the sham group. Tarlov scores and the number of viable α-motor neurons were higher in C0.01-C0.5 groups than in the NS group, C0.005 and C1 groups and were highest in the C0.1 group. Hypotension and hyperglycemia were found in the C1 group. β2ARs in the anterior horn were upregulated after spinal cord I/R injury. Aortic-infused clenbuterol (0.01-0.5 mg/kg) can attenuate spinal cord I/R injury dose-dependently during the ischemic period. The Optimal dosage was 0.1 mg/kg. Activation of β2AR could be a new therapeutic strategy for the treatment of spinal cord I/R injury.


Effect of Cavitation Bubble Collapse on the Modification of Solids: Crystallization Aspects.
This review examines the concepts how cavitation bubble collapse affects crystalline structure, the crystallization of newly formed structures, and recrystallization. Although this subject can be discussed in a broad sense across the area of metastable crystallization, our main focus is discussing specific examples of the inorganic solids: metal, intermetallics, metal oxides, and silicon. First, the temperature up to which ultrasound heats solids is discussed. Cavitation-induced changes in the crystal size of intermetallic phases in binary AlNi (50 wt % of Ni) alloys allow an estimation of local temperatures on surfaces and in bulk material. The interplay between atomic solid-state diffusion and recrystallization during bubble collapses in heterogeneous systems is revealed. Furthermore, cavitation triggered red/ox processes at solid/liquid interfaces and their influence on recrystallization are discussed for copper aluminum nanocomposites, zinc, titanium, magnesium-based materials, and silicon. Cavitation-driven highly nonequilibrium conditions can affect the thermodynamics and kinetics of mesoscopic phase formation in heterogeneous systems and in many cases boost the macroscopic performance of composite materials, notably in catalytic alloy and photocatalytic semiconductor oxide properties, corrosion resistance, nanostructured surface biocompatibility, and optical properties.


Cutaneous mast cell tumor with epitheliotropism in 3 dogs.
Epitheliotropism is an important diagnostic feature of cutaneous epitheliotropic lymphoma and canine cutaneous histiocytoma; however, although noted in certain feline mastocytic diseases, it has not been considered a feature of canine cutaneous mast cell tumor. In this study, 3 canine cutaneous mast cell tumors had epitheliotropic invasion of neoplastic mast cells into the epidermis and follicular epithelium. This unusual histologic finding was characterized by infiltrates of individual and clusters of neoplastic mast cells in the stratum basale and stratum spinosum. The mast cell origin of these cells was documented by demonstration of metachromasia with Giemsa stain and positive immunoreactivity to KIT protein. On the basis of these findings, mast cell tumors should be included in the differential diagnosis for canine cutaneous round cell neoplasms that infiltrate the epidermis.


Targeting Oxidative Stress as a Therapeutic Approach for Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by an abnormal reepithelialisation, an excessive tissue remodelling and a progressive fibrosis within the alveolar wall that are not due to infection or cancer. Oxidative stress has been proposed as a key molecular process in pulmonary fibrosis development and different components of the redox system are altered in the cellular actors participating in lung fibrosis. To this respect, several activators of the antioxidant machinery and inhibitors of the oxidant species and pathways have been assayed in preclinical in vitro and in vivo models and in different clinical trials. This review discusses the role of oxidative stress in the development and progression of IPF and its underlying mechanisms as well as the evidence of oxidative stress in human IPF. Finally, we analyze the mechanism of action, the efficacy and the current status of different drugs developed to inhibit the oxidative stress as anti-fibrotic therapy in IPF.


Investigating the relationship between socially-assigned ethnicity, racial discrimination and health advantage in New Zealand.
While evidence of the contribution of racial discrimination to ethnic health disparities has increased significantly, there has been less research examining relationships between ascribed racial/ethnic categories and health. It has been hypothesized that in racially-stratified societies being assigned as belonging to the dominant racial/ethnic group may be associated with health advantage. This study aimed to investigate associations between socially-assigned ethnicity, self-identified ethnicity, and health, and to consider the role of self-reported experience of racial discrimination in any relationships between socially-assigned ethnicity and health. The study used data from the 2006/07 New Zealand Health Survey (n = 12,488), a nationally representative cross-sectional survey of adults 15 years and over. Racial discrimination was measured as reported individual-level experiences across five domains. Health outcome measures examined were self-reported general health and psychological distress. The study identified varying levels of agreement between participants' self-identified and socially-assigned ethnicities. Individuals who reported both self-identifying and being socially-assigned as always belonging to the dominant European grouping tended to have more socioeconomic advantage and experience less racial discrimination. This group also had the highest odds of reporting optimal self-rated health and lower mean levels of psychological distress. These differences were attenuated in models adjusting for socioeconomic measures and individual-level racial discrimination. The results suggest health advantage accrues to individuals who self-identify and are socially-assigned as belonging to the dominant European ethnic grouping in New Zealand, operating in part through socioeconomic advantage and lower exposure to individual-level racial discrimination. This is consistent with the broader evidence of the negative impacts of racism on health and ethnic inequalities that result from the inequitable distribution of health determinants, the harm and chronic stress linked to experiences of racial discrimination, and via the processes and consequences of racialization at a societal level.


Three-dimensional reconstruction and NURBS-based structured meshing of coronary arteries from the conventional X-ray angiography projection images.
Despite its two-dimensional nature, X-ray angiography (XRA) has served as the gold standard imaging technique in the interventional cardiology for over five decades. Accordingly, demands for tools that could increase efficiency of the XRA procedure for the quantitative analysis of coronary arteries (CA) are constantly increasing. The aim of this study was to propose a novel procedure for three-dimensional modeling of CA from uncalibrated XRA projections. A comprehensive mathematical model of the image formation was developed and used with a robust genetic algorithm optimizer to determine the calibration parameters across XRA views. The frames correspondences between XRA acquisitions were found using a partial-matching approach. Using the same matching method, an efficient procedure for vessel centerline reconstruction was developed. Finally, the problem of meshing complex CA trees was simplified to independent reconstruction and meshing of connected branches using the proposed nonuniform rational B-spline (NURBS)-based method. Because it enables structured quadrilateral and hexahedral meshing, our method is suitable for the subsequent computational modelling of CA physiology (i.e. coronary blood flow, fractional flow reverse, virtual stenting and plaque progression). Extensive validations using digital, physical, and clinical datasets showed competitive performances and potential for further application on a wider scale.


Sedative use and misuse in the United States.
To determine the prevalence and correlates associated with sedative use and misuse in the general population. Data were drawn from the National Comobidity Survey (n = 8098), a representative sample of adults in the community. Multivariate logistic regression analyses were used to identify correlates of sedative use, non-prescription use and self-perceived dependence. The life-time prevalence of self-perceived sedative dependence was 0.5%, 7.1% reported non-prescribed sedative use and 17.0% had been prescribed sedatives and denied misuse. Individuals who used sedatives without a prescription were more likely to be male (OR = 0.61 (0.44, 0.86)), have lower income (OR = 0.71 (0.54, 0.94)), more education (OR = 1.51 (1.17, 1.96)), major depression (OR = 1.47 (1.04, 2.08)), agoraphobia (OR = 1.59 (1.09, 2.32)), ASPD (OR = 5.29 (3.42, 8.20)) and suicide ideation (OR = 1.91 (1.23, 2.94)), compared with those who did not use sedatives. Individuals with self-perceived dependence on sedatives were older (OR = 1.05 (1.02, 1.08)), had less education (OR = 0.2 (0.1, 0.7)) and were more likely to have a parent who abused prescription medications (OR = 4.3 (1.03, 18.03)), compared with those without sedative dependence. Almost one in 10 adults report misuse of sedatives in their lifetime. Sedative use and misuse are associated with high levels of psychopathology and suicide risk, and show a specific association with parental abuse of prescription medications in the general population. Future work to understand more effectively the nature of these associations may ultimately lead to improved effectiveness of preventive interventions.


Alpha-adrenoceptors and benign prostatic hyperplasia: basic principles for treatment with alpha-adrenoceptor antagonists.
The selective blockade of alpha1-adrenoceptors (ARs) is now a well-accepted and widely used treatment for patients presenting with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and bladder outlet obstruction. The sites of action of the currently used alpha1-AR antagonists when relieving LUTS have not yet been established, but it seems clear that effects on prostatic as well as non-prostatic tissues are important. Alpha1-ARs in the bladder, urethra, and vas deferens, on ganglia and nerve terminals, and in the central nervous system (CNS) may all influence LUTS and the clinical effects of alpha1-AR antagonists. The relevance of alpha1-AR subtype selectivity for the clinical usefulness of existing drug therapy has still not been clarified, but it cannot be dismissed that blockading both alpha1A- and alpha1D-ARs is necessary for optimal clinical effect. Despite the above uncertainties, there seems to be a consensus that clinically available alpha1-AR antagonists provide a safe, effective and generally well-tolerated therapy for patients with LUTS.


Micellear Gold Nanoparticles as Delivery Vehicles for Dual Tyrosine Kinase Inhibitor ZD6474 for Metastatic Breast Cancer Treatment.
The therapeutic index of poorly water-soluble drugs is often hampered due to poor pharmacokinetics, reduced blood retention, and lack of effective drug concentrations in the tumor region. In order to overcome these issues, drugs are often delivered by use of delivery vehicles to provide an enhanced therapeutic index. Gold nanoparticles synthesized in micellar networks of amphiphilic block copolymer (AuNM) provide an efficient nanocarrier for tissue- and site-specific drug delivery owing to their low cytotoxicity and immunogenicity. AuNM is formed by exploiting the properties of both inorganic Au material and an amphiphilic polymer of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG). We further functionalized AuNM with the FDA-approved dual tyrosine kinase inhibitor ZD6474 and studied the physicochemical properties of the conjugate ZD6474-AuNM. Both AuNM and ZD6474-AuNM, with a diameter of ∼70 nm, were very stable at physiological pH. Conversely, at an acidic pH of 5.2, a slow sustained-release profile of ZD6474 was evident from AuNM, which could provide a method of facilitating release of the drug in an acidic tumor environment. In vitro, in triple-negative breast cancer cells, ZD6474-AuNM inhibited tumor cell proliferation, migration, and invasion and induced apoptosis. There was no detectable lysis of red blood cells observed when they were treated with AuNM and ZD6474-AuNM, confirming hemocompatibility. To reinforce the possibility of AuNM serving as a delivery vehicle, AuNM was conjugated with the IR680 dye for tracking, and this conjugate was systemically delivered in female nude mice bearing MDA-MB-231 human breast cancer xenografts. Fluorescence signal was retained in the tumor region in a temporal manner as compared to other organs, indicating passive retention of AuNM in the tumor locale. Moreover, delivery of ZD6474-AuNM in nude mice bearing MDA-MB-231 xenografts led to decreased tumor size as compared to the control group. The promising safety, targeting, and therapeutic results of systemic delivery of ZD6474 by AuNM provide an attractive alternative method for treating patients with metastatic breast cancer.


14-Deoxy-11,12-didehydroandrographolide attenuates excessive inflammatory responses and protects mice lethally challenged with highly pathogenic A(H5N1) influenza viruses.
Traditional Chinese medicine (TCM) has been an excellent treasury for centuries' accumulation of clinical experiences, which deserves to be tapped for potential drugs and improved using modern scientific methods. 14-Deoxy-11,12-didehydroandrographolide (DAP), a major component of an important TCM named Andrographis paniculata, with non-toxic concentration of 1000 mg/kg/day, effectively reduced the mortality and weight loss of mice lethally challenged with A/chicken/Hubei/327/2004 (H5N1) or A/PR/8/34 (H1N1) influenza A viruses (IAV) when initiated at 4 h before infection, or A/duck/Hubei/XN/2007 (H5N1) when initiated at 4 h or 48 h before infection, or 4 h post-infection (pi). DAP (1000 or 500 mg/kg/day) also significantly diminished lung virus titres of infected mice when initiated at 4 h or 48 h before infection, or 4 h pi. In the infection of A/duck/Hubei/XN/2007 (H5N1), DAP (1000 mg/kg/day) treatment initiated at 48 h before infection gained the best efficacy that virus titres in lungs of mice in log10TCID50/mL reduced from 2.61 ± 0.14 on 3 days post-infection (dpi), 2.98 ± 0.17 on 5 dpi, 3.54 ± 0.19 on 7 dpi to 1.46 ± 0.14 on 3 dpi, 1.86 ± 0.18 on 5 dpi, 2.03 ± 0.21 on 7 dpi. Moreover, DAP obviously alleviated lung histopathology and also strongly inhibited proinflammatory cytokines/chemokines expression. The mRNA levels of TNF-α, IL-1β, IL-6, CCL-2/MCP-1, IFN-α, IFN-β, IFN-γ, MIP-1α, MIP-1β in lungs of A/duck/Hubei/XN/2007 (H5N1)-infected mice and serum protein expression of TNF-α, IL-1β, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10 in mice infected with all the three strains of IAV were all significantly reduced by DAP. Results demonstrated that DAP could restrain both the host intense inflammatory responses and high viral load, which were considered to contribute to the pathogenesis of H5N1 virus and should be controlled together in a clinical setting. Considering the anti-inflammatory and anti-IAV activities of DAP, DAP may be a promising active component obtained from A. paniculata, which can be further investigated as a useful constitute of curative strategies in the future against IAV, the H5N1 strains in particular.


Zebrafish Models in Therapeutic Research of Cardiac Conduction Disease.
Malfunction in the cardiac conduction system (CCS) due to congenital anomalies or diseases can cause cardiac conduction disease (CCD), which results in disturbances in cardiac rhythm, leading to syncope and even sudden cardiac death. Insights into development of the CCS components, including pacemaker cardiomyocytes (CMs), atrioventricular node (AVN) and the ventricular conduction system (VCS), can shed light on the pathological and molecular mechanisms underlying CCD, provide approaches for generating human pluripotent stem cell (hPSC)-derived CCS cells, and thus improve therapeutic treatment for such a potentially life-threatening disorder of the heart. However, the cellular and molecular mechanisms controlling CCS development remain elusive. The zebrafish has become a valuable vertebrate model to investigate early development of CCS components because of its unique features such as external fertilization, embryonic optical transparency and the ability to survive even with severe cardiovascular defects during development. In this review, we highlight how the zebrafish has been utilized to dissect the cellular and molecular mechanisms of CCS development, and how the evolutionarily conserved developmental mechanisms discovered in zebrafish could be applied to directing the creation of hPSC-derived CCS cells, therefore providing potential therapeutic strategies that may contribute to better treatment for CCD patients.


The Role of AMPK in the Regulation of Skeletal Muscle Size, Hypertrophy, and Regeneration.
AMPK (5'-adenosine monophosphate-activated protein kinase) is heavily involved in skeletal muscle metabolic control through its regulation of many downstream targets. Because of their effects on anabolic and catabolic cellular processes, AMPK plays an important role in the control of skeletal muscle development and growth. In this review, the effects of AMPK signaling, and those of its upstream activator, liver kinase B1 (LKB1), on skeletal muscle growth and atrophy are reviewed. The effect of AMPK activity on satellite cell-mediated muscle growth and regeneration after injury is also reviewed. Together, the current data indicate that AMPK does play an important role in regulating muscle mass and regeneration, with AMPKα1 playing a prominent role in stimulating anabolism and in regulating satellite cell dynamics during regeneration, and AMPKα2 playing a potentially more important role in regulating muscle degradation during atrophy.


Irisin Is Target of Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor-Mediated Signaling in Skeletal Muscle Cells.
Irisin is a hormone-like myokine produced in abundance by skeletal muscle (SkM) in response to exercise. This myokine, identical in humans and mice, is involved in many signaling pathways related to metabolic processes. Despite much evidence on the regulators of irisin and the relevance of sphingolipids for SkM cell biology, the contribution of these latter bioactive lipids to the modulation of the myokine in SkM is missing. In particular, we have examined the potential involvement in irisin formation/release of sphingosine-1-phosphate (S1P), an interesting bioactive molecule able to act as an intracellular lipid mediator as well as a ligand of specific G-protein-coupled receptors (S1PR). We demonstrate the existence of distinct intracellular pools of S1P able to affect the expression of the irisin precursor FNDC. In addition, we establish the crucial role of the S1P/S1PR axis in irisin formation/release as well as the autocrine/paracrine effects of irisin on myoblast proliferation and myogenic differentiation. Altogether, these findings provide the first evidence for a functional crosstalk between the S1P/S1PR axis and irisin signaling, which may open new windows for potential therapeutic treatment of SkM dysfunctions.


Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis.
The 2016 revision of the World Health Organization (WHO) classification of myeloproliferative neoplasms defines 2 stages of primary myelofibrosis (PMF): prefibrotic/early (pre-PMF) and overt fibrotic (overt PMF) phase. In this work, we studied the clinical and molecular features of patients belonging to these categories of PMF. The diagnosis of 661 PMF patients with a bone marrow biopsy at presentation was revised according to modern criteria; clinical information and annotation of somatic mutations in both driver and selected nondriver myeloid genes were available for all patients. Compared with pre-PMF, overt PMF was enriched in patients with anemia, thrombocytopenia, leukopenia, higher blast count, symptoms, large splenomegaly, and unfavorable karyotype. The different types of driver mutations were similarly distributed between the 2 categories, whereas selected mutations comprising the high mutation risk (HMR) category (any mutations in ASXL1, SRSF2, IDH1/2, EZH2) were more represented in overt PMF. More patients with overt PMF were in higher International Prognostic Scoring System risk categories at diagnosis, and the frequency increased during follow-up, suggesting greater propensity to disease progression compared with pre-PMF. Median survival was significantly shortened in overt PMF (7.2 vs 17.6 years), with triple negativity for driver mutations and presence of HMR mutations representing independent predictors of unfavorable outcome. The findings of this "real-life" study indicate that adherence to 2016 WHO criteria allows for identification of 2 distinct categories of patients with PMF where increased grades of fibrosis are associated with more pronounced disease manifestations, adverse mutation profile, and worse outcome, overall suggesting they might represent a phenotypic continuum.


Slim and obese children's perceptions of physical activities.
Two studies of children's perceptions of physical activities were carried out. The first examined the views of 600 ten-year-olds drawn from seven regions of Australia; the second examined the views of 528 ten-year-olds from South Australia. Both studies revealed consistent differences between the perceptions of obese and slim children. Obese children evaluated endurance activities more negatively and flexibility-coordination activities more positively than slim children. These differences were highly stable between samples and over time.


Azaacene containing iridium(III) phosphors: elaboration of the π-conjugation effect and application in highly efficient solution-processed near-infrared OLEDs.
Azaacenes have attracted wide research interest due to their tremendous potential in organic electronics. However, near-infrared (NIR) light-emitting iridium(III) phosphors bearing azaacene derivatives are rarely investigated. In this contribution, two solution-processable heteroleptic iridium(III) complexes, namely DBPzIr and PPzIr, are rationally designed and synthesized, and they contain a rigid phenanthrene- or pyrene-fused diazaacene core and two peripheral groups of 4-tert-butyl-phenyl attached at the 12,13-positions in the core, respectively. The effects of the diazaacene core and appending groups on the optoelectronic properties of both complexes are systematically investigated. A dramatically red-shifted NIR emission peak at 789 nm with a photoluminescence quantum yield (PLQY) of 14% is observed in PPzIr compared with the 746 nm emission with a PLQY of 40% in DBPzIr. Taking advantage of their photophysical properties, the solution-processed device doped with DBPzIr achieves a maximum external quantum efficiency (EQEmax) of 8.00% with a radiance of 54 866 mW Sr-1 m-2 at 716 nm and the device doped with PPzIr exhibits a significantly red-shifted emission at 772 nm with an EQEmax of 3.53%. The achieved device performance is among the best values in the reported NIR-OLEDs based on iridium(III) complexes via a solution process at the same color gamut. Our study indicates that the reasonable collocation of the rigid diazaacene chelating core and flexible peripheral groups in the iridium(III) complex is of great significance in designing highly efficient NIR emitters.


[Clinical and radiological results of distal radius fractures].
We report retrospective analysis of results of conservative and operative methods of distal radial fractures, which was carried out to control our treatment methods. Three hundred and ninety-three patients were treated from 1. 7. 1991 to 1. 7. 1992, 361 (91.9%) were followed up to 14 months with average age of 60.1 years (16 to 92 years). Three hundred and twenty-seven patients (90.6%) were treated by conservative methods, 9 (2.5%) by percutaneous pinning, 21 (5.8%) by transfixation through bases of metacarpal bones and 4 (1.1%) by ventral supporting plates. Clinical examination showed 69.6% good, 24.9% fair and 5.5% poor results. Radiological results according to AO-scheme were compared with clinical results, and 70% clinical results correlated with radiological results. Our results show that comminuted and displaced intraarticular fractures AO-classification C 2, C 3 are indications of transfixation and A 3 and some exceptional cases of C 1 are indications of percutaneous pinning.


Axillary lymph node dissection for intraductal breast carcinoma--is it indicated?
One hundred patients with intraductal breast carcinoma (DCIS) were treated with either mastectomy (49 patients) or radiation therapy (51 patients). All patients underwent axillary lymph node dissection (average number of nodes removed, 16) as part of their treatment. No patient had any positive axillary lymph nodes. There has been one recurrence in each treatment group (median follow-up, 27 months) and no deaths. Intraductal breast carcinoma has little potential for metastasis to axillary lymph nodes.


Liposomal nanoparticle armed with bivalent bispecific single-domain antibodies, novel weapon in HER2 positive cancerous cell lines targeting.
Breast cancer is the leading cause of mortality among all cancers. HER2, human epidermal growth factor receptors type 2, a receptor tyrosine kinase that induces interminable cell proliferation, is overexpressed in 20-25 percent of breast cancers. In spite of significant progress in nanomedicine in the past decade, being subjected to genetic drift that hides many paramount epitopes has rendered targeting HER2 as a big challenge. In the present study, we developed monovalent and bivalent monospecific along with bivalent bispecific VHH targeting different epitopes on HER2, and showed that bivalent bispecific VHH has the highest affinity among other tested modalities. Then we covalently coupled VHHs to the fluorescent labeled liposomal nanoparticle to produce targeted liposomes. Based on flow cytometry results, bivalent bispecific VHH targeted liposomes showed the highest fluorescent intensity, on HER2 breast cancer cells. Liposomes conjugated to bivalent monospecific VHH exhibited enhanced affinity toward HER2 positive cell lines compared to monovalent targeted liposomes, with bivalent bispecific liposomes appearing as the most robust probe.


Edge electron density profiles and fluctuations measured by two-dimensional beam emission spectroscopy in the KSTAR.
Beam emission spectroscopy (BES) system in Korea Superconducting Tokamak Advanced Research (KSTAR) has recently been upgraded. The background intensity was reduced from 30% to 2% by suppressing the stray lights. This allows acquisition of the relative electron density profiles on the plasma edge without background subtraction from the beam power modulation signals. The KSTAR BES system has its spatial resolution of 1 cm, the temporal resolution of 2 MHz, and a total 32 channel (8 radial × 4 poloidal) avalanche photo diode array. Most measurements were done on the plasma edge, r/a ∼ 0.9, with 8 cm radial measurement width that covers the pedestal range. High speed density profile measurements reveal temporal behaviors of fast transient events, such as the precursors of edge localized modes and the transitions between confinement modes. Low background level also allows analysis of the edge density fluctuation patterns with reduced background fluctuations. Propagation of the density structures can be investigated by comparing the phase delays between the spatially distributed channels.