Soft tissue sarcomas.
This synthesis of the literature on radiotherapy for sarcomas originating in the body's soft, supportive tissues, ie, muscle, connective tissue, and fatty tissue is based on 71 scientific articles, including 4 randomized studies, 5 prospective studies, and 26 retrospective studies. These studies involve 3,444 patients. Over 90% of patients with soft tissue sarcomas in the arms and legs can be treated in a way that preserves the extremities. Subcutaneous and intramuscular sarcomas can be treated surgically with little functional loss or risk for local recurrence without adjuvant radiotherapy. To avoid amputation, surgery is often combined with radiotherapy for treatment of local relapse. Adequate surgical margins are usually difficult to achieve for head/neck tumors and retroperitoneal tumors, and therefore surgery is often combined with radiotherapy to reduce the risk for local relapse. Pre- and postoperative radiotherapy are similar. A disadvantage of preoperative radiotherapy is that it reduces the opportunity for exact diagnosis and determining morphobiologic sarcoma parameters. To further improve treatment results for advanced sarcomas, it is necessary to introduce other fractionation schedules, mainly hyperfractionation. This places greater demands on radiotherapy, mainly for staff resources. Combining radiotherapy and local intraarterial chemotherapy involves greater risks for complications and has not shown better treatment results than pre- or postoperative radiotherapy alone, and it is not recommended as standard treatment for soft tissue sarcomas. Intraoperative treatment methods should be targeted for further study and development.


Rivastigmine is a potent inhibitor of acetyl- and butyrylcholinesterase in Alzheimer's plaques and tangles.
Acetylcholinesterase and butyrylcholinesterase activities emerge in association with plaques and tangles in Alzheimer's disease. These pathological cholinesterases, with altered properties, are suggested to participate in formation of plaques. The present experiment assessed the ability of rivastigmine, a clinically utilized agent that inhibits acetylcholinesterase and butyrylcholinesterase activities, to inhibit cholinesterases in plaques and tangles. Cortical sections from cases of Alzheimer's disease were processed using cholinesterase histochemistry in the presence or absence of rivastigmine. Optical densities of stained sections were utilized as a measure of inhibition. The potency of rivastigmine was compared with those of other specific inhibitors. Optimum staining for cholinesterases in neurons and axons was obtained at pH 8.0. Cholinesterases in plaques, tangles and glia were stained best at pH 6.8. Butyrylcholinesterase-positive plaques were more numerous than acetylcholinesterase-positive plaques. Rivastigmine inhibited acetylcholinesterase in all positive structures in a dose-dependent manner (10(-6)-10(-4) M). However, even at the highest concentration, faint activity remained. In contrast, rivastigmine resulted in complete inhibition of butyrylcholinesterase in all structures at 10(-5) M. Rivastigmine was equipotent to the specific acetylcholinesterase inhibitor BW284C51 and more potent than the butyrylcholinesterase inhibitors iso-OMPA and ethopropazine. In conclusion, rivastigmine is a potent inhibitor of acetylcholinesterase and a more potent inhibitor of butyrylcholinesterase in plaques and tangles. Unlike other cholinesterase inhibitors tested, rivastigmine inhibited cholinesterases in normal and pathological structures with the same potency. Thus, at the therapeutic concentrations used, rivastigmine is likely to result in inhibition of pathological cholinesterases, with the potential of interfering with the disease process.


Gatekeepers' perceptions of the quality and availability of services for breast and cervical cancer patients in the English-speaking Windward Islands: an exploratory investigation.
Although extensive screening services for breast and cervical cancers are available in the Caribbean, these cancers continue to be the leading causes of cancer death among women in this region. The purpose of this study was to determine the quality and availability of breast and cervical cancer treatment care and support services from the perspective of the gatekeepers who provide care for the patients in the Windward Islands of Dominica, Grenada, St Lucia, and St. Vincent. A qualitative research design using semi-structured, in-depth interviews was used to gather data from gatekeepers who provided oncology prevention and care services to patients for at least one year. Data were collected on availability and quality of cancer care and treatment services and coded using the themes obtained via thematic analysis of the data. Twenty-three current providers participated in the study (Dominica, 5; Grenada, 7; St. Lucia, 5; St. Vincent and the Grenadines, 6). The participants' years of work experience ranged from 2 to 45 years. The codes encompassed a range of social ecological factors that influence breast and cervical cancer screening and treatment in the Windward Islands. The emergent themes were availability of resources, cost of care, and social support. The findings of this study emphasize the varying social determinants of health that affect breast and cervical cancer prevention and treatment. It also highlights the disparities in availability of treatment within the wider Caribbean. It is necessary to broaden the perspective on health from a purely biomedical paradigm to a social perspective.


Laparoscopic gastric bypass: risks vs. benefits up to two years following surgery in super-super obese patients.
Super-super obesity (body mass index [BMI] >/= 60 kg/m(2)) is thought to be a risk factor for complications and mortality in laparoscopic Roux-en-Y gastric bypass. Excess weight loss has been demonstrated to be diminished compared with less obese patients following surgery. However, we hypothesize that super-super obese patients who undergo laparoscopic gastric bypass can realize major improvements in their health and a good quality of life without a significantly increased risk of complications when compared with less obese patients. From July 2002 to July 2005, University of Wisconsin Health bariatric surgeons performed 288 consecutive laparoscopic Roux-en-Y gastric bypass procedures. Patients were divided into 2 groups: BMI >/= 60 kg/m(2) (n = 28) and BMI < 60 kg/m(2) (n = 260). The groups were compared at defined time intervals during a 2-year period following surgery. Comparison criteria included complications, weight loss, comorbidities, and quality of life. Both groups had similar morbidity and mortality rates. Excess weight loss was shown to be less, but total pounds lost were greater, for the super-super obese patients at all postoperative time intervals specified for postoperative analysis. Despite this fact, overall health improved to a similar degree in each group of patients following surgery; both groups also had similar Moorehead-Ardelt quality of life scores. Using the Bariatric Analysis and Reporting Outcome System (BAROS) to categorize outcomes, the average result for a patient in either group of patients would be considered "very good" at 1 year following surgery. Laparoscopic Roux-en-Y gastric bypass can be accomplished safely even in extremely obese patients. Although excess weight loss in the super-super obese is diminished postoperatively when compared with less obese patients, health is improved and quality of life is good regardless of a patient's preoperative BMI. Therefore, laparoscopic gastric bypass is a good option even in the extremely obese.


Deep Sequencing of Serum Small RNAs Identifies Patterns of 5' tRNA Half and YRNA Fragment Expression Associated with Breast Cancer.
Small noncoding RNAs circulating in the blood may serve as signaling molecules because of their ability to carry out a variety of cellular functions. We have previously described tRNA- and YRNA-derived small RNAs circulating as components of larger complexes in the blood of humans and mice; the characteristics of these small RNAs imply specific processing, secretion, and physiological regulation. In this study, we have asked if changes in the serum abundance of these tRNA and YRNA fragments are associated with a diagnosis of cancer. We used deep sequencing and informatics analysis to catalog small RNAs in the sera of breast cancer cases and normal controls. 5' tRNA halves and YRNA fragments are abundant in both groups, but we found that a breast cancer diagnosis is associated with changes in levels of specific subtypes. This prompted us to look at existing sequence datasets of serum small RNAs from 42 breast cancer cases, taken at the time of diagnosis. We find significant changes in the levels of specific 5' tRNA halves and YRNA fragments associated with clinicopathologic characteristics of the cancer. Although these findings do not establish causality, they suggest that circulating 5' tRNA halves and YRNA fragments with known cellular functions may participate in breast cancer syndromes and have potential as circulating biomarkers. Larger studies with multiple types of cancer are needed to adequately evaluate their potential use for the development of noninvasive cancer screening.


Potential of hypocotyl diameter in family selection aiming at plant architecture improvement of common bean.
Cultivars of common bean with more erect plant architecture and greater tolerance to degree of lodging are required by producers. Thus, to evaluate the potential of hypocotyl diameter (HD) in family selection for plant architecture improvement of common bean, the HDs of 32 F2 plants were measured in 3 distinct populations, and the characteristics related to plant architecture were analyzed in their progenies. Ninety-six F2:3 families and 4 controls were evaluated in a randomized block design, with 3 replications, analyzing plant architecture grade, HD, and grain yield during the winter 2010 and drought 2011 seasons. We found that the correlation between the HD of F2 plants and traits related to plant architecture of F2:3 progenies were of low magnitude compared to the estimates for correlations considering the parents, indicating a high environmental influence on HD in bean plants. There was a predominance of additive genetic effects on the determination of hypocotyl diameter, which showed higher precision and accuracy compared to plant architecture grade. Thus, this characteristic can be used to select progenies in plant architecture improvement of common beans; however, selection must be based on the means of at least 39 plants in the plot, according to the results of repeatability analysis.


Coverage and precision of confidence intervals for area under the curve using parametric and non-parametric methods in a toxicokinetic experimental design.
The coverage and precision of parametric Bailer-type confidence intervals (CIs) for area under the curve (AUC) was compared to nonparametric bootstrap confidence intervals. Concentration-time data was simulated using Monte Carlo simulation under a toxicokinetic paradigm with sparse (SSC) and dense sampling (DSC) conditions. AUC was calculated using the trapezoidal rule and 95% CIs were computed using various parametric and nonparametric methods. Under SSC, the various parametric CIs contained the true population AUC with coverage probabilities ranging from 0.77 to 0.95 with low inter-subject variation (coefficient of variation (CV) = 15%) and from 0.82 to 0.95 with high inter-subject variation (CV = 50%). The nominal value should be close to 0.95. DSC tended to increase coverage by about 0.05. Bailer's method always produced the lowest coverage of all parametric CIs examined. Under SSC, bootstrap CIs had coverage probabilities ranging from 0.62 (CV = 15%) to 0.68 (CV = 50%). DSC increased coverage to 0.77. Parametric CIs were wider than their nonparametric counterparts, often giving lower CI estimates less than zero. Bailer's method and Bailer's method using the jackknife estimate of the standard error were the worst in this respect. Bootstrap CIs never had lower CI estimates less than zero. However, SSC tends to produce bootstrap distributions that are not continuous which, if used, may produce biased CI estimates. Bootstrap CI estimates were judged to be the "best". However, the limitations of the bootstrap should be clearly recognized and it should not be used indiscriminately. Examination of the bootstrap distribution for its degree of discreteness must be part of the statistical process.


A novel role of cannabinoids: implication in the fever induced by bacterial lipopolysaccharide.
There is continuing interest in elucidating the actions of drugs of abuse on the immune system and on infection. The present study investigated the effects of the cannabinoid (CB) receptor agonist aminoalkylindole, (+)-WIN 55,212-2 [(4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], on fever produced after injection of lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, the best known and most frequently used experimental model. Intraperitoneal injection of LPS (50 mug/kg) induced a biphasic fever, with the first peak at 180 min and the second at 300 min postinjection. Pretreatment with a nonhypothermic dose of the cannabinoid receptor agonist WIN 55,212-2 (0.5-1.5 mg/kg i.p.) antagonized the LPS-induced fever. However, pretreatment with the inactive enantiomer WIN 55,212-3 [1.5 mg/kg i.p.; S-(-)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthanlenyl)methanone mesylate] did not. The inhibitory effect of WIN 55,212-2 on LPS-induced fever was reversed by SR141716 [N-(piperdin-1-yl)-5-(4-chloropheny)-1-(2,4-dichloropheny)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride], a selective CB1 receptor antagonist, but not by SR144528 (N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]5-(4-choro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide), a selective antagonist at the CB2 receptor. The present results show that cannabinoids interact with systemic bacterial LPS injection and indicate a role of the CB1 receptor subtype in the pathogenesis of LPS fever.


Metabolomic analysis identifies the regulation of lipid metabolism pathway as potential mechanisms of Jiangzhi decoction against non-alcoholic fatty liver disease.
To illustrate the metabolic regulatory mechanisms of Jiangzhi decoction (JZD) against non-alcoholic fatty liver disease (NAFLD). High-fat diet (HFD)-induced NAFLD rats were treated with JZD. The pathological morphology, lipid indexes and liver function were detected. Metabolic profiles were examined by liquid chromatography-mass spectrometry (LC-MS). Multivariate and univariate statistical analysis were used to search the differential metabolites. Pathway enrichment analysis was carried out using Kyoto Encyclopedia of Genes and Genomes database. Compound-gene networks were built by Cytoscape software. JZD significantly alleviated the pathological conditions and improved lipid index levels. Multivariate analysis showed a good separation among different groups. Three hundred and twenty-seven metabolites in HFD versus control and 301 metabolites in JZD versus HFD were identified to be significantly different. Pathway enrichment analysis showed that lipid metabolism pathways were prominent altered pathways. Importantly, the relationships were more distant between JZD and HFD groups in all five lipid metabolism pathways, including arachidonic acid metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism and sphingolipid metabolism, while those were obviously closer between JZD and control groups. Simultaneously, JZD treatment restored the levels of disturbed differential metabolites in HFD group. JZD had an effect on alleviating NAFLD via regulating relevant lipid metabolism.


An alternative approach for statistical analysis of kidney transplant data: multivariate analysis of single-center experience.
To avoid the center effect and the possible hidden interactions of multicenter studies, the validity of the Cox Proportional Hazards Model for the analysis of a single-center kidney transplant program was tested, considering 287 renal transplants performed in a 10-year period. The inclusion of type of donor and main immunosuppressive drug as covariates in the model did not violate the proportionality assumption of the Cox model. According to this method, the following covariates were significant in predicting graft survival: cyclosporine, type of donor, good human leukocyte antigen (HLA)-A and HLA-B match (DR data were not considered), highest percentage of reactive antibodies against panel cells, and nephroangiosclerosis as a primary renal disease. Cyclosporine did not significantly improve graft survival in living related donor transplants. Pretransplant blood transfusions, cold ischemia time, and donor ABO blood group were initially significant but dropped out in the step-down procedure. Recipient's age at transplant, cyclosporine, HLA-A and HLA-B match, and nephroangiosclerosis were significant in predicting patient survival. It was concluded that using long-term data of cadaveric and living related renal transplants either on azathioprine or cyclosporine is a valid way to perform multivariate analysis of single-center transplant programs that do not have large samples.


Cardiotonic steroids stabilize regulator of G protein signaling 2 protein levels.
Regulator of G protein signaling 2 (RGS2), a G(q)-specific GTPase-activating protein, is strongly implicated in cardiovascular function. RGS2(-/-) mice are hypertensive and prone to heart failure, and several rare human mutations that accelerate RGS2 degradation have been identified among patients with hypertension. Therefore, pharmacological up-regulation of RGS2 protein levels might be beneficial. We used a β-galactosidase complementation method to screen several thousand compounds with known pharmacological functions for those that increased RGS2 protein levels. Several cardiotonic steroids (CTSs), including ouabain and digoxin, increased RGS2 but not RGS4 protein levels. CTSs increased RGS2 protein levels through a post-transcriptional mechanism, by slowing protein degradation. RGS2 mRNA levels in primary vascular smooth muscle cells were unaffected by CTS treatment, whereas protein levels were increased 2- to 3-fold. Na(+)/K(+)-ATPase was required for the increase in RGS2 protein levels, because the effect was lost in Na(+)/K(+)-ATPase-knockdown cells. Furthermore, we demonstrated that CTS-induced increases in RGS2 levels were functional and reduced receptor-stimulated, G(q)-dependent, extracellular signal-regulated kinase phosphorylation. Finally, we showed that in vivo treatment with digoxin led to increased RGS2 protein levels in heart and kidney. CTS-induced increases in RGS2 protein levels and function might modify several deleterious mechanisms in hypertension and heart failure. This novel CTS mechanism might contribute to the beneficial actions of low-dose digoxin treatment in heart failure. Our results support the concept of small-molecule modulation of RGS2 protein levels as a new strategy for cardiovascular therapy.


Small bowel metastases from primary carcinoma of the lung.
Although about half of all patients with carcinoma of the lung have metastases at initial presentation, only nine with metastases to the small bowel have been previously reported. This study was performed to determine the incidence of occult and clinically apparent metastases of lung cancer to the small intestine. Small bowel metastases were present in 46 of 431 patients with primary lung cancer who underwent autopsy during an 11-year period. These patients had an average of 4.8 metastatic sites. Small bowel metastases were present in 12 of 31 (39.0%) patients with large cell carcinoma, 13 of 108 (12.3%) with adenocarcinoma, six of 73 (8.0%) with small cell carcinoma, 15 of 199 (7.5%) with squamous cell carcinoma, and none of 20 with undifferentiated carcinoma. During the same interval, six of 78 patients undergoing small bowel resection for metastatic tumor had lung cancer primaries. Among the nine previously reported clinical cases of small bowel metastases and the six in this series, 14 were operated upon for small bowel perforation and one for obstruction. Nine patients died perioperatively, and no patient survived longer than 16 weeks. These data demonstrate that the incidence of lung cancer metastases to the small bowel is higher than is clinically apparent. Lung cancer metastases to the small bowel often present as intestinal perforation and indicate a poor prognosis; surgery is indicated for palliation.


Scabiosa Genus: A Rich Source of Bioactive Metabolites.
The genus Scabiosa (family Caprifoliaceae) is considered large (618 scientific plant names of species) although only 62 have accepted Latin binominal names. The majority of the Scabiosa species are widely distributed in the Mediterranean region and some Scabiosa species are used in traditional medicine systems. For instance, Scabiosa columbaria L. is used traditionally against diphtheria while S. comosa Fisch. Ex Roem. and Schult. is used in Mongolian and Tibetan traditional medical settings to treat liver diseases. The richness of Scabiosa species in secondary metabolites such as iridoids, flavonoids and pentacyclic triterpenoids may contribute to its use in folk medicine. Details on the most recent and relevant pharmacological in vivo studies on the bioactive secondary metabolites isolated from Scabiosa species will be summarized and thoroughly discussed.


Twelve years of rabies surveillance in Sri Lanka, 1999-2010.
Rabies is endemic in Sri Lanka, but little is known about the temporal and spatial trends of rabies in this country. Knowing these trends may provide insight into past control efforts and serve as the basis for future control measures. In this study, we analyzed distribution of rabies in humans and animals over a period of 12 years in Sri Lanka. Accumulated data from 1999 through 2010 compiled by the Department of Rabies Diagnosis and Research, Medical Research Institute (MRI), Colombo, were used in this study. The yearly mean percentage of rabies-positive sample was 62.4% (47.6-75.9%). Three-fourths of the rabies-positive samples were from the Colombo, Gampaha, and Kalutara districts in Western province, followed by Galle in Southern province. A high percentage of the rabies samples were from dogs (85.2%), followed by cats (7.9%), humans (3.8%), wild animals (2.0%), and livestock (1.1%). Among wild animals, mongooses were the main victims followed by civets. The number of suspect human rabies cases decreased gradually in Sri Lanka, although the number of human samples submitted for laboratory confirmation increased. The number of rabid dogs has remained relatively unchanged, but the number of suspect human rabies is decreasing gradually in Sri Lanka. These findings indicate successful use of postexposure prophylaxis (PEP) by animal bite victims and increased rabies awareness. PEP is free of charge and is supplied through government hospitals by the Ministry of Health, Sri Lanka. Our survey shows that most positive samples were received from Western and Southern provinces, possibly because of the ease of transporting samples to the laboratory. Submissions of wild animal and livestock samples should be increased by creating more awareness among the public. Better rabies surveillance will require introduction of molecular methods for detection and the establishment of more regional rabies diagnostic laboratories.


Rapid identification of chemical constituents of Rhodiola crenulata using liquid chromatography-mass spectrometry pseudotargeted analysis.
Rhodiola crenulata (R. crenulata), is a famous traditional Chinese medicine, with observable effects such as anti-high-altitude illness and fatigue resistance. Nevertheless, comprehensive and systematic structural identification of its components remains a challenge. In this study, a pseudotargeted analytical method, involving key fragment filtering by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and ultra-high performance liquid chromatography-linear ion trap-Orbitrap mass spectrometry, was developed for rapid detection and identification of the chemical constituents of R. crenulata. The process consists of three steps: (i) acquiring sufficient mass spectral data, (ii) constructing a key fragments schedule and discovering the substructures rapidly by pseudotargeted key fragment filtering, and (iii) further identification of the compound structures based on accurate masses, fragment ions, related literatures, and authentic standards. As a result, 104 compounds were identified and divided into five categories, among which three potentially new and 59 ones were reported for the first time in R. crenulata. These results indicated that the major types of components are flavanols and gallic acid derivatives, organic acids, alcohols and their glycosides, flavonoids and their glycosides. This study enhances the understanding of R. crenulata and provides a reference for rapid and comprehensive identification of constituents in other herbal medicines.


Daratumumab-mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti-KIR antibody IPH2102 and lenalidomide.
Despite recent treatment improvements, multiple myeloma remains an incurable disease. Since antibody-dependent cell-mediated cytotoxicity is an important effector mechanism of daratumumab, we explored the possibility of improving daratumumab-mediated cell-mediated cytotoxicity by blocking natural killer cell inhibitory receptors with the human monoclonal anti-KIR antibody IPH2102, next to activation of natural killer cells with the immune modulatory drug lenalidomide. In 4-hour antibody-dependent cell-mediated cytotoxicity assays, IPH2102 did not induce lysis of multiple myeloma cell lines, but it did significantly augment daratumumab-induced myeloma cell lysis. Also in an ex vivo setting, IPH2102 synergistically improved daratumumab-dependent lysis of primary myeloma cells in bone marrow mononuclear cells (n=21), especially in patients carrying the FcγRIIIa-158F allele or the FcγRIIa-131R allele, who bind IgG1 with lower affinity than patients carrying the FcγRIIIa-158V allele or the FcγRIIa-131H allele. Finally, a further synergistically improved myeloma cell lysis with the daratumumab-IPH2102 combination was observed by adding lenalidomide, which suggests that more effective treatment strategies can be designed for multiple myeloma by combining daratumumab with agents that independently modulate natural killer cell function.


Patients who are candidates for subacromial decompression have more pronounced range of motion deficits, but do not differ in self-reported shoulder function, strength or pain compared to non-candidates.
Subacromial impingement syndrome (SIS) is associated with low self-reported shoulder function, impairments in shoulder strength and range of motion (ROM), and pain. It is not known how the symptomatology associated with SIS is reflected in the choice of treatment. This study compares self-reported shoulder function, shoulder strength, ROM, and pain in patients with SIS considered candidates and non-candidates for subacromial decompression (SAD). Self-reported shoulder function (Q-DASH and SPADI), maximum isometric muscle strength in shoulder abduction (Abd-strength) and external rotation (ER-strength), active abduction ROM (Abd-ROM) and passive internal rotation ROM (IR-ROM) were measured in a consecutive cohort of patients with SIS referred to an orthopedic outpatient clinic. Additionally, pain during each test and pain levels during the last week were reported. Patients were categorized as candidates or non-candidates for SAD based on their consultation with an orthopedic specialist blinded to test results and self-reported shoulder function. All outcomes and age, gender, weight and duration of symptoms were compared using the unpaired t test or Mann-Whitney's U test as appropriate. One-hundred and fifty-seven patients were included. 25 patients were candidates for SAD, while 132 were not. SAD candidates had significantly lower Abd-ROM (87° vs. 112°, p = 0.011, effect size = 0. 15) and IR-ROM (114° vs. 123°, p = 0.026, effect size = 0.58) additional to higher pain during test of Abd-strength (5.3 vs. 3.7, p = 0.02, effect size = 0.21). No other differences were found between the groups. A decrease in abduction and internal rotation range of motion, and increased pain during maximal abduction strength effort are associated with being considered a candidate for subacromial decompression, while self-reported shoulder function, pain during the last week, and rotator cuff strength are not. As SAD candidates primarily differentiates from non-candidates by having more pronounced ROM deficits, it might be important to address ROM in pre- and postsurgical evaluations, but as the overall differences between the two groups seem minor, the relation between impairments and the choice of treatment needs further clarification. IV.


The Potential of Systems Biology to Discover Antibacterial Mechanisms of Plant Phenolics.
Drug resistance of bacterial pathogens is a growing problem that can be addressed through the discovery of compounds with novel mechanisms of antibacterial activity. Natural products, including plant phenolic compounds, are one source of diverse chemical structures that could inhibit bacteria through novel mechanisms. However, evaluating novel antibacterial mechanisms of action can be difficult and is uncommon in assessments of plant phenolic compounds. With systems biology approaches, though, antibacterial mechanisms can be assessed without the bias of target-directed bioassays to enable the discovery of novel mechanism(s) of action against drug resistant microorganisms. This review article summarizes the current knowledge of antibacterial mechanisms of action of plant phenolic compounds and discusses relevant methodology.


A laboratory and clinical evaluation of an immunochemiluminometric assay of thyrotropin in serum.
We evaluated an immunochemiluminometric assay for human thyrotropin. A chemiluminescent acridinium ester is used as a label, with magnetic-particle separation. The lower limit of detection of the assay (mean + 3 SD of the zero standard) was 0.07 milli-int. unit/L, with a working range of 0.5 to greater than 60.0 milli-int. units/L. Assay accuracy was good as judged from analytical recovery, analysis of external quality-assessment samples, and comparison with an enzyme-amplified immunoassay. There were no significant interferences or cross-reactivities. Twenty-four samples assayed showed aggregation of the magnetic particles. On re-assay, four of these samples showed a significant increase in the measured TSH by the luminescence assay. Assay time for 60 tubes was approximately 3.5 h with the use of a semi-automated luminometer. The reference interval, determined from data on 144 healthy euthyroid subjects, was 0.3-4.0 milli-int. units/L. Sixteen of 19 thyrotoxic patients showed clearly suppressed concentrations of thyrotropin in serum.


Penile Livedoid Vasculopathy: First Reported Case.
Livedoid vasculopathy is a thromboocclusive cutaneous vasculopathy manifested by livedoid changes, atrophie blanche, and ulceration. The pathogenesis is speculated to involve increasing coagulation or impaired thrombolysis leading to the occlusion of dermal blood vessels with fibrin thrombi. Livedoid vasculopathy is known to primarily affect the lower extremities. We report the first case of livedoid vasculopathy affecting the penis. A 60-year-old male was evaluated for a split urine stream with associated irritation and peeling of the skin of the glans penis. His penile ulcer continued to enlarge despite steroids and antibiotics. Due to diagnostic uncertainty, a biopsy was performed which revealed hyaline thrombi within the lumens of small vessels within the upper to mid dermis, fibrinoid material in the walls of these blood vessels and within the perivascular stroma with overlying and adjacent epidermal spongiosis, and mild perivascular lymphocytic infiltrate with a few scattered neutrophils most consistent with livedoid vasculitis. He was started on aspirin and pentoxifylline with limited improvement and was later started on apixaban with near-complete resolution in 6 months. Penile livedoid vasculopathy has not been previously reported in the English literature. Early diagnosis and treatment are imperative to limit morbidity.


Developing Consensus on Priority Pediatric Otolaryngology-Head and Neck Surgery Conditions and Procedures.
The aim of this study was to develop an international expert consensus on priority pediatric otolaryngology-head and neck surgery (OHNS) conditions and procedures for which all national health systems globally should be capable of managing. The Delphi method is a multiround online questionnaire and was administered internationally to otolaryngologists with a focus on pediatric populations. This study was administered in parallel to a Delphi survey focusing on adult OHNS conditions amongst adult otolaryngology experts. International online survey. In round 1, participants listed the top 15 pediatric otolaryngological conditions and top 15 pediatric otolaryngology procedures for their World Bank region. In round 2, participants ranked round 1 responses in order of global importance on a 5-point Likert scale. In round 3, participants reranked conditions and procedures that did not achieve consensus, defined as at least 70% of the round 2 Likert responses being ranked as either "important" or "very important." Descriptive statistics were calculated for each round. The survey was distributed to 35 experts globally, with a 40% (n = 14) response rate. Fifty percent (n = 7) of participants were from low- and middle-income countries, with at least 1 participant from each World Bank region. A list of 28 consensus surgical procedures and 11 consensus conditions were identified. This Delphi survey method of world experts in pediatric otolaryngology identified a core list of medical conditions and surgical procedures that should be a part of every national health system's clinical goals of treatment, research, and capacity building.


Distinct roles of NMDA receptors at different stages of granule cell development in the adult brain.
NMDA receptor (NMDAR)-dependent forms of synaptic plasticity are thought to underlie the assembly of developing neuronal circuits and to play a crucial role in learning and memory. It remains unclear how NMDAR might contribute to the wiring of adult-born granule cells (GCs). Here we demonstrate that nascent GCs lacking NMDARs but rescued from apoptosis by overexpressing the pro-survival protein Bcl2 were deficient in spine formation. Insufficient spinogenesis might be a general cause of cell death restricted within the NMDAR-dependent critical time window for GC survival. NMDAR loss also led to enhanced mushroom spine formation and synaptic AMPAR activity throughout the development of newborn GCs. Moreover, similar elevated synapse maturation in the absence of NMDARs was observed in neonate-generated GCs and CA1 pyramidal neurons. Together, these data suggest that NMDAR operates as a molecular monitor for controlling the activity-dependent establishment and maturation rate of synaptic connections between newborn neurons and others.


"Yes they have the right to know, but…": Young Adult Women Managing Private Health Information as Dependents.
This study explored how young adult women manage privacy regarding their health information as dependents on a parent's insurance policy. Under current and proposed health care reform in the United States, young adults between the ages of 18 and 26 years can remain on a parent's policy as a dependent, which can improve young adult's access to health care services. Although dependent expansion provisions can improve coverage for young adults, it may also threaten their privacy by giving a parent access to adult-child's private health information. Using Communication Privacy Management, this study investigated how dependent young adult women conceptualize and negotiate information ownership with parents in a forced disclosure situation. Results revealed young adult women either felt they alone should own and control their health information or believed a parent as the policy hold should have access to the information. However, all preferred to be in control of the disclosure and used core and catalyst criteria to manage the privacy dilemma current health care policy creates. Specifically, the threat of a parent seeing an adult-child used a stigmatized health service motivated young adult women to engage in deception, pay out of pocket for services covered by insurance, and put off or avoid health care. Results of this study complicate assumptions about privacy management and demonstrate how health care policy affects family communication.


Effect of intramuscular and intravenous lidocaine on propofol induction dose.
Our purpose was to study whether or not intravenous (IV) administration of lidocaine reduces propofol dose requirement as intramuscular (IM) lidocaine in a placebo-controlled manner. Seventy-five adult patients with American Society of Anesthesiologists physical status I and II, aged 20-60 years who were scheduled for surgery under general anaesthesia were included in the study. The patients were randomly allocated to 3 groups: IM: intramuscular administration; IV: intravenous administration and C: control. There were 25 patients in each group. The patients in group IM received lidocaine 1.5 mg · kg(-1) administered into the deltoid muscle 10 min before anaesthesia induction. In group IV, the patients received IV lidocaine 1.5 mg · kg(-1), 2 min before anaesthesia induction. Group C patients served as control group who received only propofol injection. Hypnosis after propofol administration was measured with response to verbal commands. There were no statistical differences between group IM (100.8 ± 26.1 mg) and group IV (110.8 ± 30.1 mg) regarding the induction dose of propofol (p > 0.05). In group C, the required propofol dose (151.2 ± 27.4 mg) for anaesthesia induction was significantly higher than in the other groups (p < 0.001). No side effect was observed in any patients. In this study, both IV and IM lidocaine administration were effective in reducing the hypnotic dose of propofol without any side effects. In addition, IV lidocaine may be more comfortable for awake patients.


The Role of Galectin-3 in Predicting Congenital Heart Disease Outcome: A Review of the Literature.
Galectin-3 (Gal-3) is a novel pro-fibrotic biomarker that can predict both right and left cardiac dysfunction caused by various cardiovascular conditions. Its expression seems to be progressively altered with evolving cardiac remodeling processes, even before the onset of heart failure. Hence, Gal-3 has been found to be an individual predictor of acute and chronic heart failure or to serve as part of an integrated biomarker panel that can foresee adverse cardiac outcomes. In congenital heart disease (CHD), Gal-3 correlates with cardiac mortality and complications in both children and adults and is proposed as a therapeutic target in order to reverse the activation of pro-fibrosis pathways that lead to heart failure. Positive associations between serum Gal-3 levels, post-operatory hospitalization rates, complications and ventricular dysfunction have also been reported within studies conducted on patients with CHD who underwent corrective surgery. Thus, this review tried to address the potential utility of Gal-3 in patients with CHD and particularly in those who undergo corrective surgery. The heterogeneity of the literature data and the lack of validation of the results obtained by the current studies on larger cohorts cannot be neglected, though. Further longitudinal research is required to establish how Gal-3 can relate to long-term outcomes in pediatric CHD.


EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis.
To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research.


Safety and efficacy of topical norfloxacin versus tobramycin in the treatment of external ocular infections.
Bacterial conjunctivitis appears to resolve more rapidly when treated with appropriate topical antimicrobial agents. In this multicenter, randomized, double-blind study of efficacy and safety, patients with presumed bacterial external eye infections were assigned to topical therapy with 0.3% norfloxacin or 0.3% tobramycin. A total of 120 patients were enrolled. Of the total, 65 had documented bacterial infections and were evaluable; 59 of these patients had bacterial conjunctivitis. All of the patients with documented infections were cured or improved regardless of the drug treatment regimen or in vitro susceptibility testing results. The most common bacteria isolated were Haemophilus influenzae, Streptococcus pneumoniae, alpha-hemolytic streptococci, Staphylococcus aureus, and Staphylococcus sp. No patients had serious adverse reactions attributed to their therapy. Norfloxacin ophthalmic solution seems to be a safe, effective, and appropriate agent for the treatment of bacterial external eye infections.


Adrenocorticotropin- and opiate-like hormones from pituitaries of the sockeye salmon Oncorhynchus nerka.
The pituitaries of vitellogenic sockeye salmon (Oncorhynchus nerka) were extracted with a mixture of acetone, water, and hydrochloric acid. The precipitate which formed upon the addition of a copious volume of acetone to the extract, designated acid acetone powder, was subjected to salt fractionation and desalting, followed by ion-exchange chromatography on CM-cellulose. An unadsorbed fraction (S-1) and four adsorbed fractions (S-2, S-3, S-4 and S-5) were obtained. Adrenocorticotropic activity was detected in the fractions by their ability to stimulate isolated rat adrenal decapsular cells to produce corticosterone and by their immunoreactivities in an adrenocorticotropin-specific radioimmunoassay. The steroidogenic activities of all fractions, except S-4, were blocked by corticotropin inhibiting peptide. Opiate activity was detected in the fractions by their ability to inhibit the binding of either [3H]naloxone or (D-ala2, D-leu5)-[3H]enkephalin to rat brain membranes. There was a discrepancy in the potencies of the five fractions in the two opiate radioreceptor assays, indicating the presence of opiate peptides with different affinities of binding to the micron- and delta-opiate receptors of the rat brain. There was a separation between adrenocorticotropic and opiate receptor binding activities, suggesting that the activities were due to separate molecular entities.


Effect of clathrate hydrate formation and decomposition on NMR parameters in THF-D2O solution.
The NMR spin-lattice relaxation time (T(1)), spin-spin relaxation time (T(2)) and the diffusion coefficient D were measured for (1)H in a 1:17 mol % solution of tetrahydrofuran (THF) in D(2)O. The aim of the work was to clarify some earlier points raised regarding the utility of these measurements to convey structural information on hydrate formation and reformation. A number of irregularities in T(1) and T(2) measurements during hydrate processes reported earlier are explained in terms of the presence of interfaces and possible temperature gradients. We observe that T(1) and T(2) in solution are exactly the same before and after hydrate formation, thus confirming that the solution is isotropic. This is inconsistent with the presence of memory effects, at least those that may affect the dynamics to which T(1) and T(2) are sensitive. The measurement of the diffusion coefficient for a number of hours in the subcooled solution before nucleation proved invariant with time, again suggesting that the solution remains isotropic without affecting the guest dynamics and diffusion.


Interrogating a clinical database to study treatment of hypotension in the critically ill.
In intensive care, it is imperative to resolve hypotensive episodes (HEs) in a timely manner to minimise end-organ damage. Clinical practice guidelines generally recommend initial treatment with fluid resuscitation followed by vasoactive agent administration if patients remain hypotensive. However, the impact of such interventions on patient outcomes has not been clearly established. Hence, the objective of this study was to investigate the relationship between fluid and vasoactive agent interventions and patient outcomes, while highlighting the utility of electronic medical records in clinical research. Retrospective cohort study. Intensive care units (ICUs) at a large, academic, tertiary medical center. Patients in Multi-parameter Intelligent Monitoring in Intensive Care II (a large electronic ICU database) who experienced a single HE during their ICU stay. 2332 patients had complete data. The primary outcome of interest was inhospital mortality. Secondary outcomes were ICU length of stay (LOS), HE duration, Hypotension Severity Index (defined as the mean arterial pressure curve area below 60 mm Hg during the HE) and rise in serum creatinine. Fluid resuscitation was associated with significantly shorter ICU LOS among ICU survivors (p=0.007). Vasoactive agent administration significantly decreased HE duration (p<0.001) and Hypotension Severity Index (p=0.002) but was associated with increased inhospital mortality risk (p<0.001), prolonged ICU LOS among ICU survivors (p=0.04) and rise in serum creatinine (p=0.002) after adjustment for confounders. Propensity score analyses as well as sensitivity analyses in treatment-, diagnosis- and ICU service-specific subpopulations corroborated the relationship between vasoactive agents and increased inhospital mortality. An adverse relationship between vasoactive agents and inhospital mortality was found in patients with hypotension. This study has implications for the care of critically ill patients with hypotension and illustrates the utility of electronic medical records in research when randomised controlled trials are difficult to conduct.


K:Cl cotransport: emerging molecular aspects of a ouabain-resistant, volume-responsive transport system in red blood cells.
Erythrocytes from teleosts to mammals, like man, possess a ouabain-resistant K flux component which is Cl-dependent and activated upon suspension of the cells into hyposmotic media. This volume-responsive K:Cl cotransporter may be synonymous with a Cl-dependent K pathway stimulated by chemical interventions such as SH group (thiol) alkylation or oxidation at cytoplasmic sites of the membrane. Based on a comparison of the response of the two activity expressions of probably the same molecule to ionic and metabolic perturbations a molecular model is proposed accommodating K:Cl flux activities under a variety of stimulatory and inhibitory influences. Physiologically, this pathway may be involved in the maturational cell volume reduction occurring between the stages of reticulocytes and the final erythrocytes as well as corresponsible for the expression of the low K steady state of certain animal red blood cells. The pathophysiological potential of this K:Cl transporter lies in the fact that, when activated, red blood cells dehydrate through K:Cl loss.


Relation of maternal zinc nutriture to pregnancy outcome and infant development in an Egyptian village.
Zinc nutriture of women living in a periurban Egyptian village was examined over the last 6 mo of pregnancy and the first 6 mo of lactation as one of several potential determinants of pregnancy outcome and infant development. Estimated bioavailable zinc intake was approximately 2 mg/d from diets high in phytate and fiber. Among numerous variables analyzed by multiple regression, early pregnancy weight (3 mo) and plasma zinc concentrations in the second trimester formed the best predictor model of birth weight, accounting for 39% of the variance. Bioavailable zinc intake during pregnancy was part of a profile of micronutrient intakes related to neonatal habituation behavior, a measure of early information processing. Performance on the Bayley motor test at 6 mo of age was negatively related to maternal intakes of plant zinc, phytate, and fiber, suggesting that zinc bioavailability was involved. Maternal dietary intake explained most of the variance observed in infant motor performance; however, predictive variance was amplified by the psychosocial context.


[Influence of proteomics technology to Chinese medical science and the Chinese medicine].
Proteomics technology may study the function, organization, diversity and dynamic variety of whole cell or even whole tissue simultaneously. It has much comparability with the holistic theory of traditional Chinese medical science. Therefore, the comprehensive use of proteomics technology has significant effect on studying of pattern and pharmacology of Chinese medicine, and it will offer a brand-new chance for development of Chinese herbal medicine.


[Sex determination by discriminant analysis of calcaneal measurements on the lateral digital radiography].
Five measurements of the calcaneus taken on digital radiography (DR) of adults of Han Population of Sichuan Province were selected to determine sex by multivariate discriminant analysis. Lateral radiographs of calcaneus taken from 393 subjects were collected. The samples were randomly divided into the experimental group (148 males and 186 females) and the examined group (26 males and 33 females). Five measurements were taken from the radiography. The analysis of variance (AVON) was carried out to determine if there was significant difference between the male and female. The discriminant functions were drawn by Fisher discriminant analysis. The effects of all obtained functions were evaluated with the examined samples. There was statistically significant difference in the five measurements between the males and the females (P<0.05). Six groups of discriminant functions were obtained with an accuracy ranged from 78.4% to 88.9%. When applied on the examined samples, the sex discriminant accuracy varied from 79.7% to 86.4%. These five measurements acquired from the lateral radiographs of calcaneus could be used for sex assessment during forensic identification of individuals.


Microtubule-associated proteins, phosphorylation gradients, and the establishment of neuronal polarity.
Axonogenesis is the earliest step in acquisition of neuronal polarity. The subcellular mechanisms underlying this pivotal event are unknown. Because of the abundant presence and functional necessity of microtubule-associated proteins in growing neurites, a large effort has been directed at characterizing their role in establishment and maintenance of neuronal polarity. One unsolved puzzle is how MAPs, most of which are unpolarized in early stages of development, can locally influence microdifferentiation of axons and dendrites. In this review, we discuss recent evidence suggesting that locally controlled phosphorylation of microtubule-associated proteins tau and MAP1B may play a role in establishment of polarity and early axonal outgrowth.


Multiple drug resistance and genetic characterization of Salmonella typhimurium isolated at Chandigarh.
A total of 1072 strains of S. typhimurium were isolated in Chandigarh during 1985-1988. Genetic characterization of 'R' plasmids was attempted in 21 multiple drug resistant strains (ACKSSu TT p-19, ACKSSu, TP-I, AKSSu Tp-1). All the 21 strains were sensitive to gentamicin, furoxone and nalidixic acid. Level of resistance to different antimicrobial drugs varied from 200 to 1000 mg/L. Majority of the strains were untypable by the present set of 31 typing phages (Ut-17, Phage type 21-2, Phase type 99-2). All the plasmids belonged to class I transfer system. All the plasmids restricted some or all the typing phages of S. typhimurium and 39 also restricted phage phi 2. These plasmids belonged to F1me or I1 incompatibility groups and did not inhibit the function of fertility factor (fi-).


[Balo concentric sclerosis. Report of one case].
We report a 50 years old woman admitted to the hospital due to progressive dysphagia and disarthria of there weeks duration. On admission a right hemiparesis was noted. CSF examination showed a protein of 9 mg/dl and no cells. A brain CAT scan showed rounded bilateral subcortical frontoparietal hypodense zones peripheral contrast material enhancement. Pseudobulbar palsies and hemiparesis worsened and the patient required nasoenteral feeding. She was discharged after four months, with severe disabilities, with the diagnosis of Balo concentric, a progressive demyelinating disease.


Myristoylated alanine-rich C kinase substrate (MARCKS) is involved in myoblast fusion through its regulation by protein kinase Calpha and calpain proteolytic cleavage.
MARCKS (myristoylated alanine-rich C kinase substrate) is a major cytoskeletal protein substrate of PKC (protein kinase C) whose cellular functions are still unclear. However numerous studies have implicated MARCKS in the stabilization of cytoskeletal structures during cell differentiation. The present study was performed to investigate the potential role of Ca(2+)-dependent proteinases (calpains) during myogenesis via proteolysis of MARCKS. It was first demonstrated that MARCKS is a calpain substrate in vitro. Then, the subcellular expression of MARCKS was examined during the myogenesis process. Under such conditions, there was a significant decrease in MARCKS expression associated with the appearance of a 55 kDa proteolytic fragment at the time of intense fusion. The addition of calpastatin peptide, a specific calpain inhibitor, induced a significant decrease in the appearance of this fragment. Interestingly, MARCKS proteolysis was dependent of its phosphorylation by the conventional PKCalpha. Finally, ectopic expression of MARCKS significantly decreased the myoblast fusion process, while reduced expression of the protein with antisense oligonucleotides increased the fusion. Altogether, these data demonstrate that MARCKS proteolysis is necessary for the fusion of myoblasts and that cleavage of the protein by calpains is involved in this regulation.


Inverse bremsstrahlung and temperature relaxation in moderately coupled two-temperature plasmas.
The balance equation for the energy in moderately coupled two-temperature plasmas, in the presence of an external radiation field, is derived and analyzed. The analysis is based on the Singwi-Tosi-Land-Sjolander closure assumption. The different terms in the derived equation are identified as the rate of collisional energy absorption from the external field (inverse bremsstrahlung), and the rate of energy transfer between the electrons and the ions in the presence of the radiation field (relaxation). It is shown how these terms, which have a structurally similar appearance, reduce to known expressions for relaxation and inverse bremsstrahlung in the appropriate limits. It is found that, relative to the known expressions, electron-ion correlation tends to enhance the rates of re1axation and of the inverse bremsstrahlung process.


Change of Femoral Anteversion Angle in Children With Intoeing Gait Measured by Three-Dimensional Computed Tomography Reconstruction: One-Year Follow-Up Study.
To evaluate femoral anteversion angle (FAA) change in children with intoeing gait depending on age, gender, and initial FAA using three-dimensional computed tomography (3D-CT). The 3D-CT data acquired between 2006 and 2016 were retrospectively reviewed. Children 4 to 10 years of age with symptomatic intoeing gait with follow-up interval of at least 1 year without active treatment were enrolled. Subjects were divided into three groups based on age: group 1 (≥4 and <6 years), group 2 (≥6 and <8 years), and group 3 (≥8 and <10 years). Initial and follow-up FAAs were measured using 3D-CT. Mean changes in FAAs were calculated and compared. A total of 200 lower limbs of 100 children (48 males and 52 females, mean age of 6.1±1.6 years) were included. The mean follow-up period was 18.0±5.4 months. Average initial and follow-up FAA in children with intoeing gait was 31.1°±7.8° and 28.9°±8.2°, respectively. The initial FAA of group 1 was largest (33.5°±7.7°). Follow-up FAA of group 1 was significantly reduced to 28.7°±9.2° (p=0.000). FAA changes in groups 1, 2, and 3 were -6.5°±5.8°, -6.4°±5.1°, and -5.3°±4.0°, respectively. These changes of FAA were not significantly (p=0.355) different among the three age groups. However, FAA changes were higher (p=0.012) in females than those in males. In addition, FAA changes showed difference depending on initial FAA. When initial FAA was smaller than 30°, mean FAA change was -5.6°±4.9°. When initial FAA was more than 30°, mean FAA change was -6.8°±5.4° (p=0.019). FAA initial in children with intoeing gait was the greatest in age group 1 (4-6 years). This group also showed significant FAA decrease at follow-up. FAA changes were greater when the child was a female, younger, and had greater initial FAA.


Association of a TNAP haplotype with ankylosing spondylitis.
To use a candidate gene approach to the identification of genetic markers that are significantly associated with ankylosing spondylitis (AS). We genotyped 201 multiplex AS families with 1 exonic and 5 intronic single-nucleotide polymorphisms (SNPs) in TNAP, the gene that encodes tissue-nonspecific alkaline phosphatase, and performed family-based association analyses. In our cohort of 201 multiplex AS families, the TNAP haplotype rs3767155 (G)/rs3738099 (G)/rs1780329 (T) was significantly associated with AS (P = 0.032 by additive model). Haplotype-Based Association Testing (HBAT) analyses of AS families in which both men and women were affected showed that the same TNAP haplotype was significantly associated with AS (P = 0.002 by additive model). Using setafftrait code 1 0 0 in the HBAT program, testing specifically for affected men in AS families containing affected individuals of both sexes, this TNAP haplotype was also significantly associated with AS (P = 0.001 by additive model). The HBAT -p option (haplotype permutation test) was used to compute the "exact" P value via a Monte Carlo method for each haplotype (haplotype permutation test) and for the minimum observed P value among the haplotypes (whole marker permutation using the minimal P test), and both P values were statistically significant (2-sided P value for haplotype rs3767155 [G]/rs3738099 [G]/rs1780329 [T] = 0.00059, the smallest observed P value among all the individual haplotype scores = 0.003). Interestingly, this haplotype was not associated with AS in affected women from the same families. Our results indicate that the TNAP haplotype rs3767155 (G)/rs3738099 (G)/rs1780329 (T) is a novel genetic marker in men that is significantly associated with AS in multiplex families containing affected individuals of both sexes.


Budapest Student Health Behavior Survey--Budapest, Hungary, 1999. Findings on unintentional and intentional injuries, alcohol use, and sexual activity.
In Hungary, a large proportion of adult morbidity and mortality can be attributed to health risk behaviors that begin in early adolescence. To date, studies examining health risk behaviors among youth have rarely been undertaken in Hungary. In order to expand current research in this area, the Hungarian Metropolitan Institute of State Public Health and Public Health Officer Service and the Office on Smoking and Health at the U.S. Centers for Disease Control and Prevention developed and implemented the Budapest Student Health Behavior Survey. The objective of this study was to examine health behavior risk factors among secondary school students in Budapest in 1999. The 1999 Budapest Student Health Behavior Survey is cross-sectional school-based survey A 2-stage cluster sampling design was used to produce a representative sample of secondary students in grades 9-12 in Budapest. Information was collected on unintentional and intentional injuries, alcohol use, and sexual activity. During the 30 days preceding the survey, 28.7% of students had rarely or never worn a seatbelt and 68.1% drunk alcohol. During the 12 months preceding the survey, 14.5% had been threatened or injured with a weapon, 12.9% experienced dating violence, and 13.5% seriously considered suicide. Of the 44.7% of students who had had sexual intercourse, 29.5% had > or = 4 sex partners. Of sexually active students, 50.4% had not used a condom at last sexual intercourse. Many secondary school students in Budapest practice behaviors that place them at risk for serious health problems both in the short and long-term. Programs and policies that adequately address such behaviors among secondary school students are needed to reduce subsequent morbidity and mortality.


The autonomous regulation system functional reserves evaluation in 7-day head down bedrest.
The heart rate variability estimation was used for autonomous regulation diagnostic in the 7-day head down bedrest experiment (HDBR). The new device "Pneumocard" and the fix respirations test were applied. The growth of sympathetic activity of autonomous nervous system and reduction of functional reserves of regulation mechanisms were observed in the microgravity modeling by HDBR. The analysis of the individual data had shown, that at two volunteers with most significant growth of SI after the experiment the orthostatic intolerance was observed. The data received in experiment confirm a hypothesis that growth of sympathetic activity in microgravity is accompanied by reduction of regulation mechanisms functional reserves is prognostic unfavorable.


A dietary intervention trial for nutritional management of cardiovascular risk factors.
A multicenter clinical trial was performed in 560 patients to assess the effectiveness of a prepackaged diet plan compared with self-selected American Heart Association Step 1 and Step 2 diets in lowering risk factors for cardiovascular disease in patients with mild to moderate disease. The results of the 10-week intervention study indicate that diets meeting the current recommendations for healthful diets significantly lower biochemical risk factors for cardiovascular diseases. Although the prepackaged dietary program achieved greater patient compliance in meeting dietary goals in the free-living condition compared with the self-selected diet, the long-term outpatient compliance with these diets needs further study. It is also unclear what role prepackage diets will play in the overall dietary management of patients at risk for cardiovascular disease.


PD134308, a selective antagonist of cholecystokinin type B receptor, enhances the analgesic effect of morphine and synergistically interacts with intrathecal galanin to depress spinal nociceptive reflexes.
The effects of systemic PD134308 [0.1-3 mg/kg; an antagonist of the cholecystokinin (CCK) type B receptor], morphine, and intrathecal (i.t.) galanin (GAL) on the excitability of the spinal nociceptive flexor reflex and in the hot plate test were examined in rats. PD134308 caused a weak naloxone-reversible depression of the flexor reflex and a moderate antinociceptive effect in the hot plate test. However, PD134308 significantly potentiated the antinociceptive effect of morphine as well as its depressive effect on the flexor reflex. PD134308 and i.t. GAL synergistically depressed the flexor reflex, an effect that was reversed by naloxone. Finally, the magnitude and duration of the depression of the flexor reflex by morphine were synergistically increased by coadministering PD134308 and GAL i.t. The results demonstrated that a CCK antagonist directed to the central CCK type B receptor potentiates the analgesic effects of opioids and nonopioid drugs at the spinal level, thus supporting the notion that CCK in the central nervous system may be an endogenous, physiological opioid antagonist.


[Identification of the genome of a picornavirus isolate using Random-PCR].
To identify the genome of an enterovirus isolate (XJ90). The double-stranded cDNA of isolated virus was synthesized with anchored-random primer and was amplified with anchor primer; the PCR products were cloned into pGEM-T vector for sequencing and analysis. Analysis on agarose gel electrophoresis of the Random-PCR products showed a typical smear; 11 randomly selected clones were all homologous to the members of enteroviruses and the homology rate over 80%; the 11 clones were distributed evenly along the whole genome and they assembled 4 contigs totally 2 261 bp long which covered 30% of the genome. The homology of the fourth contig and coxsackie virus B6 was 97.3% at amino acids level. The virus gene was specifically amplified with primers derived from the sequenced clones. The picornavirus isolate XJ90 is a member of enteroviruses.


Agalsidase alfa--a preparation for enzyme replacement therapy in Anderson-Fabry disease.
Anderson-Fabry disease is an X-linked multisystemic disorder caused by a genetic deficiency of the lysosomal enzyme a-galactosidase A. The enzyme is responsible for degradation of glycolipids inside the lysosomes. Lack of catalytic activity leads to progressive depositions of undegraded glycolipids in a large number of organs. Crises of severe pain in the extremities (acroparesthesias), hypohidrosis, corneal opacities and dysfunction of several organs (kidney, brain, heart) are the leading symptoms in patients with Anderson-Fabry disease. Females may have the same symptoms as males but to a more variable degree. The variable manifestations seen in heterozygotes can be explained by the Lyon hypothesis. This hypothesis predicts that in X-linked diseases, the carriers are a mosaic of normal and mutant cells in varying proportions and hence have variable expression. As in Gaucher's disease, enzyme replacement therapy recently became available for Anderson-Fabry disease. Two drugs have gained approval in the EU by the European Agency for the Evaluation of Medicinal Products. These are agalsidase beta (Fabrazyme, Genzyme Corporation) and agalsidase alfa (Replagal, Transkaryotic Therapies, Inc.). This review will describe clinical efficacy, safety and tolerability of agalsidase alfa.


A new treatment for tinea versicolor using econazole nitrate 1.0 percent cream once a day.
Econazole nitrate 1.0 percent cream was compared with placebo for safety and efficacy in the treatment of 126 patients with tinea versicolor. Overall results showed that 97 percent of the patients who were treated with econazole nitrate 1.0 percent cream once a day achieved excellent or partial responses, while 62 percent of those patients applying the placebo cream attained similar responses. This difference is statistically significant (p = 0.001). The study results show that econazole nitrate cream is a valuable drug for the treatment of tinea versicolor.


Gap maps and intrinsic diffraction losses in one-dimensional photonic crystal slabs.
A theoretical study of photonic bands for one-dimensional (1D) lattices embedded in planar waveguides with strong refractive index contrast is presented. The approach relies on expanding the electromagnetic field on the basis of guided modes of an effective waveguide, and on treating the coupling to radiative modes by perturbation theory. Photonic mode dispersion, gap maps, and intrinsic diffraction losses of quasi guided modes are calculated for the case of self-standing membranes as well as for silicon-on-insulator structures. Photonic band gaps in a waveguide are found to depend strongly on the core thickness and on polarization, so that the gaps for transverse electric and transverse magnetic modes most often do not overlap. Radiative losses of quasiguided modes above the light line depend in a nontrivial way on structure parameters, mode index, and wave vector. The results of this study may be useful for the design of integrated 1D photonic structures with low radiative losses.


Draft Genome Sequence of Listeria monocytogenes Serovar 1/2a Strain IZSAM_Lm_14-16064, Isolated from an Italian Cooked Ham in 2014.
In this report, the draft genome sequence of Listeria monocytogenes serovar 1/2a strain IZSAM_Lm_14-16064, isolated in Italy from a cooked ham, is announced. The genome is similar to that of a clinical strain isolated in 2014.


Exhaled nitric oxide predicts exercise-induced bronchoconstriction in asthmatic school children.
Exercise-induced bronchoconstriction (EIB) is of particular importance in children with asthma. It is an important measure of asthma control and should be monitored by exercise testing. However, exercise testing puts a large demand on health-care resources and is therefore not widely used in routine monitoring of pediatric asthma control. The fractional concentration of exhaled nitric oxide (FeNO) also reflects uncontrolled asthma. We hypothesized that FeNO may be used for prescreening of asthmatic children to exclude those with good asthma control unlikely to have EIB, thereby reducing the need for exercise testing. The aim of this study was to estimate the value of FeNO as a predictor of EIB in asthmatic children. Stable outpatient asthmatic school children performed standard exercise challenge tests and measurement of FeNO. FeNO and response to a standardized submaximal exercise test on the treadmill were measured in 111 school children with asthma. EIB could be excluded with a probability of 90% in asthmatic children with FeNO levels < 20 parts per billion (ppb) without current inhaled corticosteroid treatment, and < 12 ppb in children with current inhaled corticosteroid treatment. Measurement of FeNO is a simple, and time- and resource-efficient tool that may be used to screen for EIB testing and therefore optimizes the resources for exercise testing in pediatric asthma monitoring.


Emerging Inter-Swarm Collaboration for Surveillance Using Pheromones and Evolutionary Techniques.
In this article, we propose a new mobility model, called Attractor Based Inter-Swarm collaborationS (ABISS), for improving the surveillance of restricted areas performed by unmanned autonomous vehicles. This approach uses different types of vehicles which explore an area of interest following unpredictable trajectories based on chaotic solutions of dynamic systems. Collaborations between vehicles are meant to cover some regions of the area which are unreachable by members of one swarm, e.g., unmanned ground vehicles on water surface, by using members of another swarm, e.g., unmanned aerial vehicles. Experimental results demonstrate that collaboration is not only possible but also emerges as part of the configurations calculated by a specially designed and parameterised evolutionary algorithm. Experiments were conducted on 12 different case studies including 30 scenarios each, observing an improvement in the total covered area up to 11%, when comparing ABISS with a non-collaborative approach.


Splenocyte Infusion and Whole-Body Irradiation for Induction of Peripheral Tolerance in Porcine Lung Transplantation: Modifications of the Preconditioning Regime for Improved Clinical Feasibility.
Preoperative low-dose whole-body irradiation (IRR) with 1.5 and 7 Gy thymic IRR of the recipient, combined with a perioperative donor splenocyte infusion lead to reliable donor specific peripheral tolerance in our allogeneic porcine lung transplantation model. To reduce the toxicity of this preconditioning regime, modifications of the IRR protocol and their impact on allograft survival were assessed. Left-sided single lung transplantation from major histocompatibility complex and sex mismatched donors was performed in 14 adult female minipigs. Recipient animals were exposed to 3 different protocols of nonmyeloablative IRR within 12 hours before transplantation. All animals were administered a donor splenocyte infusion on the day of lung transplantation. Intravenous pharmacologic immunosuppression was withdrawn after 28 postoperative days. Allograft survival was monitored by chest radiographs and bronchoscopy. IRR prolonged transplant survival in a dose- and field-dependent manner. Shielding of the bone marrow from IRR (total lymphoid IRR at 1.5 and 7 Gy thymic IRR) significantly reduced protocol toxicity defined as thrombocytopenia and consecutive increased bleeding propensity, but had a less effective impact on graft survival. Whole-body IRR at 0.5 and 7 Gy thymic IRR proved to be ineffective for reliable tolerance induction. Eventually, high levels of circulating CD4+CD25high regulatory T cells were present in long-term survivors. These data show that the infusion of donor-specific alloantigen in combination with IRR is efficient once a threshold dose is exceeded.


Dynamics of ionic liquid mediated quantised charging of monolayer-protected clusters.
We present the first kinetic study of quantised double layer charging of monolayer-protected gold clusters in an ionic liquid. Cyclic voltammetry and electrochemical impedance measurements reveal that kinetic control is involved in the quantised cluster charging in these room temperature melts. The level of kinetic control varies up to one order of magnitude depending on ionic liquid composition, which may have implications for the development of future nanoelectronic devices. By studying the quantised charging process in the chemically relevant permutations of two anions and two cations, we find strong indications that the ionic liquid behaviour is not a linear combination of its composing ions' properties, but is dominated by specific interactions. Based on a Walden plot analysis, we hypothesise that the chemical availability of ions is different in the various liquids, and explains the differences in monolayer-protected gold cluster (MPC) charging rates.


Does FXIII deficiency impair wound healing after myocardial infarction?
Inadequate healing of myocardial infarction may contribute to local expansion of the infarct, frequently leading to chamber dilation, heart failure, or myocardial rupture. Experimental evidence in mouse models suggests that Factor XIII might play a key role in wound healing, and low persistent values lead to increased incidence of cardiac rupture following myocardial infarction. Here we would like to share our initial clinical experiences with strikingly similar observations in patients with this grave disease, and compare these observations to experimental findings.


A Scientometric Visualization Analysis for Natural Products on Cancer Research from 2008 to 2020.
Background: An increasing number of studies have shown that natural products have anti-tumor effects, and it has become a hotspot in cancer research. However, few bibliometric analyses have been examined in this field systematically. The current study aimed to explore the status and provide the developing trends in the natural products on cancer research. Methods: Publications on natural products in cancer research were extracted from the Web of Science core collection database. CiteSpace (5.6.R3) software and GraphPad prism 6 were used to analyze and plot the references. Results: On February 1, 2021, 34,611 records of natural products in cancer research published from 2008 to 2020 were collected. The United States was the driving force, with a strong academic reputation in this area. The top-contributing institution was the Chinese Academy of Sciences. Most publications were published in Molecules. Efferth Thomas was the most prolific author, while Newman DJ was the most cited and frequently co-cited author. Flavonoid, curcumin, and polyphenol were the most widely studied natural products. Oleanolic acid and rosmarinic acid have gradually become research hotspots recently. Breast cancer, prostate cancer, and colorectal cancer were the most common types of cancer in this field. "Natural killer cell" was the leading research hotspot. The keywords of "leaf extract," "molecular docking" and "gold nanoparticle" appeared most recently as research frontiers. Conclusion: Our results provided a general overview of the major research directions of natural products research in cancer. The mechanisms of natural products, especially those related to molecular docking, gold nanoparticle, gut microbiota, and immune checkpoints may soon become hotspots and should be closely monitored.


Reduction of Radiation Exposure by Modifying Imaging Manner and Fluoroscopic Settings during Percutaneous Pedicle Screw Insertion.
Percutaneous pedicle screw (PPS) fixation is a needle based procedure that requires fluoroscopic image guidance. Consequently, radiation exposure is inevitable for patients, surgeons, and operation room staff. We hypothesize that reducing the production of radiation emission will result in reduced radiation exposure for everyone in the operation room. Research was performed to evaluate reduction of radiation exposure by modifying imaging manner and mode of radiation source. A total of 170 patients (680 screws) who underwent fusion surgery with PPS fixation from September 2019 to March 2020 were analyzed in this study. Personal dosimeters (Polimaster Ltd.) were worn at the collar outside a lead apron to measure radiation exposure. Patients were assigned to four groups based on imaging manner of fluoroscopy and radiation modification (pulse mode with reduced dose) : continuous use without radiation modification (group 1, n=34), intermittent use without radiation modification (group 2, n=54), continuous use with radiation modification (group 3, n=26), and intermittent use with radiation modification (group 4, n=56). Post hoc Tukey Honest significant difference test was used for individual comparisons of radiation exposure/screw and fluoroscopic time/screw. The average radiation exposure/screw was 71.45±45.75 μSv/screw for group 1, 18.77±11.51 μSv/screw for group 2, 19.58±7.00 μSv/screw for group 3, and 4.26±2.89 μSv/screw for group 4. By changing imaging manner from continuous multiple shot to intermittent single shot, 73.7% radiation reduction was achieved in the no radiation modification groups (groups 1, 2), and 78.2% radiation reduction was achieved in the radiation modification groups (groups 3, 4). Radiation source modification from continuous mode with standard dose to pulse mode with reduced dose resulted in 72.6% radiation reduction in continuous imaging groups (groups 1, 3) and 77.3% radiation reduction in intermittent imaging groups (groups 2, 4). The average radiation exposure/screw was reduced 94.1% by changing imaging manner and modifying radiation source from continuous imaging with standard fluoroscopy setting (group 1) to intermittent imaging with modified fluoroscopy setting (group 4). A total of 680 screws were reviewed postoperatively, and 99.3% (675) were evaluated as pedicle breach grade 0 (<2 mm). The average radiation exposure/screw for a spinal surgeon can be reduced 94.1% by changing imaging manner and modifying radiation source from real-time imaging with standard dose to intermittent imaging with modified dose. These modifications can be instantly applied to any procedure using fluoroscopic guidance and may reduce the overall radiation exposure of spine surgeons.


To Stent or Not to Stent: A Tale of Two Occlusions.
Stenting and balloon angioplasty, along with mechanical thrombectomy, have gained notability as adjunctive treatment options to intravenous tissue plasminogen activator (IV-tPA) for tandem internal carotid artery (ICA) and middle cerebral artery (MCA) occlusions (TIM occlusions). Acute ischemic strokes (AISs) secondary to TIM occlusions are associated with poor patient outcomes primarily due to low recanalization rates following intravenous thrombolysis, consequently prompting the need for more invasive recanalization efforts. Often, the treatment algorithm is based on the success of the initial angioplasty, suspected volume of completed infarction, and whether or not thrombolytics are utilized. Here, we present two patients with AIS due to TIM occlusions where two different treatment modalities were implemented for recanalization efforts. Patient 1 did not receive IV-tPA and was successfully managed with balloon angioplasty and subsequent carotid stenting followed by direct oral anticoagulant (DOAC) administration. Patient 2 received IV-tPA and balloon angioplasty without carotid stenting followed by intracranial mechanical thrombectomy. Complete recanalization was attained in both cases. Administration of IV-tPA can make subsequent carotid stenting a potentially higher-risk treatment option for patients with TIM due to potential hemorrhagic complications in the setting of requisite antiplatelet agents. Each case of AIS resulting from a TIM must be considered unique, and the use of IV thrombolytics, balloon angioplasty, carotid stenting, and mechanical thrombectomy alone or in combination must be tailored to the individual clinical parameters.


Translational research in oncology--10 years of progress and future prospects.
International efforts to sequence the genomes of various human cancers have been broadly deployed in drug discovery programmes. Diagnostic tests that predict the value of the molecularly targeted anticancer agents used in such programmes are conceived and validated in parallel with new small-molecule treatments and immunotherapies. This approach has been aided by better preclinical cancer models; an enhanced appreciation of the complex interactions that exist between tumour cells and their microenvironment; the elucidation of interactions between many of the genetic drivers of cancer, including oncogenes and tumour suppressors; and recent insights into the genetic heterogeneity of human tumours made possible by extraordinary improvements in DNA-sequencing techniques. These advances are being employed in the first generation of genomic clinical trials that will examine the feasibility of matching a broad range of systemic therapies to specific molecular tumour characteristics. More-extensive molecular characterization of tumours and their supporting matrices are anticipated to become standard aspects of oncological practice, permitting continuous molecular re-evaluations of human malignancies on a patient-by-patient and treatment-by-treatment basis. We review selected developments in translational cancer biology, diagnostics, and therapeutics that have occurred over the past decade and offer our thoughts on future prospects for the next few years.


Multiresolution graph transformers and wavelet positional encoding for learning long-range and hierarchical structures.
Contemporary graph learning algorithms are not well-suited for large molecules since they do not consider the hierarchical interactions among the atoms, which are essential to determining the molecular properties of macromolecules. In this work, we propose Multiresolution Graph Transformers (MGT), the first graph transformer architecture that can learn to represent large molecules at multiple scales. MGT can learn to produce representations for the atoms and group them into meaningful functional groups or repeating units. We also introduce Wavelet Positional Encoding (WavePE), a new positional encoding method that can guarantee localization in both spectral and spatial domains. Our proposed model achieves competitive results on three macromolecule datasets consisting of polymers, peptides, and protein-ligand complexes, along with one drug-like molecule dataset. Significantly, our model outperforms other state-of-the-art methods and achieves chemical accuracy in estimating molecular properties (e.g., highest occupied molecular orbital, lowest unoccupied molecular orbital, and their gap) calculated by Density Functional Theory in the polymers dataset. Furthermore, the visualizations, including clustering results on macromolecules and low-dimensional spaces of their representations, demonstrate the capability of our methodology in learning to represent long-range and hierarchical structures. Our PyTorch implementation is publicly available at https://github.com/HySonLab/Multires-Graph-Transformer.


Differences in body compositions, growth and food intakes between mice which have been selected for a small and large body size.
1. Q-strain mice selected for high (QLF) or low (QSC) body-weight at 6 weeks of age were compared with respect to their body-weight increases, gross body compositions and food intakes. 2. DNA, RNA, protein and hydroxyproline contents were measured. 3. QLF animals were larger at all stages of development but ate more food and gained more body-weight per unit food intake with an apparently improved efficiency of utilization compared with QSC mice. 4. The efficiency of deposition of dietary energy in Q-strain mice was found to be significantly lower than that of other growing mammals receiving similar energy intakes. 5. Body water, protein and fat of both strains were similar at birth and at 42 d of age but the contribution of fat to body-weight in the preweaning phase was greater for QLF while QSC accreted more fat per unit weight gain in the postweaning period. 6. An increase in cell number made a greater contribution to the growth post partum of the QLF mice, but by 42 d of age little difference between the number of cells per unit weight in the two strains was evident. 7. Despite increases in RNA concentrations at all stages of development, of QLF mice compared with QSC, measurements of body composition do not indicate any accompanying increases of protein concentration in these animals.


Metabolic Factors that Contribute to Lupus Pathogenesis.
Systemic lupus erythematosus (SLE) is an autoimmune disease in which organ damage is mediated by pathogenic autoantibodies directed against nucleic acids and protein complexes. Studies in SLE patients and in mouse models of lupus have implicated virtually every cell type in the immune system in the induction or amplification of the autoimmune response as well as the promotion of an inflammatory environment that aggravates tissue injury. Here, we review the contribution of CD4+ T cells, B cells, and myeloid cells to lupus pathogenesis and then discuss alterations in the metabolism of these cells that may contribute to disease, given the recent advances in the field of immunometabolism.


Amino acid sequence of the alpha subunit and computer modelling of the alpha and beta subunits of echicetin from the venom of Echis carinatus (saw-scaled viper).
Echicetin, a heterodimeric protein from the venom of Echis carinatus, binds to platelet glycoprotein Ib (GPIb) and so inhibits platelet aggregation or agglutination induced by various platelet agonists acting via GPIb. The amino acid sequence of the beta subunit of echicetin has been reported and found to belong to the recently identified snake venom subclass of the C-type lectin protein family. Echicetin alpha and beta subunits were purified. N-terminal sequence analysis provided direct evidence that the protein purified was echicetin. The paper presents the complete amino acid sequence of the alpha subunit and computer models of the alpha and beta subunits. The sequence of alpha echicetin is highly similar to the alpha and beta chains of various heterodimeric and homodimeric C-type lectins. Neither of the fully reduced and alkylated alpha or beta subunits of echicetin inhibited the platelet agglutination induced by von Willebrand factor-ristocetin or alpha-thrombin. Earlier reports about the inhibitory activity of reduced and alkylated echicetin beta subunit might have been due to partial reduction of the protein.


A Sustainable Multicomponent Pyrimidine Synthesis.
Since alcohols are accessible from indigestible biomass (lignocellulose), the development of novel preferentially catalytic reactions in which alcohols are converted into important classes of fine chemicals is a central topic of sustainable synthesis. Multicomponent reactions are especially attractive in organic chemistry as they allow the synthesis of large libraries of diversely functionalized products in a short time when run in a combinatorial fashion. Herein, we report a novel, regioselective, iridium-catalyzed multicomponent synthesis of pyrimidines from amidines and up to three (different) alcohols. This reaction proceeds via a sequence of condensation and dehydrogenation steps which give rise to selective C-C and C-N bond formations. While the condensation steps deoxygenate the alcohol components, the dehydrogenations lead to aromatization. Two equiv of hydrogen and water are liberated in the course of the reactions. PN5P-Ir-pincer complexes, recently developed in our laboratory, catalyze this sustainable multicomponent process most efficiently. A total of 38 different pyrimidines were synthesized in isolated yields of up to 93%. Strong points of the new protocol are its regioselectivity and thus the immediate access to pyrimidines that are highly and unsymmetrically decorated with alkyl or aryl substituents. The combination of this novel protocol with established methods for converting alcohols to nitriles now allows to selectively assemble pyrimidines from four alcohol building blocks and 2 equiv of ammonia.


Screening nursing students to identify those at high risk of poor mental health: a cross-sectional survey.
This study aimed to identify those at high risk of poor mental health among nursing students and to examine the relationships and consistency among five mental health assessments. A cross-sectional design with purposive sampling was used. Four mental health screening tools plus previous mental health history/information were conducted during June 2015 to October 2016. A nursing major university in Taiwan. A total of 2779 participants aged between 19 and 45 years were recruited. Five mental health risks were identified: increased risk for ultra-high risk, putative prepsychosis states, high trait anxiety, high state anxiety with genetic risk and depression. Out of the 3395 collected questionnaire, 2779 (82%) were found valid and included in the study. 612 (22%) of the participants were identified to be at mental health risk. 12 of them appeared positive in four, 79 in three, 148 in two and 373 in one of the adopted mental health screening tools. 69 participants had the experience of seeking medical help due to mental health issues, and 58% of them were identified to be at risk of mental health during the screening. Trait and state anxiety scored the highest in correlation analysis (r(2620)=0.76, p<0.001). Correlations were observed in the scores on the subscales of Chinese Version of Schizotypal Personality Questionnaire-Brief (CSPQ-B) and those of Brief self-report Questionnaire for Screening Putative Prepsychotic States (BQSPS), and the highest correlation coefficients was (r(2740)=0.70, p<0.001). Although both of the screening tools are used to assess mental illness risk at its prodromal phase, but CSPQ-B in general appeared to have more rigorous screening criteria than BQSPS. For expediting early identification high risk of poor mental health, easy-to-use screening questionnaires can be adopted to assess the mental health state of nursing students whose mental well-being and overall health are of vital importance to the entire healthcare industry.


Efficacy of monensin against turkey coccidiosis in laboratory and floor-pen experiments.
Monensin at 60, 80, or 100 ppm in feed reduced mortality and lesion scores while protecting against weight loss of turkeys infected with the major pathogenic species: Eimeria adenoides, E. meleagrimitis, and E. gallopavonis. With single and mixed infections in battery-cage experiments, the death rate of unmedicated turkey poults was 33-75%. Weight gains were significantly (P is less than or equal to 0.05) better with 100 ppm monensin than 60 ppm, as were also lesion scores. Under floor-pen conditions there were no significant differences among monensin treatments. Moisture content of the litter was significantly lower in all monensin-medicated pens (40%, compared with 52% moisture in pens of unmedicated controls).


Transition to blended learning: experiences from the first year of our blended learning Bachelor of Nursing Studies programme.
The School of Nursing at Dublin City University offered a new blended learning Bachelor of Nursing Studies programme in the academic year 2011. To document the experiences of the academic team making the transition from a face-to-face classroom-delivered programme to the new blended learning format. Academics who delivered the programme were asked to describe their experiences of developing the new programme via two focus groups. Five dominant themes were identified: Staff Readiness; Student Readiness; Programme Delivery and Student Engagement; Assessment of Module Learning Outcomes and Feedback; and Reflecting on the First Year and Thinking of the Future. Face-to-face tutorials were identified as very important to both academics and students. Reservations about whether migrating the programme to an online format encouraged students to engage in additional practices of plagiarism were expressed by some. Student ability/readiness to engage with technology-enhanced learning was an important determinant of their own success academically. In the field of nursing blended learning is a relatively new and emerging field which will require huge cultural shifts for staff and students alike.


Correction of joint angles from Kinect for balance exercising and assessment.
The new generation of videogame interfaces such as Microsoft's Kinect opens the possibility of implementing exercise programs for physical training, and of evaluating and reducing the risks of elderly people falling. However, applications such as these might require measurements of joint kinematics that are more robust and accurate than the standard output given by the available middleware. This article presents a method based on particle filters for calculating joint angles from the positions of the anatomical points detected by PrimeSense's NITE software. The application of this method to the measurement of lower limb kinematics reduced the error by one order of magnitude, to less than 10°, except for hip axial rotation, and it was advantageous over inverse kinematic analysis, in ensuring a robust and smooth solution without singularities, when the limbs are out-stretched and anatomical landmarks are aligned.


Temperature-induced dynamical conformational disorder in 4-vinyl benzoic acid molecular crystals: a molecular simulation study.
Extensive molecular simulations are carried out as a function of temperature to understand and quantify the conformational disorder in molecular crystals of 4-vinyl benzoic acid. The conformational disorder is found to be dynamic and associated with a flip-flop motion of vinyl groups. The population of minor conformer is less than 3% up to 300 K and is 13.2% at 350 K and these results are consistent with the experimental observations. At still higher temperatures, the population of minor conformer increases up to 25%. The evolution of structure at both molecular and unit-cell level of the molecular crystal as a function of temperature has been characterized by various quantities such as radial distribution functions, average cell parameters, volume, and interaction energies. The van't Hoff plot shows a nonlinear behavior at lower temperatures as it has been reported recently by Ogawa and co-workers in the case of stilbene, azobenzene, and N-(4-methylbenzylidene)-4-methylaniline molecular crystals. A set of rigid body simulations were also carried out to quantify the effect of conformational disorder on structural quantities such as unit-cell volume and interaction energy. The anomalous shrinkage of vinyl C=C bond length as a function of temperature has been explained by combining the results of simulations and a set of constrained optimizations using ab initio electronic structure calculations for various molecular structures differing in torsional angle.


Rapid calculation of diffuse reflectance from a multilayered model by combination of the white Monte Carlo and adding-doubling methods.
To rapidly derive a result for diffuse reflectance from a multilayered model that is equivalent to that of a Monte-Carlo simulation (MCS), we propose a combination of a layered white MCS and the adding-doubling method. For slabs with various scattering coefficients assuming a certain anisotropy factor and without absorption, we calculate the transition matrices for light flow with respect to the incident and exit angles. From this series of precalculated transition matrices, we can calculate the transition matrices for the multilayered model with the specific anisotropy factor. The relative errors of the results of this method compared to a conventional MCS were less than 1%. We successfully used this method to estimate the chromophore concentration from the reflectance spectrum of a numerical model of skin and in vivo human skin tissue.