The Impact of Generativity Awareness on Mid- to Old-Age Smokers in China.
Smoking remains a serious health threat to many mid- to old-age Chinese people. Many smoking interventions have been implemented in public areas, but smoking occurring in a private setting, such as at home, has largely been neglected. Generativity is based on evaluating the worth of one's life experience that can be passed on to others. This study evaluated whether generativity awareness can have an impact on smoking reduction. Five hundred and eight Chinese smokers were recruited and demonstrated their strong awareness of generativity, specifically general generativity (e.g., moral ethics), health-related generativity (e.g., living a healthy life), and smoke-free family generativity. The study showed support for a three-dimensional model for generativity, namely general, health, and smoke-free generativity. The three types of generativity varied in their effects on behavioral intention to reduce smoking and to encourage younger family members not to smoke. Family communication patterns also influenced behavioral intention to reduce smoking and to encourage younger family members not to smoke. Theoretical and practical implications are discussed.


Content Validation of the Organizational Climate for Research Integrity (OCRI) Survey.
THE PURPOSE OF THIS STUDY WAS TO develop and establish content validity of an instrument designed to measure the organizational climate for research integrity in academic health centers. Twenty-seven research integrity scholars and administrators evaluated 64 survey items for relevance and clarity, as well as overall comprehensiveness of the constructs that are measured (organizational inputs, structures, processes and outcomes). Both quantitative and qualitative methods were used, particularly content validity indices (CVI) and analyses of respondents' comments. The content validity index for the overall survey was initially high (CVI = .83) and improved (CVI = .90) when 17 marginal-to-poor items were removed. This study resulted in the Organizational Climate for Research Integrity (OCRI) survey, a 43-item fixed-response survey with established content validity.


Partial sensory denervation of the upper respiratory tract on allergen- and histamine-induced bronchoconstriction.
The influence of partial denervation of the upper part of the respiratory tract on histamine- and antigen-induced bronchoconstriction was investigated in a series of 12 boxer dogs. To achieve this purpose, the superior laryngeal, hypoglossal and glossopharyngeal nerves were sectioned. The prophylactic effect of unilateral transection of these nerves on antigen-induced bronchoconstriction originating in the upper respiratory tract could be demonstrated.


Fullerene superlattices containing charge transfer complexes for an improved nonlinear optical performance.
To improve the nonlinear optical (NLO) properties of fullerene C60, chemical modifications are normally needed to construct a donor-π-acceptor (D-π-A) system, which requires tedious and time-consuming synthesis procedures. In addition, the conjugated structure of C60 will inevitably be destroyed, which is disadvantageous for other applications. Here, we use solvent-based nanoarchitectonics to obtain highly ordered, three-dimensional (3D) C60 supramolecular structures. For this purpose, a liquid-liquid interfacial precipitation (LLIP) method was employed using quinoline as the good solvent. Hollow polyhedra (HPH) and multilayer flowers (MFs) were obtained when methanol and ethanol were selected as the poor solvents, respectively. While quinoline failed to enter the HPH, it was found to be successfully intercalated with the MFs, which induced a transition of the C60 organization from a pristine face-centered-cubic (fcc) phase to a hexagonal close packed (hcp) lattice. When embedded in a poly(methyl methacrylate) (PMMA) matrix, the HPH and MFs both show reverse saturable absorption (RSA) and optical limiting (OL) properties. The MFs-based film showed a third-order nonlinear absorption coefficient (β) of 1.25 × 105 cm·GW-1 and an optical limiting threshold (Fol) of 0.00625 J·cm-2. Comparatively, the HPH-based film exhibited a lower β value of 9.80 × 104 cm GW-1 and a higher Fol value of 0.00834 J cm-2. The better NLO performance of the MFs was mainly ascribed to the formation of the charge transfer complexes between quinoline and C60, proven by UV-vis and electrochemical measurements. The fine tuning of the NLO properties of C60 without chemical modification provides new opportunities for C60 to be applied in nonlinear optics.


The Breast-Cancer Education and Wellness (BE Well) Intervention: Congregants' Intended Participation, Actual Participation, and Perceived Health Outcomes.
Objective. To evaluate a health leader-focused church-based breast cancer prevention intervention in relation to congregants' intended participation, congregants' actual participation, and perceived health outcomes at both individual and church levels using socio-ecological and theory of planned behavior frameworks. Method. Participants for the study were African American adults (n = 52) from six churches in a North Florida county involved in implementing the 9-month, three-phase intervention. Using a pre/post without comparison group design, data were collected via self-administered surveys and analyzed using qualitative and quantitative (descriptive, analysis of variance, linear regression) procedures. Results. There was general alignment between congregants' intended and actual participation when analyzed by content, especially in the areas of food and nutrition and health education. Regarding the number of intended versus actual activities, there was a significant, negative change in physical activity, a slight decline in health education activities, but a slight increase in food and nutrition activities. No significant relationships were found between extent of participation and the individual health outcomes (health ratings, health status), but significant relationships were found between extent of participation and church health outcomes (perceived role of church in improving health, p < .001; perceived role of the pastor in improving health, p < .001). Conclusions. The findings demonstrate that (1) congregants may follow through and participate in church-based health activities in which they express interest and that are made available and (2) the extent of their participation may be influenced by the perceived role of both the church and the pastor in improving their health.


Bilateral sequential non-arteritic optic neuropathy post-COVID-19.
Corona virus disease 2019 (COVID-19) has been documented to have a spectrum of neuro-ophthalmic manifestations. However, bilateral non-arteritic anterior ischemic optic neuropathy (NAION) post-COVID-19 has not been reported in the literature. We studied the case of a 45-year-old male who presented to our outpatient department (OPD) with bilateral blurring of vision following an episode of COVID-19, 1 month back. Examination and investigations were conclusive of a bilateral NAION. The patient was given a trial of oral steroids. However, the vision loss could not be recovered. Thus, through this case report, we would like to highlight the importance of a close follow-up of patients following COVID-19 infection to detect any sequelae.


Pooled assembly of marine metagenomic datasets: enriching annotation through chimerism.
Despite advances in high-throughput sequencing, marine metagenomic samples remain largely opaque. A typical sample contains billions of microbial organisms from thousands of genomes and quadrillions of DNA base pairs. Its derived metagenomic dataset underrepresents this complexity by orders of magnitude because of the sparseness and shortness of sequencing reads. Read shortness and sequencing errors pose a major challenge to accurate species and functional annotation. This includes distinguishing known from novel species. Often the majority of reads cannot be annotated and thus cannot help our interpretation of the sample. Here, we demonstrate quantitatively how careful assembly of marine metagenomic reads within, but also across, datasets can alleviate this problem. For 10 simulated datasets, each with species complexity modeled on a real counterpart, chimerism remained within the same species for most contigs (97%). For 42 real pyrosequencing ('454') datasets, assembly increased the proportion of annotated reads, and even more so when datasets were pooled, by on average 1.6% (max 6.6%) for species, 9.0% (max 28.7%) for Pfam protein domains and 9.4% (max 22.9%) for PANTHER gene families. Our results outline exciting prospects for data sharing in the metagenomics community. While chimeric sequences should be avoided in other areas of metagenomics (e.g. biodiversity analyses), conservative pooled assembly is advantageous for annotation specificity and sensitivity. Intriguingly, our experiment also found potential prospects for (low-cost) discovery of new species in 'old' data. email@example.com Supplementary data are available at Bioinformatics online.


Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development.
Dramatic changes in chromatin structure and histone modification occur during oocyte growth, as well as a global cessation of transcription. The role of histone modifications in these processes is poorly understood. We report the effect of conditionally deleting Hdac1 and Hdac2 on oocyte development. Deleting either gene has little or no effect on oocyte development, whereas deleting both genes results in follicle development arrest at the secondary follicle stage. This developmental arrest is accompanied by substantial perturbation of the transcriptome and a global reduction in transcription even though histone acetylation is markedly increased. There is no apparent change in histone repressive marks, but there is a pronounced decrease in histone H3K4 methylation, an activating mark. The decrease in H3K4 methylation is likely a result of increased expression of Kdm5b because RNAi-mediated targeting of Kdm5b in double-mutant oocytes results in an increase in H3K4 methylation. An increase in TRP53 acetylation also occurs in mutant oocytes and may contribute to the observed increased incidence of apoptosis. Taken together, these results suggest seminal roles of acetylation of histone and nonhistone proteins in oocyte development.


Comprehensive Quantitative and Calibration-Free Evaluation of Hyperpolarized Xenon-Host Interaction by Multiparametric NMR.
The probing of microscopic environments by hyperpolarized xenon NMR has spurred investigations in supramolecular chemistry as well as important biosensing and molecular imaging applications. While xenon exchange with host structures at micromolar concentrations and below can be readily detected, a quantitative analysis is limited, requiring complementary experimentation by different methodologies and thus lacking completeness and compromising the validity and comparability of numerical results. Here, a new NMR measurement and data analysis approach is introduced for the comprehensive characterization of the host-xenon binding dynamics. The application of chemical exchange saturation transfer of hyperpolarized 129Xe under parametric modulation of the saturation RF amplitude and xenon gas saturation of the solution enables a delineation of exchange mechanisms and, through modeling, a numerical estimation of the various reaction rate constants (and thus magnetization exchange rate constants), the xenon affinity, and the total host molecule concentration. Only the numerical xenon solubility is additionally required for input, a quantity that has a low impact on the measurement uncertainty and is derivable from metrological data collections. Signal calibration by a reference material may thus be avoided, qualifying the method as calibration-free. For demonstration a xenon exchange with the host cucurbit[6]uril at low concentration is investigated, with the numerical results being validated by standard quantitative NMR data obtained at high concentration. The readiness to evaluate xenon exchange for the one sample at hand and in a single experimental attempt by the proposed method may allow comprehensive quantitative studies in supramolecular chemistry, biomacromolecular structure and dynamics, and sensing.


LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common human cancers. Long non-coding RNA (lncRNA) has been demonstrated to play an important role in regulating tumor development. The current study aims to explore the specific role of LINC00520 during HCC progression. The present study identified that LINC00520 was upregulated in HCC tissues and indicated poor patient survival. Overexpression of LINC00520 promoted HCC cell proliferation, migration and invasion, while LINC00520 downregulation led to the opposite effects. Besides, LINC00520 knockdown was found to inhibit tumor growth in vivo. Furthermore, LINC00520 acted as a sponge of miR-4516 to regulate SRY-related high mobility group box 5 (SOX5). In addition, the inhibition of miR-4516 partly reversed the inhibitory effect of LINC00520 silencing on HCC cell proliferation, migration and invasion. In conclusion, the inhibition of LINC00520 suppressed HCC cell proliferation, migration and invasion through mediating miR-4516/SOX5 axis. Therefore, our study provides a basis for the development of treatment strategies for HCC.


[A novel nanoparticle in treatment of staphylococcus aureus and pseudomonas aeruginosa biofilms].
Objective:To investigate CPC-nanoparticles of low concentrations in treatment of staphylococcus aureus and pseudomonas aeruginosa biofilms in vitro. Method: We established specific biofilms of staphylococcus aureus ATCC 25923 and pseudomonas aeruginosa ATCC 15692, and prepared CPC-nanoparticles and CPC micelle solutions of low concentrations(0.010%, 0.025% and 0.050%). AlamarBlue was used to test the viability of both planktonic staphylococcus aureus and pseudomonas aeruginosa and their biofilms after treatment for 5 minutes and 2 hours respectively in the bactericidal efficacy study.The interaction between CPC-nanoparticles and staphylococcus aureus and pseudomonas aeruginosa biofilms was observed by confocal laser scanning microscope(CLSM). Result: 0.010%, 0.025% and 0.050% CPC-nanoparticles and CPC-micelle solutions had significant bactericidal effect on planktonic staphylococcus aureus and pseudomonas aeruginosa after fiveminute exposure(P<0.05), and staphylococcus aureus and pseudomonas aeruginosa biofilms after both five-minute and two-hour treatments(P<0.05). In CLSM study, the size of staphylococcus aureus biofilms decreased, while dead bacteria of pseudomonas aeruginosa biofilms increased after two-hour treatment. Conclusion: CPC-nanoparticles had significant bactericidal effects on staphylococcus aureus and pseudomonas aeruginosa biofilms, which could be used in treatment of CRS.


Light-Induced Polar pH Changes in Leaves of Elodea canadensis: II. Effects of Ferricyanide: Evidence for Modulation by the Redox State of the Cytoplasm.
The effect of an extracellular electron acceptor, ferricyanide, on the light-induced polar leaf pH changes of the submerged angiosperm Elodea canadensis in light and in darkness was determined. The rate of transmembrane ferricyanide reduction was stimulated by increased light intensity and was inhibited by inorganic carbon, indicating that changes in the redox state of the chloroplast were reflected at the plasma membrane. The addition of ferricyanide inhibited the light-induced polar leaf pH reaction. This effect could be balanced by increasing the light intensity. In the dark, the acidification induced by ferricyanide was not influenced by diethylstilbestrol at concentrations that completely inhibited the polar leaf pH changes. This indicates that the ferricyanide-induced H(+) extrusion and the H(+) transport during the polar reaction were mediated by different mechanisms.


Predictors of amyotrophic lateral sclerosis mimic syndrome.
The term amyotrophic lateral sclerosis mimic syndrome (ALSms) includes pathologies that present signs or symptoms similar to those caused by amyotrophic lateral sclerosis (ALS), which can lead to misdiagnosis. In general, any kind of misdiagnosis can result in negative clinical, psychological and economic consequences as well diagnostic and treatment delay. The objectives were to determine the frequency and to compare the demographic and clinical characteristics of patients with ALS and ALSms in our ALS clinic. We retrospectively studied all patients evaluated from 2007 to 2017 including only patients with a definite final diagnosis. Out of 368 patients with motor neuron disease symptomatology, 43 (11.7%) had an ALSms. The most frequent etiology was compressive myelopathy (32.6%). Multivariate analysis considering positive associations was statistically significant for patients having only upper or lower motor neuron signs in the physical examination, a non-compatible electromyogram (EMG), as well as atypical first symptoms. ALS misdiagnosis is an ongoing and not infrequent problem. From our series of patients, atypical symptoms, absence of EMG pathological findings or isolated upper or lower motor neuron disease should prompt suspicion of a differential diagnosis.


[Significance of electrocardiographic QRS width in patients with congestive heart failure: a marker for biventricular pacing].
Biventricular pacing may be valuable for the treatment of patients with intractable heart failure, but how many patients in Japan would benefit from this type of therapy remains uncertain. This study investigated the incidence of intraventricular conduction delay in the electrocardiogram(ECG) as a marker of the need for biventricular pacing, as well as the underlying etiology of heart failure in patients admitted with congestive heart failure. Patients with heart failure admitted to the Tokai University Hospital from January 1990 to September 2000 were studied retrospectively. The distribution of age, sex and underlying diseases, and that of the rhythm and the QRS width in ECG recordings were analyzed. Patients with a QRS width of over 121 msec in the ECG were classified as the 'wide QRS' group. Of a series of 1,200 consecutive patients with heart failure, 872 patients, 499 males and 373 females (mean age 67.9 +/- 13.9 years) were admitted to the hospital and 71 had 'wide QRS' by ECG. Among those in the 'wide QRS' group, 37% had ischemic heart disease and 14% had dilated cardiomyopathy. The widest QRS complexes were encountered in patients with dilated cardiomyopathy and the largest number of wide QRS complexes was encountered in patients with ischemic heart disease. The most frequent causes of heart failure among patients considered suitable for biventricular pacing were ischemic heart disease and dilated cardiomyopathy, which is consistent with previous reports. Compared with the statistics reported from western countries, the incidence of ischemic heart disease and the incidence of intraventricular conduction delay were lower in Japanese patients with heart failure. The incidence of intraventricular conduction delay among patients with heart failure was 8.6%. Therefore, fewer patients need biventricular pacing in Japan than in western countries. Nevertheless, patients with heart failure resistant to other therapies might still benefit from this type of therapy.


[Olavide and his work. The beginning of dermatology in Spain].
José Eugenio Olavide was the founder and promoter of Spanish dermatology, and the head of the first Department of Dermatology. He spread to his disciples the ideas of the French dermatology, especially Bazin and Hardy. He pioneered the application of laboratory techniques to diagnosis of skin diseases, being the founder of Olavide Museum, wich was of great distinction in Europe with 1500 wax models. This museum was open until the 60's, when it was closed and forgotten, being recovered in 2005 by the AEDV, wich is currently conducting its restoration. In the year 1872, Olavide becomes a member of the Royal Academy of Medicine with the speech "Parasitism or morbidly plant to reason and to facts" answered by Mariano Benavente. He owned the chair number 33 of this institution.


The Benefits of Resistance Training in Obese Adolescents: A Systematic Review and Meta-analysis.
Physical activity is essential in acquiring healthy lifestyle behaviors in the early years of maturational development and preventing various diseases. Resistance training (RT) is fundamental for improving body composition and is increasingly recommended for obese adolescents. A systematic review and meta-analysis were performed to synthesize and analyze data on the effects of RT programs in this population, seeking to develop useful recommendations for health and sports professionals. A search was performed using four databases (Web of Science, Scopus, PubMed, and ScienceDirect). According to specific inclusion criteria, twenty-one studies were selected to evaluate the impact of RT on body mass index (BMI), body fat, waist circumference, muscle strength, insulin sensitivity, lean mass and cardiorespiratory fitness. After the RT programs, the adolescents improved their muscle strength (SMD, 1.44; 95% CI: 0.76-2.12), cardiorespiratory fitness (SMD, 1.09; 95% CI: 0.15-2.04), BMI (SMD, 0.21; 95% CI: 0.07-0.35), waist circumference (SMD, 0.27; 95% CI: 0.06-0.47) and body fat (SMD, 0.20; 95% CI: 0.05-0.34). However, insulin sensitivity (SMD, 0.32; 95% CI: - 0.47 to 1.10) and lean mass (SMD, 0.12; 95% CI: - 0.06 to 0.31) did not reveal any changes. Different RT programs were used but it seems that 2-3 times/week ∼60 min/session of RT for 12 weeks should be recommended for positive changes. RT seems to be effective when the objective is to improve muscle strength, cardiorespiratory fitness and can be an efficient strategy to reduce obesity in adolescents by reducing body fat, waist circumference and body mass index. PROSPERO Registration number: CRD42022333411.


New diarylheptanoids and diarylheptanoid glucosides from the rhizomes of Tacca chantrieri and their cytotoxic activity.
Two new diarylheptanoids (1, 2) and seven new diarylheptanoid glucosides (3-9) were isolated from the rhizomes of Tacca chantrieri. Their structures were determined by spectroscopic analysis, including 2D NMR data, and the results of hydrolytic cleavage. The absolute configurations of the 3,5-dihydroxyheptane moieties of the new diarylheptanoids were determined to be 3R and 5R by the application of the CD exciton chirality method to the corresponding 3,5-bis-p-bromobenzoyl derivatives. The cytotoxic activities of the isolated compounds and some derivatives against HL-60 human promyelocytic leukemia cells, HSC-2 human oral squamous carcinoma cells, and normal human gingival fibroblasts (HGF) are reported.


Prediction Modeling of Mental Well-Being Using Health Behavior Data of College Students.
Background: Since the onset of the COVID-19 pandemic in early 2020, the importance of timely and effective assessment of mental well-being has increased dramatically. Due to heightened risks for developing mental illness, this trend is likely to continue during the post-pandemic period. Machine learning (ML) algorithms and artificial intelligence (AI) techniques can be harnessed for early detection, prognostication and prediction of negative psychological well-being states. Objective: Studies using machine learning classification of mental well-being are scarce in Asian populations. This investigation aims to develop reliable machine learning classifiers based on health behavior indicators applicable to university students in South-East Asia. Methods: Using data from a large, multi-site cross-sectional survey, this research work models mental well-being and reports on the performance of various machine learning algorithms, such as generalized linear models, k-nearest neighbor, naïve-Bayes, neural networks, random forest, recursive partitioning, bagging, and boosting. Prediction models were evaluated using various metrics such as accuracy, error rate, kappa, sensitivity, specificity, Area Under the recursive operating characteristic Curve (AUC), and Gini Index. Results: Random forest and adaptive boosting algorithms achieved the highest accuracy of identifying negative mental well-being traits. The top five most salient features associated with predicting poor mental well-being include body mass index, number of sports activities per week, grade point average (GPA), sedentary hours, and age. Conclusions: Based on the reported results, several specific recommendations and suggested future work are discussed. These findings may be useful to provide cost-effective support and modernize mental well-being assessment and monitoring at the individual and university level.


Wunderlich's syndrome and hemorrhagic shock.
We report a case of Wunderlich's syndrome in an obese woman associated with massive retroperitoneal hemorrhage. Stable hemodynamic patient condition was obtained by selective arterial embolization. Since the first embolization of a renal angiomyolipoma in 1976 by Moorhead et al., highly selective renal arterial embolization of angiomyolipoma with rupture has become a procedure that offers greater efficacy, particularly in life-threatening cases.


Linear superposition in nonlinear equations.
Several nonlinear systems such as the Korteweg-de Vries (KdV) and modified KdV equations and lambda phi(4) theory possess periodic traveling wave solutions involving Jacobi elliptic functions. We show that suitable linear combinations of these known periodic solutions yield many additional solutions with different periods and velocities. This linear superposition procedure works by virtue of some remarkable new identities involving elliptic functions.


Apoptosis of retinal photoreceptors during development in vitro: protective effect of docosahexaenoic acid.
When rat retinal cells are cultured in a serum-free medium, the photoreceptor cells start dying after 7 days. The addition of docosahexaenoic acid (DHA) to the cultures prevents the selective death of photoreceptors. Here it is shown that, unlike other retinal neurons, photoreceptors die through an apoptotic pathway. Hallmarks of apoptosis, such as nuclear fragmentation and condensation and DNA cleavage forming a ladder pattern on an agarose gel, were observed. The timing and high selectivity of the triggering of photoreceptor cell apoptosis suggest the existence of a programmed cell death. Compared with other fatty acids, DHA not only was the most effective in promoting photoreceptor survival, but also the only one to decrease the number of apoptotic nuclei. The results suggest that DHA is important among the factors preventing apoptosis of photoreceptors in the developing retina. A limitation in the availability of this fatty acid might trigger apoptosis as a result of the failure to develop functional photoreceptor outer segments.


A Sarcocystis neurona-like organism associated with encephalitis in a striped skunk (Mephitis mephitis).
A Sarcocystis neurona-like organism was associated with granulomatous encephalitis in an ataxic male juvenile striped skunk (Mephitis mephitis) from Cape Cod, Massachusetts. Various stages of schizonts and merozoites of S. neurona were seen within some of the granulomata.


Finger millet (Eleucine coracana) flour as a vehicle for fortification with zinc.
Millets, being less expensive compared to cereals and the staple for the poorer sections of population, could be the choice for fortification with micronutrients such as zinc. In view of this, finger millet, widely grown and commonly consumed in southern India, was explored as a vehicle for fortification with zinc in this investigation. Finger millet flour fortified with either zinc oxide or zinc stearate so as to provide 50mg zinc per kg flour, was specifically examined for the bioaccessibility of the fortified mineral, as measured by in vitro simulated gastrointestinal digestion procedure and storage stability. Addition of the zinc salts increased the bioaccessible zinc content by 1.5-3 times that of the unfortified flour. Inclusion of EDTA along with the fortified salt significantly enhanced the bioaccessibility of zinc from the fortified flours, the increase being three-fold. Inclusion of citric acid along with the zinc salt and EDTA during fortification did not have any additional beneficial effect on zinc bioaccessiblity. Moisture and free fatty acid contents of the stored fortified flours indicated the keeping quality of the same, up to 60 days. Both zinc oxide and zinc stearate were equally effective as fortificants, when used in combination with EDTA as a co-fortificant. The preparation of either roti or dumpling from the fortified flours stored up to 60 days did not result in any significant compromise in the bioaccessible zinc content. Thus, the present study has revealed that finger millet flour can effectively be used as a vehicle for zinc fortification to derive additional amounts of bioaccessible zinc, with reasonably good storage stability, to combat zinc deficiency.


Enantioselective α-alkenylation of aldehydes with boronic acids via the synergistic combination of copper(II) and amine catalysis.
The enantioselective α-alkenylation of aldehydes has been accomplished using boronic acids via the synergistic combination of copper and chiral amine catalysis. The merger of two highly utilized and robust catalytic systems has allowed for the development of a mild and operationally trivial protocol for the direct formation of α-formyl olefins employing common building blocks for organic synthesis.


Transgenic expression of CXCR3 on T cells enhances susceptibility to cutaneous Leishmania major infection by inhibiting monocyte maturation and promoting a Th2 response.
Cutaneous leishmaniasis, caused mainly by Leishmania major, an obligate intracellular parasite, is a disfiguring disease characterized by large skin lesions and is transmitted by a sand fly vector. We previously showed that the chemokine receptor CXCR3 plays a critical role in mediating resistance to cutaneous leishmaniasis caused by Leishmania major. Furthermore, T cells from L. major-susceptible BALB/c but not L. major-resistant C57BL/6 mice fail to efficiently upregulate CXCR3 upon activation. We therefore examined whether transgenic expression of CXCR3 on T cells would enhance resistance to L. major infection in susceptible BALB/c mice. We generated BALB/c and C57BL/6 transgenic mice, which constitutively overexpressed CXCR3 under a CD2 promoter, and then examined the outcomes with L. major infection. Contrary to our hypothesis, transgenic expression of CXCR3 (CXCR3(Tg)) on T cells of BALB/c mice resulted in increased lesion sizes and parasite burdens compared to wild-type (WT) littermates after L. major infection. Restimulated lymph node cells from L. major-infected BALB/c-CXCR3(Tg) mice produced more interleukin-4 (IL-4) and IL-10 and less gamma interferon (IFN-γ). Cells in draining lymph nodes from BALB/c-CXCR3(Tg) mice showed enhanced Th2 and reduced Th1 cell accumulation associated with increased neutrophils and inflammatory monocytes. However, monocytes displayed an immature phenotype which correlated with increased parasite burdens. Interestingly, transgenic expression of CXCR3 on T cells did not impact the outcome of L. major infection in C57BL/6 mice, which mounted a predominantly Th1 response and spontaneously resolved their infection similar to WT littermates. Our findings demonstrate that transgenic expression of CXCR3 on T cells increases susceptibility of BALB/c mice to L. major.


A serotonin receptor antagonist induces oocyte maturation in both frogs and mice: evidence that the same G protein-coupled receptor is responsible for maintaining meiosis arrest in both species.
Accumulating evidence has indicated that vertebrate oocytes are arrested at late prophase (G2 arrest) by a G protein coupled receptor (GpCR) that activates adenylyl cyclases. However, the identity of this GpCR or its regulation in G2 oocytes is unknown. We demonstrated that ritanserin (RIT), a potent antagonist of serotonin receptors 5-HT2R and 5-HT7R, released G2 arrest in denuded frog oocytes, as well as in follicle-enclosed mouse oocytes. In contrast to RIT, several other serotonin receptor antagonists (mesulergine, methiothepine, and risperidone) had no effect on oocyte maturation. The unique ability of RIT, among serotonergic antagonists, to induce GVBD did not match the antagonist profile of any known serotonin receptors including Xenopus 5-HT7R, the only known G(s)-coupled serotonin receptor cloned so far in this species. Unexpectedly, injection of x5-HT7R mRNA in frog oocytes resulted in hormone-independent frog oocyte maturation. The addition of exogenous serotonin abolished x5-HT7R-induced oocyte maturation. Furthermore, the combination of x5-HT7R and exogenous serotonin potently inhibited progesterone-induced oocyte maturation. These results provide the first evidence that a G-protein coupled receptor related to 5-HT7R may play a pivotal role in maintaining G2 arrest in vertebrate oocytes.


The effects of the hypothalamus on hemodynamic changes elicited by vagal nerve stimulation.
To investigate the means by which neurogenic shock or syncope occur in dentistry, we determined the hemodynamic response to the activation of vagal tone in cats while they were under emotional stress. The hypothalamus and the vagal nerve were electrically stimulated to produce emotional stress and to activate vagal tone, respectively. Hemodynamic changes were recorded during vagal stimulation (Va group) and during vagal stimulation preceded by hypothalamic stimulation (AH + Va group). Although blood pressure decreased in both groups, the degree of hypotensive response in the AH + Va group was greater than the response in the Va group. Total peripheral resistance (TPR) was reduced in the AH + Va group but was increased in the Va group. The blood flow to the skeletal muscles in the AH + Va group was greater than that of the Va group. Reduced TPR, which could be due to vasodilation in the skeletal muscles, was the cause of intensified hypotension in the AH + Va group. Clearly, the hypotension produced by vagal stimulation was worsened when it was preceded by hypothalamic stimulation; this occurrence could be related to the tendency of blood to flow to the skeletal muscles.


Alkylamides as inducers of human leukemia cell differentiation: a quantitative structure-activity relationship study using comparative molecular field analysis.
Computer assisted quantitative structure-activity studies using comparative molecular field analysis (CoMFA) were performed on a series of alkylamides that induce cell differentiation. The series included alkylformamides, alkylacetamides, alkylureas, and substituted hexyl analogues of acetamide. The biological activity studied for correlation with structure was the ability of each compound to induce differentiation of the human promyelocytic leukemia cell line, HL-60, to granulocyte-like cells. In the CoMFA study, both steric and electrostatic fields were used along with molecular weight to determine a correlation between biological activity of the compounds and their structural features. The CoMFA results indicated a linear structure-activity correlation with a high predictive value. There was almost an even contribution towards activity from steric interactions, electrostatic potential, and molecular weight. These findings confirm a previous report by Langdon and Hickman (S. P. Langdon and J. A. Hickman, Cancer Res., 47: 140-144, 1987) that the ability to induce cell differentiation is highly dependent on molecular weight. Additionally, CoMFA contour maps provided information about regions of the molecule that are favorable to increased steric bulk and electrostatic charge. CoMFA was used to predict the activities of six hexamethylene acetamide analogues: ethyl 6-acetamidohexanoate; 6-acetamidohexanol; 1,5-bis(acetamido)hexane; 6-acetamidohexanonitrile; 6-acetamidohexanoic acid; and caprolactam. Although the model incorrectly predicted high activity for 6-acetamidohexanoic acid, the predicted activities for the remaining compounds were 0.3 to 1.5 times that of the corresponding experimental activities, which is comparable to the results obtained from other published CoMFA studies.


Alcoholism: early diagnosis and intervention.
Alcoholism, more than any other illness, requires the integration of social and family history, physical symptoms and signs, and laboratory data in order to make a firm diagnosis. Common in alcoholism is the patient's minimization or denial of the disease and its symptoms, thwarting efforts at early diagnosis and intervention. If early diagnosis is to be made, several points should be remembered: 1. Life problems associated with alcohol use are the earliest signs of the disease. 2. There are few reliable early physical symptoms and signs. 3. Laboratory markers of alcoholism are neither sensitive nor specific when used alone as screening tools. 4. Alcoholism questionnaires, e.g., the MAST or the CAGE, should be a part of routine office practice in screening for alcoholism. Effective therapy is available, but early diagnosis is necessary for the best outcome. Gallant has reminded us of the "tragedy of delayed treatment." Early recognition of alcoholism puts the internist, as well as other primary care providers, in the best position to begin the process of healing the patients and their families.


Size of households and income disparities.
The author examines "the relation between differentials in size of households, (preponderantly family households including one-person units) and disparities in income per household, per person, or per some version of consuming unit." The analysis is based on data for the United States, the Federal Republic of Germany, Israel, Taiwan, the Philippines, and Thailand.


Detecting duplicate biological entities using Shortest Path Edit Distance.
Duplicate entity detection in biological data is an important research task. In this paper, we propose a novel and context-sensitive Shortest Path Edit Distance (SPED) extending and supplementing our previous work on Markov Random Field-based Edit Distance (MRFED). SPED transforms the edit distance computational problem to the calculation of the shortest path among two selected vertices of a graph. We produce several modifications of SPED by applying Levenshtein, arithmetic mean, histogram difference and TFIDF techniques to solve subtasks. We compare SPED performance to other well-known distance algorithms for biological entity matching. The experimental results show that SPED produces competitive outcomes.


The prevalence of familial hyperaldosteronism in apparently sporadic primary aldosteronism in Germany: a single center experience.
Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. To date 3 forms of familial hyperaldosteronism (FH) have been described accounting for a small percentage of all PA cases. In Germany, the prevalence of FH is currently unknown. Our aim was to determine the prevalence of familiarity in a large cohort of patients with PA. A total of 166 patients with apparently sporadic PA in Munich were investigated. FH types I, II, and III were identified using established clinical, biochemical, and molecular criteria. Among the 166 patients with PA, 2 patients (1.2%) reported a family history suggestive of FH. None of the 166 patients showed clinical, endocrine, or genetic evidence of FH type I. The 2 families had characteristic features of FH type II. Family A had 3 subjects affected out of 11 evaluated family members. Family B had 3 out of 4. Bilateral adrenal hyperplasia and unilateral adrenal adenoma were found within the same family. FH type I and FH type III are rare in Germany. With a prevalence of 1.2%, FH type II seems to be more common in apparently sporadic PA than had been assumed so far.


Democratizing the hospital: deliberative-democratic bioethics.
The increased presence of moral consultants, or bioethicists, within hospitals and clinics in the last two decades has begun to raise questions about their sources of authority and norms of practice. Under pressure from critics in the social sciences, a number of bioethicists have recently raised the ideal of democratic deliberation to defend and reconstruct their place in the medical field. This article sheds light on these developments by placing bioethics in a historical context that shows an early tension between bioethicists as whistle-blowers and bioethicists as incremental reformers of medical practice. This article also develops a conceptual framework for analysis that indicates how such tensions have grown more complicated for contemporary bioethicists because they occupy a fluid and structurally ambiguous role in which there are multiple sources of normative expectations and little guidance for meeting these expectations. The liminality of the role and the overload of expectations have made bioethics vulnerable to methodological criticisms from social scientists. This article concludes that such methodological criticisms cannot address the more systemic problems of liminality and overload. The ideal of democratic deliberation, though imperfect, does address these systemic problems because it shows bioethicists how to gain guidance and share responsibility for moral consultation.


Twelve tips for developing feedback literacy in health professions learners.
Despite feedback being widely-used by health professions educators as a tool to develop clinical competencies, strategies to guide its successful implementation remain limited. In addition, health professions learners are often dissatisfied with the quality and/or volume of feedback they receive. Efforts to better engage learners in feedback processes have resulted in the development of a number of theoretical frameworks to guide educators, one being feedback literacy. Feedback literacy can be conceptualised as a learner's ability to recognise, comprehend, generate, and take action on feedback they encounter during their learning to aid health professions learners' clinical competency development. Here, we draw on both a conceptual framework of feedback literacy and other contemporary feedback literature to provide 12 practical tips by which feedback literacy can be developed in health professions learners.


First host record of Myopa pellucida Robineau-Desvoidy (Diptera: Conopidae) identified using DNA barcoding.
Thick-headed flies of the genus Myopa Fabricius are a common sight in early spring in Europe. Several species can be found flying among Salix catkins together with their supposed Andrena Fabricius hosts (Hymenoptera: Apidae) (John Smit observations). Despite the fact that some of these Myopa species are very common, little is known about their actual host-parasitoid associations. Only a few scattered host records can be found in the literature, most of which refer to M. testacea s.l.. Whether or not these records actually concern M. testacea (Linnaeus) is uncertain due to the confusion over the identity of several species within the M. testacea species group (Stuke Clements 2008). Stuke (2017), in his World Catalogue of Conopids, provides all recorded host associations and distinguishes between unambiguously accepted host records and doubtful records based on three criteria: 1) the conopid has been reared from the host or a larva has been identified by DNA barcoding; 2) there is no doubt concerning the identity of the conopid species concerned, and 3) there is no doubt concerning the identity of the host species. Because the vast majority of the host records in the literature do not fulfil one or more of these criteria they are regarded as doubtful (Stuke 2017). Thus, only three host associations for the genus Myopa can be regarded as confirmed: Andrena vaga Panzer, for both M. hirsuta Stuke Clements (Jentzsch 2009) and M. testacea (Erteld 1998, Fellendorf et al. 2004, De Meijere 1912), and the Nearctic Andrena regularis Malloch, for the Holarctic M. vicaria Walker (Miliczky Osgood 1995). Here we report on a fourth host association for the genus Myopa, since a second instar larva of M. pellucida Robineau-Desvoidy was found in the abdomen of an Andrena nitida (Müller) female and identified using DNA barcoding.


A comparison of four aqueous-miscible liquid scintillation cocktails with an alpha/beta discriminating Wallac 1415 liquid scintillation counter.
This work was directed towards an assessment of alpha/beta separation, alpha detection efficiency, energy resolution, quench sensitivity, and background count rate for four commercially available liquid scintillation cocktails using a Wallac 1415 liquid scintillation counter. The four cocktails were Wallac Oy OptiPhase HiSafe 3 and HiSafe 2, and Packard Ultima Gold AB and Ultima Gold XR. Aqueous radioactive solutions were prepared in 0.1 N HCl and contained 241Am (5.49 MeV alpha) and 90Sr/90Y (0.46/2.28 MeV beta-). The radioactive solutions were loaded into the cocktails at a ratio of 1 mL of aqueous solution to 10 mL of cocktail in 20 mL high-density polyethylene (HDPE) liquid scintillation vials. The effect of three levels of chemical quench on the various properties of interest was assessed for each of the LS cocktails. Alpha/beta discrimination was quantified by the fraction of beta interactions that "spillover" into the alpha window and vice versa, at the working discriminator setting. The working discriminator setting was defined as the point where the spillover of beta interactions into the alpha window and alpha interactions into the beta window were equal. For the low-quench samples, Ultima Gold AB had the lowest spillover (0.25%) and Ultima Gold XR had the highest spillover (0.8%). For the high-quench samples, the spillover ranged from 4% (HiSafe 3) to 10.5% (Ultima Gold XR). The detection efficiency for 241Am was nearly 100% and decreased with increased quench because of loss from spillover. HiSafe 2 gave the best energy resolution, 500 keV (FWHM), for the low-quench sample. The lowest background count rate was achieved with Ultima Gold AB, 0.056 cpm in the 241Am window, for a low-quench blank.


Butyltin compounds in human liver.
Intake of marine food is the main source of butyltin exposure in humans. Health effects following exposure to butyltin compounds are usually in the immune system, but endocrine effects of butyltin from a variety of marine species have been documented. The information on human exposure to butyltin compounds and hepatic deposition is limited. The present study include 18 consecutively sampled human livers analyzed for butyltin compounds. Dibutyltin (DBT) concentrations varied between 0.8 and 28.3 ng/g with a mean concentration of 9.0 ng/g. Significantly lower concentrations of monobutyltin (MBT) were observed, ranging from 0.3 to 4.7 ng/g with a mean value of 1.6 ng/g. Age and DBT/MBT ratio were significantly associated. We suggest that younger men have more recent exposures or have a lower capacity to debutylate DBT than older men and would therefore potentially be more susceptible to butyltin toxicity. Given the interperson variability observed in our limited group of men, we cannot exclude that thresholds for either immunotoxicity or effects on the endocrine system may occur due to exposure to butyltin compounds alone or in combination with other environmental toxicants with similar target organs.


Identification, Prediction and Data Analysis of Noncoding RNAs: A Review.
Noncoding RNAs (ncRNAs) which play an important role in various cellular processes are important in medicine as well as in drug design strategies. Different studies have shown that ncRNAs are dis-regulated in cancer cells and play an important role in human tumorigenesis. Therefore, it is important to identify and predict such molecules by experimental and computational methods, respectively. However, to avoid expensive experimental methods, computational algorithms have been developed for accurately and fast prediction of ncRNAs. The aim of this review was to introduce the experimental and computational methods to identify and predict ncRNAs structure. Also, we explained the ncRNA's roles in cellular processes and drugs design, briefly. In this survey, we will introduce ncRNAs and their roles in biological and medicinal processes. Then, some important laboratory techniques will be studied to identify ncRNAs. Finally, the state-of-the-art models and algorithms will be introduced along with important tools and databases. The results showed that the integration of experimental and computational approaches improves to identify ncRNAs. Moreover, the high accurate databases, algorithms and tools were compared to predict the ncRNAs. ncRNAs prediction is an exciting research field, but there are different difficulties. It requires accurate and reliable algorithms and tools. Also, it should be mentioned that computational costs of such algorithm including running time and usage memory are very important. Finally, some suggestions were presented to improve computational methods of ncRNAs gene and structural prediction.


Turbulent Aggregation and Deposition Mechanism of Respirable Dust Pollutants under Wet Dedusting using a Two-Fluid Model with the Population Balance Method.
In this paper, a mathematical model based on the two-fluid (Euler-Euler) frame model for wet dedusting process is proposed. The model considers in detail the aggregation of particles and droplets caused by turbulence and Brownian diffusion as well as the gravitational deposition process. The population balance model (PBM) is used to describe the spatiotemporal evolution of particle size distribution (PSD) for the dust particle and the water droplet. The wet dedusting process under different conditions is simulated and compared with the detailed experimental data. The results show that the experimental data and simulation results are within the allowable range of error (about 32.3-61.2% in dedusting efficiency for respirable dust by experimental data and about 47.3-57.9% in it by simulation results). This model can be used to predict the effect of PSD of the dust particle, spray flow, and ventilation rate on dedusting efficiency of wet dedusting. The parameter analysis shows that dedusting efficiency decreases as particle size decreases. In order to ensure high capture efficiency of respirable dust, the diameter of droplets should be controlled to between 15μm and 70μm. The ratio of droplet volume flow to dust volume flow increases from 2.0 to 12.0, while dedusting efficiency only increases from 39.2% to 54.7%, so it is clear that for spray quantity to dedusting efficiency, larger is not necessarily better. Besides this, the speeds of both spray droplets and ventilation also have great influence on dedusting efficiency, and the related formulas are given.


TiO2-derived titanate nanotubes by hydrothermal process with acid treatments and their microstructural evaluation.
In this study, the effect of post acid treatments with HCl aqueous solutions after the hydrothermal process on the microstructure of TiO2-derived titanate nanotube was investigated. Especially, the relationship between local structural changes with the HCl treatment and their thermal stability were investigated by X-ray absorption fine structure (XAFS). Consequently, it revealed that the replacement of Na+ with H+ (proton exchange) in TiO2-derived titanate nanotubes was caused by the acid treatment with HCl aqueous solutions and the excess acid treatment led to the disordering. Moreover, it was confirmed that the minor change of TiOx polyhedra in TiO2-derived titanate nanotubes was also related with this disordering.


[Diagnostic and therapeutic control of varicoceles using angiodynography].
We report on the results of angiodynography of 21 patients with suspected varicoceles. In 14 cases a varicocele could be diagnosed. Additionally, 19 patients underwent conventional Doppler sonography (16 with positive findings), 7 thereof also a testicular phlebography (5 positive findings). Thus, in conventional Doppler sonography there were 2 false positive findings. With angiodynography it was possible to detect an existing varicocele in all 14 (of the 21) cases even if only a small retrograde flow existed. In 11 of the cases this could be graded with the help of the flow velocity. In case of negative findings in angiodynography, further invasive techniques are unnecessary. However, before embolisation of a varicocele and to show preoperatively vessel variations or collateral vessels, testicular phlebography is still indicated.


A formal [3 + 2] annulation reaction of propargyl sulfonium compounds and N-ylides: access to pyrrolo[2,1-a]quinolines, pyrrolo[2,1-a]phthalazines and indolizines.
A sequential [3 + 2] annulation of prop-2-ynylsulfonium salt and N-ylides was developed, leading to the formation of a series of pyrrolo[2,1-a]quinolines, pyrrolo[2,1-a]phthalazines and indolizines. The protocol featured the simultaneous one-pot formation of three new C-C bonds in moderate yields under mild conditions. In this reaction, the prop-2-ynylsulfonium salts acted as the C2 synthons and sulfide served as the leaving group. The resultant products could serve as useful precursors for the synthesis of diverse chemical compounds.


Speckle reduction by simulation of partially coherent object illumination in holography.
This method consists of two steps. The first is to illuminate the object with a plurality of point sources each of which is mutually coherent with the reference source. All the points are contained within the pupil of the optical apparatus. The second step takes place after the hologram has been made in the manner mentioned. During the reconstruction, a mask is placed in the plane, conjugate to the plane containing the plurality of object-illuminating sources. An aperture in this mask is then moved to take positions to transmit only the light from one of the plurality of points at a time and to block the light from all the other points. The images thus detected are additive in intensity, simulating the plurality of illuminating point sources to be mutually incoherent.


Pharmacogenetics in colorectal cancer: a systematic review.
Pharmacological treatment of colorectal cancer has improved survival rates in recent years. Individual genetic variation in genes associated with metabolism and targets of commonly used drugs can be responsible for variability in treatment outcome and toxicity. Diverse study designs have been used and heterogeneous end points evaluated by studies assessing the association of genetic markers with treatment outcome. We conducted this systematic review, including 51 studies, to present a comprehensive overview and draw further conclusions. To facilitate comparison of reported study results, risk estimates for observed genetic variants in 33 key genes are presented using defined reference categories and recalculated risk estimates based on data provided in original publications, where necessary. Overall, evidence indicates associations of the UGT1A1(*) 28 variant genotype with toxicity after irinotecan treatment, mutations in GSTP1-105 with improved treatment outcome and the XPD-751 variant genotype with poor treatment outcome after oxaliplatin treatment, and amplification of the EGFR gene with improved treatment outcome after therapy with monoclonal antibodies. Adequately powered prospective investigations designed specifically for pharmacogenetics are needed.


Iridium(I)-Catalyzed C-C and C-N Bond Formation Reactions via the Borrowing Hydrogen Strategy.
Iridium(I) complexes having an imidazol-2-ylidene ligand with benzylic wingtips efficiently catalyzed the β-alkylation of secondary alcohols with primary alcohols and acceptorless dehydrogenative cyclization of 2-aminobenzyl alcohol with ketones through a borrowing hydrogen pathway. The β-alkylated alcohols, including cholesterol derivatives, and substituted quinolines were obtained in good yields by using a minute amount of the catalyst with a catalytic amount of NaOH or KOH under the air atmosphere, liberating water (and H2 in the case of quinoline synthesis) as the sole byproduct. Notably, this system demonstrated turnover numbers of 940 000 (for β-alkylation of secondary alcohols with primary alcohols by using down to 0.0001 mol % = 1 ppm of the catalyst) and 9200 (acceptorless dehydrogenative cyclization of 2-aminobenzyl alcohol with ketones).


Conflicting roles for a cell surface modification in Salmonella.
Chemical modifications of components of the bacterial cell envelope can enhance resistance to antimicrobial agents. Why then are such modifications produced only under specific conditions? Here, we address this question by examining the role of regulated variations in O-antigen length in the lipopolysaccharide (LPS), a glycolipid that forms most of the outer leaflet of the outer membrane in Gram-negative bacteria. We determined that activation of the PmrA/PmrB two-component system, which is the major regulator of LPS alterations in Salmonella enterica serovar Typhimurium, impaired growth of Salmonella in bile. This growth defect required the PmrA-activated gene wzz(st), which encodes the protein that determines long O-antigen chain length and confers resistance to complement-mediated killing. By contrast, this growth defect did not require the wzz(fepE) gene, which controls production of very long O-antigen, or other PmrA-activated genes that mediate modifications of lipid A or core regions of the LPS. Additionally, we establish that long O-antigen inhibits growth in bile only in the presence of enterobacterial common antigen, an outer-membrane glycolipid that contributes to bile resistance. Our results suggest that Salmonella regulates the proportion of long O-antigen in its LPS to respond to the different conditions it faces during infection.


Shear mode coupling and tilted grain growth of A1N thin films in BAW resonators.
Polycrystalline A1N thin films were deposited by RF reactive magnetron sputtering on Pt(111)/Ti electrode films. The substrates were tilted by an angle ranging from 40 degrees to 70 degrees with respect to the target normal. A low deposition temperature and a high sputter gas pressure were found ideal for tilted growth. The resulting grain tilt angle amounts to about half the substrate tilt angle. For coupling evaluation, 5 GHz solidly mounted resonator structures have been realized. The tilted grain A1N films exhibited a permittivity in the 9.5-10.5 range and loss tangent of 0.3%. Two shear modes as well as the longitudinal mode could be clearly identified. The coupling coefficient k2(eff) of the fundamental thickness shear mode (TS0) was found to be about 0.5%, which is compatible with a c-axis tilt of about 6 degrees.


Galactosylated chitosan oligosaccharide nanoparticles for hepatocellular carcinoma cell-targeted delivery of adenosine triphosphate.
Nanoparticles composed of galactosylated chitosan oligosaccharide (Gal-CSO) and adenosine triphosphate (ATP) were prepared for hepatocellular carcinoma cell-specific uptake, and the characteristics of Gal-CSO/ATP nanoparticles were evaluated. CSO/ATP nanoparticles were prepared as a control. The average diameter and zeta potential of Gal-CSO/ATP nanoparticles were 51.03 ± 3.26 nm and 30.50 ± 1.25 mV, respectively, suggesting suitable properties for a drug delivery system. Subsequently, the cytotoxicity of Gal-CSO/ATP nanoparticles were examined by the methyl tetrazolium (MTT) assay, and the half maximal inhibitory concentration (IC50) values were calculated with HepG2 (human hepatocellular carcinoma cell line) cells. The results showed that the cytotoxic effect of nanoparticles on HepG2 cells was low. In the meantime, it was also found that the Gal-CSO/ATP nanoparticles could be uptaken by HepG2 cells, due to expression of the asialoglycoprotein receptor (ASGP-R) on their surfaces. The presented results indicate that the Gal-CSO nanoparticles might be very attractive to be used as an intracellular drug delivery carrier for hepatocellular carcinoma cell targeting, thus warranting further in vivo or clinical investigations.


Surfactant sufficiency for immature infants--prenatal induction vs. postnatal treatment.
The prenatal and postnatal therapeutic management of surfactant insufficiency are reviewed. Prenatal maternal glucocorticoid therapy promotes lung maturation and enhances lung surfactant levels in the neonate, but a minimum of 24 hr treatment is required and the therapy is of limited effectiveness even under optimal conditions. Relatively few women in premature labour are good candidates for glucocorticoid therapy. Research into combinations of glucocorticoids with hormones (e.g. thyroid), and adrenergic agents in progress. The authors are studying the effects of fibroblast-pneumonocyte factor (FPF) on the fetal lung surfactant system. Postnatal therapy with insufflated natural and artificial surfactants has been studied in several centres with varying degrees of success. Currently, the risk:benefit ratios favour attempts to reduce the risks of respiratory distress syndrome (RDS) by both prenatal surfactant induction and postnatal replacement therapy. Greater understanding of the underlying mechanisms should permit the establishment of more satisfactory treatment.


Numerical simulation of diffusion processes at recessed disk microelectrode arrays using the quasi-conformal mapping approach.
In this work, we present a theoretical analysis of diffusion processes at arrays of recessed microelectrodes and evaluate the dependence of these processes on the main geometrical parameters (distance between electrodes in the array and slope of side walls of conical recesses) of this complex system. To allow for faster computation time and excellent accuracy, numerical simulations were performed upon transforming the real space allowed for diffusion using a quasi-conformal mapping introduced for this array geometry in our previous work (Amatore, C., Oleinick, A. I. and Svir, I. J. Electroanal. Chem. 2006, 597, 77-85). The applied quasi-conformal mapping is perfectly suited to the considered microelectrode array geometry and ensures that the abrupt change of boundary conditions reflecting the contorted geometries of the considered microelectrode array are treated efficiently and precisely in the simulations.


Variation in Surgical Antibiotic Prophylaxis for Outpatient Pediatric Urological Procedures at United States Children's Hospitals.
Guidelines recommend surgical antibiotic prophylaxis for clean-contaminated procedures but none for clean procedures. The purpose of this study was to describe variations in surgical antibiotic prophylaxis for outpatient urological procedures at United States children's hospitals. Using the PHIS (Pediatric Health Information System®) database we performed a retrospective cohort study of patients younger than 18 years who underwent clean and/or clean-contaminated outpatient urological procedures from 2012 to 2014. We excluded those with concurrent nonurological procedures or an abscess/infected wound. We compared perioperative antibiotic charges for clean vs clean-contaminated procedures using a multilevel logistic regression model with a random effect for hospital. We also examined whether hospitals that were guideline compliant for clean procedures, defined as no surgical antibiotic prophylaxis, were also compliant for clean-contaminated procedures using the Pearson correlation coefficient. We examined hospital level variation in antibiotic rates using the coefficient of variation. A total of 131,256 patients with a median age of 34 months at 39 hospitals met study inclusion criteria. Patients undergoing clean procedures were 14% less likely to receive guideline compliant surgical antibiotic prophylaxis than patients undergoing clean-contaminated procedures (OR 0.86, 95% CI 0.84-0.88, p <0.0001). Hospitals that used antibiotics appropriately for clean-contaminated procedures were more likely to use antibiotics inappropriately for clean procedures (r = 0.7, p = 0.01). Greater variation was seen for hospital level compliance with surgical antibiotic prophylaxis for clean-contaminated procedures (range 9.8% to 97.8%, coefficient of variation 0.36) than for clean procedures (range 35.0% to 98.2%, coefficient of variation 0.20). Hospitals that used surgical antibiotic prophylaxis appropriately for clean-contaminated procedures were likely to use surgical antibiotic prophylaxis inappropriately for clean procedures. More variation was seen in hospital level guideline compliance for clean-contaminated procedures.


Enhancement of Osteoblast Differentiation Using No-Ozone Cold Plasma on Human Periodontal Ligament Cells.
Periodontitis is an inflammatory disease that leads to periodontal tissue destruction and bone resorption. Proliferation and differentiation of cells capable of differentiating into osteoblasts is important for reconstructing periodontal tissues destroyed by periodontitis. In this study, the effects of the nozone (no-ozone) cold plasma (NCP) treatment on osteoblastic differentiation in periodontal ligament (PDL) cells were investigated. To test the toxicity of NCP on PDL cells, various NCP treatment methods and durations were tested, and time-dependent cell proliferation was analyzed using a water-soluble tetrazolium salts-1 assay. To determine the effect of NCP on PDL cell differentiation, the cells were provided with osteogenic media immediately after an NCP treatment to induce differentiation; the cells were then analyzed using alkaline phosphatase (ALP) staining, an ALP activity assay, real time PCR, and Alizarin Red S staining. The NCP treatment without toxicity on PDL cells was the condition of 1-min NCP treatment immediately followed by the replacement with fresh media. NCP increased ALP, osteocalcin, osteonectin, and osteopontin expression, as well as mineralization nodule formation. NCP treatment promotes osteoblastic differentiation of PDL cells; therefore, it may be beneficial for treating periodontitis.


Dissociating emotion-induced blindness and hypervision.
Previous findings suggest that emotional stimuli sometimes improve (emotion-induced hypervision) and sometimes impair (emotion-induced blindness) the visual perception of subsequent neutral stimuli. We hypothesized that these differential carryover effects might be due to 2 distinct emotional influences in visual processing. On the one hand, emotional stimuli trigger a general enhancement in the efficiency of visual processing that can carry over onto other stimuli. On the other hand, emotional stimuli benefit from a stimulus-specific enhancement in later attentional processing at the expense of competing visual stimuli. We investigated whether detrimental (blindness) and beneficial (hypervision) carryover effects of emotion in perception can be dissociated within a single experimental paradigm. In 2 experiments, we manipulated the temporal competition for attention between an emotional cue word and a subsequent neutral target word by varying cue-target interstimulus interval (ISI) and cue visibility. Interestingly, emotional cues impaired target identification at short ISIs but improved target identification when competition was diminished by either increasing ISI or reducing cue visibility, suggesting that emotional significance of stimuli can improve and impair visual performance through distinct perceptual mechanisms.


[Diagnostic value of gamma glutamyl transpeptidase and the mean corpuscular volume in chronic hepatitis of alcoholic etiology].
In order to assess the diagnostic value of serum gamma-glutamyl-transpeptidase (GGT) and mean corpuscular volume (MCV) as markers of alcoholism in chronic liver diseases, 107 patients with non-alcoholic chronic liver disease and 192 patients with alcoholic liver disèases have been compared. GGT and MCV values were checked two times: the day of admission to hospital and 10 days after complete withdrawal from alcohol. The patients with alcoholic liver diseases present significantly higher values of GGT and MCV in respect with patients with non-alcoholic liver diseases. A significant (p < 0.05) decrease of about 50% in serum GGT levels and of about 3% in MCV was observed after alcohol withdrawal only in the group of alcoholic liver diseases whereas no changes were found in the other group of patients: For the diagnosis of alcoholism in chronic liver diseases, while the sensitivity and the specificity of the several markers vary from 50% to 86%, the positive predictive values of GGT and MCV at admission were 92.2% and 73.4%, and the negative predictive values were 40.2% and 75.7%, respectively. Moreover, the positive predictive values of GGT and MCV after 10 days of alcohol withdrawal were 95.3% and 85.9% and the negative predictive values were 31.8% and 46.7%, respectively. The contemporary decrease in GGT and MCV values does not seem to offer better informations than GGT decrease. These data suggest that, even if GGT and MCV do appear per se as weak indicators of alcoholism during chronic liver diseases, the early decrease in their values, especially in serum GGT, are good and specific markers of alcohol abuse and, consequently, of the alcoholic etiology of liver disease.


Impact of post-challenge hyperglycemia on clinical outcomes in Japanese patients with stable angina undergoing percutaneous coronary intervention.
Post-challenge hyperglycemia (PH) is well-established as one of risk factors for coronary artery disease. However, it remains unclear whether PH affects clinical outcomes in patients with stable angina undergoing percutaneous coronary intervention (PCI). A total of 828 patients with stable angina undergoing PCI were retrospectively analyzed. Of these, 452 patients with previously diagnosed diabetes mellitus (DM) or fasting plasma glucose (PG) ≥126 mg/dl and HbA1c ≥6.5% were defined as known DM. The remaining 376 patients were divided into the two groups according to 2-h PG: PH (2-h PG ≥140 mg/dl, n=236) and normal glucose tolerance (NGT, 2-h PG <140 mg/dl, n=140). We assessed the rate of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, stroke, and clinically-driven revascularization. During the median follow-up of 4.3 years, the MACE rate was significantly higher in the DM and PH groups than the NGT group (39.3% vs. 20.7%, P <0.001; 31.4% vs. 20.7%, P=0.044, respectively). Compared with the NGT group, the cumulative incidence of revascularization was significantly higher in the DM group (35.1% vs. 18.5%, P <0.001) and tended to be higher in the PH group (27.1% vs. 18.5%, P=0.067). In the multivariate analysis, known DM (Hazard ratio [HR]: 2.16, 95% confidence interval (CI): 1.49-3.27, P < 0.001), PH (HR: 1.62, 95% CI: 1.07-2.53, P = 0.023), LDL-C >100 mg/dl (HR: 1.62, 95% CI: 1.26 to 2.10, P < 0.001), and previous stroke (HR: 1.47, 95% CI: 1.03-2.04, P = 0.034) were predictors of MACE. PH is associated with future cardiovascular events in patients with stable angina undergoing PCI.


Regulation of invertase levels in Avena stem segments by gibberellic Acid, sucrose, glucose, and fructose.
Gibberellic acid and sucrose play significant roles in the increases in invertase and growth in Avena stem segments. About 80% of invertase is readily solubilized, whereas the rest is in the cell wall fraction. The levels of both types of invertase change in a similar manner in the response to gibberellic acid and sucrose treatment. The work described here was carried out with only the soluble enzyme. In response to a treatment, the level of invertase activity typically follows a pattern of increase followed by decrease; the increase in activity is approximately correlated with the active growth phase, whereas the decrease in activity is initiated when growth of the segments slows. A continuous supply of gibberellic acid retards the decline of enzyme activity. When gibberellic acid was pulsed to the segments treated with or without sucrose, the level of invertase activity increased at least twice as high in the presence of sucrose as in its absence, but the lag period is longer with sucrose present. Cycloheximide treatments effectively abolish the gibberellic acid-promoted growth, and the level of enzyme activity drops rapidly. Decay of invertase activity in response to cycloheximide treatment occurs regardless of gibberellic acid or sucrose treatment or both, and it is generally faster when the inhibitor is administered at the peak of enzyme induction than when given at its rising phase. Pulses with sucrose, glucose, fructose, or glucose + fructose elevate the level of invertase significantly with a lag of about 5 to 10 hours. The increase in invertase activity elicited by a sucrose pulse is about one-third that caused by a gibberellic acid pulse given at a comparable time during mid-phase of enzyme induction, and the lag before the enzyme activity increases is nearly twice as long for sucrose as for gibberellic acid. Moreover, the gibberellic acid pulse results in about three times more growth than the sucrose pulse. Our studies support the view that gibberellic acid, as well as substrate (sucrose) and end products (glucose and fructose), play a significant role in regulating invertase levels in Avena stem tissue, and that such regulation provides a mechanism for increasing the level of soluble saccharides needed for gibberellic acid-promoted growth.


Effects of FLT3 ligand on human leukemia cells. II. Agonistic and antagonistic effects of other cytokines.
We have previously shown that the growth factor FLT3 ligand (FL) is mitogenic for human primary and continuously cultured myeloid leukemia cells. Despite widespread expression of the receptor FLT3 among the leukemia cell lines from certain cell lineages, only two growth factor-dependent myeloid leukemia cell lines showed a significant proliferative response to FL. In the present study, we examined the proliferative effects of FL on a comprehensive set of growth factor-dependent leukemia cell lines. A significant enhancement of cell growth by FL was seen in 10/12 myelomonocytic cell lines, while all cell lines with predominantly megakaryocytic and/or erythroid characteristics did not respond positively, despite the expression of the receptor. The cytokines interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) could independently enhance the FL-stimulated proliferation in a synergistic fashion. Transforming growth factor-(beta)1 (TGF-(beta)1), in a dose-dependent fashion, partially inhibited the FL-promoted proliferation, but basic fibroblast growth factor (bFGF), on its own augmenting the response to FL, significantly abrogated the inhibitory effects of TGF-(beta)1. TGF-(beta)1 down-regulated mRNA and protein expression of the FLT3 receptor. Taken together these data suggest that the effects of FL on the growth of normal and malignant hematopoietic cells can be positively and negatively modulated by other cytokines.


Role of medial prefrontal NMDA receptors in spatial delayed alternation in 19-, 26-, and 33-day-old rats.
Long-Evans rats were trained on spatial delayed alteration (SDA) in a T-maze following medial prefrontal cortical (mPFC) infusions of different doses of the noncompetitive NMDA-receptor antagonist, MK-801 (.125 microl; .25 microl; or .25 microlsaline, bilaterally), on postnatal day (PND) 19, 26, or 33. Pups trained on PND 19 showed almost no learning of SDA, regardless of drug condition (including saline). On PND 26, both doses of MK-801 significantly and equivalently prevented SDA learning, with performance during the final three training blocks remaining near chance levels, in contrast with 85% correct performance in the saline control group. On PND 33, substantial SDA learning was evident regardless of dose, although a modest impairment appeared in mid-training at both doses. These findings confirm previous reports of mPFC involvement in the early postnatal ontogeny of SDA and suggest a developmentally transient role of mPFC NMDA-receptor function in this task.


Structural characterization of novel sophorolipid biosurfactants from a newly identified species of Candida yeast.
Sophorolipids are a group of O-acylsophorose-based biosurfactants produced by several yeasts of the Starmerella clade. The known sophorolipids are typically partially acetylated 2-O-β-D-glucopyranosyl-D-glucopyranose (sophorose) O-β-glycosidically linked to 17-L-hydroxy-Δ9-octadecenoic acid, where the acyl carboxyl group often forms a 4″-lactone to the terminal glucosyl residue. In a recent MALDI-TOFMS-based screen for sophorolipid-producing yeasts we identified a new species, Candida sp. NRRL Y-27208, that produces significant amounts of novel sophorolipids. This paper describes the structural characterization of these new compounds, using carbohydrate and lipid analysis, mass spectrometry, and NMR spectroscopy. Unlike those reported previously, the NRRL Y-27208 sophorolipids contain an ω-hydroxy-linked acyl group (typically 18-hydroxy-Δ9-octadecenoate), and occur predominantly in a non-lactone, anionic form. In addition, 17 dimeric and trimeric sophoroses were identified by MALDI-TOFMS from this strain. The surfactant-like properties of these sophorolipids have value as potential replacements for petroleum-based detergents and emulsifiers.


Human cells compromised for p53 function exhibit defective global and transcription-coupled nucleotide excision repair, whereas cells compromised for pRb function are defective only in global repair.
After exposure to DNA-damaging agents, the p53 tumor suppressor protects against neoplastic transformation by inducing growth arrest and apoptosis. A series of investigations has also demonstrated that, in UV-exposed cells, p53 regulates the removal of DNA photoproducts from the genome overall (global nucleotide excision repair), but does not participate in an overlapping pathway that removes damage specifically from the transcribed strand of active genes (transcription-coupled nucleotide excision repair). Here, the highly sensitive ligation-mediated PCR was employed to quantify, at nucleotide resolution, the repair of UVB-induced cyclobutane pyrimidine dimers (CPDs) in genetically p53-deficient Li-Fraumeni skin fibroblasts, as well as in human lung fibroblasts expressing the human papillomavirus (HPV) E6 oncoprotein that functionally inactivates p53. Lung fibroblasts expressing the HPV E7 gene product, which similarly inactivates the retinoblastoma tumor-suppressor protein (pRb), were also investigated. pRb acts downstream of p53 to mediate G(1) arrest, but has no demonstrated role in DNA repair. Relative to normal cells, HPV E6-expressing lung fibroblasts and Li-Fraumeni skin fibroblasts each manifested defective CPD repair along both the transcribed and nontranscribed strands of the p53 and/or c-jun loci. HPV E7-expressing lung fibroblasts also exhibited reduced CPD removal, but only along the nontranscribed strand. Our results provide striking evidence that transcription-coupled repair, in addition to global repair, are p53-dependent in UV-exposed human fibroblasts. Moreover, the observed DNA-repair defect in HPV E7-expressing cells reveals a function for this oncoprotein in HPV-mediated carcinogenesis, and may suggest a role for pRb in global nucleotide excision repair.


Associations between environmental characteristics and life-space mobility in community-dwelling older people.
To examine the association between perceived environmental barriers to and facilitators for outdoor mobility with life-space among older people. Community-dwelling, 75- to 90-year-old people (n = 848) were interviewed face-to-face using standard questionnaires. The Life-Space Assessment (LSA), indicating distance and frequency of moving and assistance needed in moving (range 0-120), was used. Environmental barriers and facilitators outdoors were self-reported. Altogether, 41% (n = 348) of the participants had restricted life-space (LSA score < 60). Those reporting one or more environmental barriers had more than double the odds for restricted life-space compared with those reporting no barriers after adjustments for ill health, functioning, and socioeconomic status (SES) differences. Similarly, those reporting four to seven facilitators had lower odds for restricted life-space compared with those reporting three or fewer facilitators. Perceptions of one's environment may either constrain or extend older people's life-space. Longitudinal studies are needed to study the causality of the findings.


The experimental and clinical pathology of diene conjugation.
The simple spectroscopic measurement of diene conjugation has long been an established but somewhat problematic marker of free-radical activity in biological systems. The main diene-conjugated compounds in human tissues and tissue fluids have now been identified as esters of octadeca-9,11-dienoic acid (18:2(9,11)), a non-peroxide isomer of linoleic acid (18:2(9,12)); and a range of high-performance liquid chromatographic methods has been developed for their detection and measurement. Significant abnormalities of phospholipid-esterified 18:2(9,11) have been found in the serum of chronic alcoholics and in paraquat poisoning and of non-esterified 18:2(9,11) in lipolytic states. The phospholipid-esterified 18:2(9,11) is increased in the bile of patients with pancreatic disease. In exfoliated cells from the cervix uteri an abnormal molar ratio between phospholipid-esterified 18:2(9,11) and 18:2(9,12) may prove to be the most sensitive biochemical marker of precancerous change.


Convergence rate for numerical computation of the lattice Green's function.
Flexible boundary-condition methods couple an isolated defect to bulk through the bulk lattice Green's function. Direct computation of the lattice Green's function requires projecting out the singular subspace of uniform displacements and forces for the infinite lattice. We calculate the convergence rates for elastically isotropic and anisotropic cases for three different techniques: relative displacement, elastic Green's function correction, and discontinuity correction. The discontinuity correction has the most rapid convergence for the general case.


Transcriptional glucose signaling through the glucose response element is mediated by the pentose phosphate pathway.
Glucose catabolism induces the expression of the L-type pyruvate kinase (L-PK) gene through the glucose response element (GIRE). The metabolic pathway used by glucose after its phosphorylation to glucose 6-phosphate by glucokinase to induce L-PK gene expression in hepatocytes remains unknown. The sugar alcohol xylitol is metabolized to xylulose 5-phosphate, an intermediate of the nonoxidative branch of the pentose phosphate pathway. In this study, we demonstrated that xylitol at low concentration (O.5 mM) induced the expression of the L-PK/CAT construct in glucose-responsive mhAT3F hepatoma cells at the same level as 20 mM glucose, while it did not affect intracellular concentration of glucose 6-phosphate significantly. The effect of xylitol on the induction of the L-PK gene expression was noncumulative with that of glucose since 20 mM glucose plus 5 mM xylitol induced the expression of the L-PK/CAT construct similarly to 20 mM glucose alone. In hepatocytes in primary culture, 5 mM xylitol induced accumulation of the L-PK mRNA even in the absence of insulin. Furthermore, the response to xylitol as well as glucose required the presence of a functional GIRE. It can be assumed from these results that glucose induces the expression of the L-PK gene through the nonoxidative branch of the pentose phosphate pathway. The effect of xylitol at low concentration suggests that the glucose signal to the transcriptional machinery is mediated by xylulose 5-phosphate.


Productivity vs. training in primary care: analysis of hospitals and health centers in New York City.
This paper examines the indirect costs of primary care residency in terms of ambulatory care site productivity and the influence of graduate medical education (GME) subsidies on the employment of primary care residents. Using a sample of hospitals and health centers in New York City (NYC), we find that most facilities employ significantly more primary care residents relative to nonresident primary care physicians than would be dictated by cost-minimizing behavior in the production of primary care. We also find evidence that New York's GME subsidy encourages the "overemployment" of residents, while the Medicare GME subsidy does not. We conclude that the trade-off between productivity and teaching is more serious in primary care than in inpatient settings, and that facilities heavily involved in ambulatory care teaching will be at a competitive disadvantage if GME subsidies are not targeted specifically for primary care.


[Current surgery of the nasal septum].
Rhinoseptoplasty, septoplasty in particular, is among the most commonly used operations in otorhinolaryngology. So far, over a long period of time, a variety of operative procedures successful for their time have been developed. The present report deals with a total of 4700 patients, operated on over an 18-year period (1977 through 1994). Pertinent physiological and anatomical data concerning the nasal septum are briefly outlined. A number of operative methods are analyzed. Proceeding from the postoperative results, preference is given to Cottle's procedure.


What is the shape of the helium trimer? A comparison with the neon and argon trimers.
Despite its apparent simplicity and extensive theoretical investigations, the issue of what is the shape of the helium trimer is still debated in the literature. After reviewing previous conflicting interpretations of computational studies, we introduce the angle-angle distribution function as a tool to discuss in a simple way the shape of any trimer. We compute this function along with many different geometrical distributions using variational and diffusion Monte Carlo methods. We compare them with the corresponding ones for the neon and argon trimers. Our analysis shows that while Ne(3) and Ar(3) fluctuate around an equilibrium structure that is an equilateral triangle, (4)He(3) shows an extremely broad angle-angle distribution function, and all kinds of three-atom configurations must be taken into account in its description. Classifying (4)He(3) as either equilateral or linear or any other particular shape, as was done in the past, is not sensible, because in this case the intuitive notion of equilibrium structure is ill defined. Our results could help the interpretation of future experiments aimed at measuring the geometrical properties of the helium trimer.


A rapid and efficient transformation protocol for the grass Brachypodium distachyon.
A fast and efficient microprojectile bombardment-mediated transformation protocol is reported for the grass species Brachypodium distachyon, a proposed alternative model plant to Oryza sativa for functional genomics in grasses. Embryogenic calli derived from immature embryos were transformed by a construct containing the uidA (coding for beta-glucuronidase) and bar (coding for phosphinothricin acetyl transferase) genes, and bialaphos, a non-selective herbicide, was used as the selection agent throughout all phases of the tissue culture. Average transformation efficiencies of 5.3% were achieved, and for single bombardments transformation efficiencies of up to 14% were observed. The time frame from the bombardment of embryogenic callus to the harvesting of transgenic T1 seeds was 29 weeks and 25 weeks for the diploid and two tetraploid accessions used, respectively. Since the seed-to-seed life cycle is 19 weeks for the diploid and 15 weeks for the tetraploid accessions, our B. distachyon transformation system allows testing of both the T0 and the T1 generation as well as production of T2 seeds within 1 year.


Effects of various chemical sterilization methods on the crosslinking and enzymatic degradation characteristics of an epoxy-fixed biological tissue.
Due to the nature of bioprostheses, which are mainly biological tissues that cannot be sterilized with heat or irradiation, the sterilization method by choice is generally liquid chemicals. It is known that a number of liquid chemicals can have rapid germicidal effect and can be used to sterilize bioprostheses. The study was to evaluate the effects of various chemical sterilization methods on the crosslinking and enzymatic degradation characteristics of an epoxy-fixed biological tissue. The chemical sterilants employed were: a 70% ethanol solution (EtOH), a 2% epoxy compound + 20% ethanol solution (EX-810), a 2% propylene oxide + 20% ethanol solution (PO), and a 0.625% glutaraldehyde + 20% ethanol + 0.2% polysorbate solution (GA). Both masking and crosslinking of the free amino groups within the epoxy-fixed tissue were observed subsequent to sterilization with GA or EX-810. This improved the resistance of the GA or EX-810 sterilized tissues against collagenase degradation as compared to its nonsterilized counterpart. However, subsequent to sterilization with PO, only masking of the free amino groups within the epoxy-fixed tissue was noted. The inhibition of the collagenase degradation by masking of the free amino groups was traded off by the more random molecular packing of the PO sterilized sample due to the introduction of the side branches. Sterilization of the epoxy-fixed tissue with EtOH may increase its denaturation temperature and tensile strength, while neither masking nor crosslinking of free amino groups within the tissue took place. The resistance to degradation of the EtOH sterilized tissue, however, did not improve as compared to its nonsterilized counterpart.


Alcohol consumption in early adolescence and medical care.
Alcohol consumptionin adolescents is a risky behavior that can be prevented. Objective. To determine health care and alcohol consumption pattern in early adolescence and its relation to determinants of health (biological, environmental, social and health system factors). A qualitative-quantitative, crosssectional study was carried out in the four schools belonging to Popular Council 8 of Mario Gutiérrez Ardaya health sector in May, 2013. The study universe was made up of adolescents aged 10-14. The sample was determined through a simple randomized sampling. Surveys were administered to adolescents, parents, educators and senior health staff members to determine alcohol consumption, medical care quality and level of knowledge on the problem. A nominal group with health professionals was created. Two hundred and eighty eight adolescents were included. 54.5% were alcohol users, of which 30.2% were 10-11 years old. Those classified as low risk were prevailing (55.6%). 100% of the senior health staff expressed the need for a methodology of care. 90.4% of education staff considered adolescence as a vulnerable stage. Relatives reported that there should be adolescent-specific medical appointments (61.8%). The nominal group's most important opinions were based on the main features that a consultation for adolescents should have and on the problems hindering proper care. Alcohol consumption was considered high and early start prevailed. Insufficient care to early adolescents who use alcohol was made evident.


PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis.
Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA). Many studies have reported that both a 'shared epitope' (SE) encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4) gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA. JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic) and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs), rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays. Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5-11.9, pc < 0.001). No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA)-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71-23.7 pc = 0.03). PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations.


Evaluating measures of association for single-cell transcriptomics.
Single-cell transcriptomics provides an opportunity to characterize cell-type-specific transcriptional networks, intercellular signaling pathways and cellular diversity with unprecedented resolution by profiling thousands of cells in a single experiment. However, owing to the unique statistical properties of scRNA-seq data, the optimal measures of association for identifying gene-gene and cell-cell relationships from single-cell transcriptomics remain unclear. Here, we conducted a large-scale evaluation of 17 measures of association for their ability to reconstruct cellular networks, cluster cells of the same type and link cell-type-specific transcriptional programs to disease. Measures of proportionality were consistently among the best-performing methods across datasets and tasks. Our analysis provides data-driven guidance for gene and cell network analysis in single-cell transcriptomics.


The European Bioinformatics Institute (EMBL-EBI) in 2021.
The European Bioinformatics Institute (EMBL-EBI) maintains a comprehensive range of freely available and up-to-date molecular data resources, which includes over 40 resources covering every major data type in the life sciences. This year's service update for EMBL-EBI includes new resources, PGS Catalog and AlphaFold DB, and updates on existing resources, including the COVID-19 Data Platform, trRosetta and RoseTTAfold models introduced in Pfam and InterPro, and the launch of Genome Integrations with Function and Sequence by UniProt and Ensembl. Furthermore, we highlight projects through which EMBL-EBI has contributed to the development of community-driven data standards and guidelines, including the Recommended Metadata for Biological Images (REMBI), and the BioModels Reproducibility Scorecard. Training is one of EMBL-EBI's core missions and a key component of the provision of bioinformatics services to users: this year's update includes many of the improvements that have been developed to EMBL-EBI's online training offering.


Chronic Achilles Tendon Ruptures: From Bracing Treatment to Complex Reconstruction.
The optimal management of chronic Achilles tendon injuries continues to be debated. The tension-length relationship and intrinsic viscoelasticity of the native tendon that allows efficient propulsion during ambulation are difficult to restore once the tendon has been injured. Missed or misdiagnosed injuries or failure of surgical or nonsurgical management of acute Achilles tendon ruptures can lead to the tendon healing in an elongated position or lack of healing altogether. This condition results in persistent weakness, pain, and functional debilitation for the patient. Understanding the tendon and muscle properties will inform the choice of treatment. Nonsurgical treatment options are primarily bracing treatment and physical therapy. Surgical treatment options involve direct repair, reconstruction with local tissue, allograft or autograft, and tendon transfer. Various options and techniques for reconstruction are described to assist in optimizing management of this challenging clinical problem.


Influence of macrophages and macrophage-modified collagen I on the adhesion and proliferation of vascular smooth muscle cells in culture.
The adhesion, proliferation and morphology of rat vascular smooth muscle cells (VSMC) in cocultures with macrophages or in cultures on type I collagen modified by activated macrophages were evaluated. In the first set of experiments, rat alveolar macrophages were added to 24-hour-old VSMC cultures. Between days 2 and 5 after VSMC seeding, the population densities and doubling times of cells were similar in both VSMC-macrophage and pure VSMC cultures. However, from day 5, the cocultures proliferated about two times more rapidly and on day 7, they reached higher cell population density by 40%. The pure macrophage cultures did not proliferate. In the second set of experiments, rat alveolar macrophages were activated by non-toxic TiO2 dust to produce reactive oxygen species and incubated for 120 min with collagen I. The collagen was then adsorbed on plastic culture dishes and seeded with VSMC. The collagen exposed for 10 min only, the unmodified collagen and pure culture dishes were used as control growth supports. On all four tested substrates, the number of initially adhered cells was similar, but on the collagen modified for 120 min, the cells were less spread. Moreover, on day 2 to 3 after seeding, some cells on this collagen became vacuolated and detached spontaneously from the growth support. The remaining VSMC, however, rapidly proliferated, so that on day 9, the cell population density on 120-min-modified collagen was similar as on both control collagens and significantly higher compared to that on uncoated dishes. Our results suggest that 1. The delayed growth-stimulating effect of macrophages on VSMC-macrophage mixed population is probably due to autocrine production of mitogens by both cell types rather than due to an acute effect of short-living oxygen radicals released from macrophages immediately after adding to VSMC cultures. 2. The effect of collagen I exposed to activated macrophages for 120 min is slightly cytotoxic, which could, however, stimulate a release of mitogens from damaged as well as surviving VSMC.