Disparate effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats.
Several studies in patients with primary aldosteronism (PA) have suggested that aldosterone (ALD) is directly contributing to albuminuria. However, there are limited data pertaining to the direct role of ALD in in vivo models in regard to the induction of renal injury and the involved mechanisms. In the present study, we established a high-dose ALD-infused rat model to evaluate urinary albumin excretion rate (UAER) and podocyte damage. Moreover, we studied the effect of eplerenone (EPL), telmisartan (TEL) and amlodipine (AML) on ALD-induced renal structural and functional changes. Immunohistochemical and real-time PCR analyses, and TUNEL assays were performed to evaluate nephrin expression and podocyte injury. ALD-receiving rats (ARR) showed a progressive increase in BP, UAER and proteinuria when compared with control rats (CR). Conversely, BP was significantly reduced in ALD + EPL (A/ERR)-, ALD + AML (A/ARR)- and ALD + TEL (A/TRR)-treated rats. However, UAER and proteinuria were decreased only in A/ERR and A/TRR, but not in A/ARR. Only EPL administration provided protection against ALD-induced podocyte apoptosis. Renal tissue of ARR revealed enhanced expression of nephrin protein and mRNA. This effect of ALD was inhibited by EPL, but not by TEL or AML. Conclusions. ALD induces direct glomerular injury independent of its haemodynamic effects; this effect of ALD is, at least in part, mediated through activation of the mineralocorticoid receptor.


Mechanism of the band gap opening across the order-disorder transition of Si(111)(4 x 1)-In.
The ground state properties of indium atom chains on the Si(111) 8 x 2-In surface and the nature of their insulator-metal (IM) transition near 120 K are under intense dispute. We compare experimental scanning tunneling microscopy (STM) images of the low temperature (LT) 8 x 2 phase with STM image calculations from Density Functional Theory (DFT). Our LT studies clearly indicate the existence of a frozen shear distortion between neighboring atom chains, resulting in the formation of indium hexagons. Tunneling spectra furthermore indicate that the IM transition coincides with the collapse of a approximately 0.3 eV surface-state band gap at the Gamma point of the 4 x 2 Brillouin zone. This implies that the IM transition is driven by a shear phonon, not by Fermi surface nesting.


Boraguanidinates: synthesis, X-ray structures, and reactions of {Li2[(i)Pr2NB(NDipp)2]}2 with p-block and group 12 element halides.
The new Dipp-substituted boranes (Dipp = 2,6-diisopropylphenyl) (i)Pr2NB(NHDipp)2 (5), BrB(NHDipp)2 (7b), and B(NHDipp)3 (8) have been prepared in high yields and characterized in solution by multinuclear NMR spectroscopy ((1)H, (11)B and (13)C) and in the solid state by X-ray crystallography. Reaction of 5 with 2 equiv of (n)BuLi in n-hexane produces {Li2[(i)Pr2NB(NDipp)2]}2 (6) the first example of a stable dilithiated boraguanidinate. The unsolvated complex 6 has a dimeric structure in the solid state. A survey of the reactions of 6 with p-block and Group 12 element halides revealed various types of reactivity including (a) disproportionation (InCl), (b) reduction to the metal (PbCl2, CdCl2, TeBr4, TeI4, and TlCl), and (c) simple metathesis (GeCl2, MgCl2, and ZnCl2). The metathetical products were characterized by multinuclear NMR spectra but, in contrast to the dilithiated complex 6, they readily decompose in non-coordinating solvents to form the diprotonated compound 5.


Act No. 59, Civil Code, 16 July 1987.
Among other things, the Civil Code of Cuba contains the following provisions on intestate succession: "Article 514: 1) The estate falls in the first place to the direct line of descendants, formed by children and other descendants. 2) The children of the deceased inherit in their own right. The inheritance is divided between them in equal parts, without prejudice to the rights of the spouse or of parents who are incapable of working and depended economically on the deceased. 3) Grandchildren and other descendants inherit by right of representation. Article 515: 1) The estate falls in the second place to the parents. 2) If the father and mother survive, they inherit in equal parts, without prejudice to the spouse. Article 516: Parents who are incapable of working and depended economically on the deceased take part [in the estate] with the descendants of the deceased and the surviving spouse and inherit a portion equal to theirs. Article 517: If the surviving spouse takes part in the inheritance with the descendants or parents of the deceased, a portion equal to that of the persons with whom the spouse takes part will fall to the spouse. Article 518: If the deceased has neither descendants nor parents, the entire inheritance will fall to the spouse. Article 520: If there are no heirs falling within the previous sections, the grandparents and other ascendants inherit in equal parts along both the maternal and paternal lines." The Law also contains rules on testate succession. It protects the children of the deceased, their descendants, the spouse, and ascendants of the deceased who are not able to work and were dependent on the deceased. No matter what the provisions of the will left by the deceased, they are to receive half of the estate of the deceased, divided equally among them.


Recent advances in rolling circle amplification-based biosensing strategies-A review.
Rolling circle amplification (RCA) is an efficient enzymatic isothermal reaction that using circular probe as a template to generate long tandem single-stranded DNA or RNA products under the initiation of short DNA or RNA primers. As a simplified derivative of natural rolling circle replication which synthesizes copies of circular nucleic acids molecules such as plasmids, RCA amplifies the circular template rapidly without thermal cycling and finds various applications in molecular biology. Compared with other amplification strategies, RCA has many obvious advantages. Firstly, because of the strict complementarity required in ligation of a padlock probe, it endows the RCA reaction with high specificity and can even be utilized to distinguish single base mismatches. Secondly, through the introduction of multiple primers, exponential amplification can be achieved easily and leads to a good sensitivity. Thirdly, RCA products can be customized by manipulating circular templates to generate functional nucleic acids such as aptamer, DNAzymes and restriction enzyme sites. Moreover, the RCA has good biocompatibility and is especially suitable for in situ detection. Therefore, RCA has attracted considerable attention as an efficient and potential tool for highly sensitive detection of biomarkers. Herein, we comprehensively introduce the fundamental principles of RCA technology, summarize it from three aspects including initiation mode, amplification mode and signal output mode, and discuss the recent application of RCA-based biosensor in this review.


Noninvoluting congenital hemangioma: a rare cutaneous vascular anomaly.
The authors studied a rare, congenital, cutaneous vascular anomaly that grows proportionately with the child and does not regress. A total of 53 patients were compiled from three vascular anomaly centers. These patients' lesions were analyzed for presentation, physical findings, radiologic and histopathologic characteristics, natural history, and outcome after resection. The lesions occurred slightly more often in male patients, always appeared alone, and were located (in order of frequency) in the head/neck region, extremities, and trunk. They were round-to-ovoid in shape, were plaque-like or bossed, occurred in variable shades of pink to purple, and had an average diameter of 5 cm. The overlying skin was frequently punctuated by coarse telangiectasia, often with central or peripheral pallor. The lesions were warm on palpation; fast-flow was further documented by Doppler ultrasonography. Magnetic resonance imaging and angiographic findings were similar to those of common hemangioma of infancy. All lesions were easily excised without recurrence.Histologic examination revealed lobular collections of small, thin-walled vessels with a large, often stellate, central vessel. Interlobular areas contained predominantly dilated, often dysplastic veins; arteries were also increased in number. Small arteries were observed "shunting" directly into lobular vessels or into abnormal extralobular veins. "Hobnailed" endothelial cells lined the small intralobular vessels. Mast cells were increased. Tests for glucose transporter-1, a recently reported reliable marker for common hemangioma of infancy, were negative in all 26 specimens examined. In conclusion, the authors think these clinicopathologic and radiologic features define a rare vascular lesion for which the term "noninvoluting congenital hemangioma" is proposed. These lesions of intrauterine onset may be a variant of common hemangioma of infancy or another hemangiomatous entity with persistent fast-flow.


NOP-Related Mechanisms in Substance Use Disorders.
Nociceptin/orphanin FQ (N/OFQ) is a 17 amino acid peptide that was deorphanized in 1995 and has been widely studied since. The role of the N/OFQ system in drug abuse has attracted researchers' attention since its initial discovery. The first two scientific papers describing the effect of intracranial injection of N/OFQ appeared 20 years ago and reported efficacy of the peptide in attenuating alcohol intake, whereas heroin self-administration was insensitive. Since then more than 100 scientific articles investigating the role of the N/OFQ and N/OFQ receptor (NOP) system in drug abuse have been published. The present article provides an historical overview of the advances in the field with focus on three major elements. First, the most robust data supportive of the efficacy of NOP agonists in treating drug abuse come from studies in the field of alcohol research, followed by psychostimulant and opioid research. In contrast, activation of NOP appears to facilitate nicotine consumption. Second, emerging data challenge the assumption that activation of NOP is the most appropriate strategy to attenuate consumption of substances of abuse. This assumption is based first on the observation that animals carrying an overexpression of NOP system components are more prone to consume substances of abuse, whereas NOP knockout rats are less motivated to self-administer heroin, alcohol, and cocaine. Third, administration of NOP antagonists also reduces alcohol consumption. In addition, NOP blockade reduces nicotine self-administration. Hypothetical mechanisms explaining this apparent paradox are discussed. Finally, we focus on the possibility that co-activation of NOP and mu opioid (MOP) receptors is an alternative strategy, readily testable in the clinic, to reduce the consumption of psychostimulants, opiates, and, possibly, alcohol.


Deregulated sphingolipid metabolism and membrane organization in neurodegenerative disorders.
Sphingolipids are polar membrane lipids present as minor components in eukaryotic cell membranes. Sphingolipids are highly enriched in nervous cells, where they exert important biological functions. They deeply affect the structural and geometrical properties and the lateral order of cellular membranes, modulate the function of several membrane-associated proteins, and give rise to important intra- and extracellular lipid mediators. Sphingolipid metabolism is regulated along the differentiation and development of the nervous system, and the expression of a peculiar spatially and temporarily regulated sphingolipid pattern is essential for the maintenance of the functional integrity of the nervous system: sphingolipids in the nervous system participate to several signaling pathways controlling neuronal survival, migration, and differentiation, responsiveness to trophic factors, synaptic stability and synaptic transmission, and neuron-glia interactions, including the formation and stability of central and peripheral myelin. In several neurodegenerative diseases, sphingolipid metabolism is deeply deregulated, leading to the expression of abnormal sphingolipid patterns and altered membrane organization that participate to several events related to the pathogenesis of these diseases. The most impressive consequence of this deregulation is represented by anomalous sphingolipid-protein interactions that are at least, in part, responsible for the misfolding events that cause the fibrillogenic and amyloidogenic processing of disease-specific protein isoforms, such as amyloid beta peptide in Alzheimer's disease, huntingtin in Huntington's disease, alpha-synuclein in Parkinson's disease, and prions in transmissible encephalopathies. Targeting sphingolipid metabolism represents today an underexploited but realistic opportunity to design novel therapeutic strategies for the intervention in these diseases.


Can temperature-dependent changes in myocardial contractility explain why fish only increase heart rate when exposed to acute warming?
Fish increase heart rate (fH), not stroke volume (VS), when acutely warmed as a way to increase cardiac output (Q). To assess whether aspects of myocardial function may have some basis in determining temperature-dependent cardiac performance, we measured work and power (shortening, lengthening and net) in isolated segments of steelhead trout (Oncorhynchus mykiss) ventricular muscle at the fish's acclimation temperature (14°C), and at 22°C, when subjected to increased rates of contraction (30-105 min-1, emulating increased fH) and strain amplitude (8-14%, mimicking increased VS). At 22°C, shortening power (indicative of Q) increased in proportion to fH, and the work required to re-lengthen (stretch) the myocardium (fill the heart) was largely independent of fH. In contrast, the increase in shortening power was less than proportional when strain was augmented, and lengthening work approximately doubled when strain was increased. Thus, the derived relationships between fH, strain and myocardial shortening power and lengthening work, suggest that increasing fH would be preferable as a mechanism to increase Q at high temperatures, or in fact may be an unavoidable response given constraints on muscle mechanics as temperatures rise. Interestingly, at 14°C, lengthening work increased substantially at higher fH, and the duration of lengthening (i.e. diastole) became severely constrained when fH was increased. These data suggest that myocardial contraction/twitch kinetics greatly constrain maximal fH at cool temperatures, and may underlie observations that fish elevate VS to an equal or greater extent than fH to meet demands for increased Q at lower temperatures.


The Rise of Sonless Families in Asia and North Africa.
A neglected consequence of declining fertility is the likely rise of families with children of one sex-only sons or only daughters. Increases in such families present important demographic shifts that may weaken patrilineal family systems. We assess whether sons-only and daughters-only families rose in Asia and North Africa from the early 1990s to around 2015. Using 88 surveys and two censuses, we examine how the number and sex composition of children of mothers aged 40-49 changed across 20 countries, representing 87% of the region's population and 54% of the global population. We also compare observed trends to sex-indifferent counterfactuals, quantify contributions of fertility declines with decompositions, and investigate subnational trends in China and India. Increases in sons-only families were universal where numbers of children fell. Growth of daughters-only families was suppressed in patrilineal contexts, but these sonless families still rose significantly in 13 of 18 countries where numbers declined. By 2015, over a quarter of families in the region had only sons and nearly a fifth only daughters. There was considerable variation across countries: recent levels ranged from 28.3% to 3.4% daughters-only and from 40.1% to 6.0% sons-only. China and the rest of East Asia had the highest shares.


[Diagnosis of humidifier lung--comparison of various serologic procedures].
Humidifier lung is a form of exogenous-allergic alveolitis caused by microbial growth in humidifiers and air conditioners. It was the aim of the present study to employ and test the ELISA method as an alternative to antibody determination. 134 employees in a large printhouse equipped with air conditioning plant were examined by us. Specific IgG antibodies against contaminated humidifier fluid were determined by means of a solid-phase radioimmunoassay (protein A RAST) that we had developed further. Alternatively we examined a commercially available ELISA method (Pharmacia IgG-RAST 40; enzyme: beta-galactosidase) and an assay based on protein A peroxidase. The influence of different test conditions was studied. All the methods examined proved suitable for determining the specific IgG antibodies. The commercial beta-galactosidase assay could be adapted to application on microtitre plates in a slightly modified form. In the peroxidase assay it is recommended to use very low serum and enzyme concentrations on account of its high sensitivity. Examination of all the 134 serum samples yielded a high correlation between the results of these two non-radioactive methods and those obtained with the protein-A RAST.


Public involvement in health care priority setting: an overview of methods for eliciting values.
There is increasing interest, in the UK and elsewhere, in involving the public in health care priority setting. At the same time, however, there is evidence of lack of clarity about the objectives of some priority setting projects and also about the role of public involvement. Further, some projects display an apparent ignorance of both long-standing theoretical literature and practical experience of methodologies for eliciting values in health care and related fields. After a brief examination of the context of health care priority setting and public involvement, this paper describes a range of different approaches to eliciting values. These approaches are critically examined on a number of dimensions including the type of choice allowed to respondents and the implications of aggregation of values across individuals. Factors which affect the appropriateness of the different techniques to specific applications are discussed. A check-list of questions to be asked when selecting techniques is presented.


Science Translator: An Interview with Louisa Stark.
The Genetics Society of America's Elizabeth W. Jones Award for Excellence in Education recognizes significant and sustained impact on genetics education. The 2015 awardee, Louisa Stark, has made a major impact on global access to genetics education through her work as director of the University of Utah Genetic Science Learning Center. The Center's Learn.Genetics and Teach.Genetics websites are the most widely used online genetic education resources in the world. In 2014, they were visited by 18 million students, educators, scientists, and members of the public. With over 60 million page views annually, Learn.Genetics is among the most used sites on the Web.


Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer: an updated meta-analysis of 13 randomized control trials.
The survival effectiveness of neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) is still unclear based on the study of most up-to-date literatures. This article contributes to this problem by conducting an updated meta-analysis. Based on Burdett et al's (J Thorac Oncol 2006;1:611-621) systematic review, this meta-analysis was conducted. Articles were searched electrically. The possible survival benefit of neoadjuvant chemotherapy was assessed by hazard ratio (HR) in terms of overall survival. A subgroup meta-analysis with only stage III NSCLC was also conducted. The software of Review Manager was used for data management. Thirteen randomized control trials, 6 of which were new ones, were included into this meta-analysis. The overall survival of NSCLC patients in neoadjuvant chemotherapy arm were improved significantly, comparing with those in surgery-alone arm (combined HR = 0.84; 95% confidence interval, 0.77-0.92; p = 0.0001). When only patients with stage III NSCLC were considered, the result was similar (combined HR = 0.84; 95% confidence interval, 0.75-0.95; p = 0.005). Neoadjuvant chemotherapy, as an addition of surgery, would significantly improve the overall survival of operable NSCLC patients, including patients with stage III NSCLC.


Contamination of a multiple-use suction catheter in a closed-circuit system compared to contamination of a disposable, single-use suction catheter.
Multiple-use (M-U) closed-system endotracheal suction catheters are effective in preventing arterial oxygen desaturation in patients on positive end-expiratory pressure (PEEP) and may lessen the frequency of bradycardia and hypotension in unstable patients who are prone to these complications of suctioning. However, because M-U catheters remain attached to the ventilator circuit and are reintroduced repeatedly into the patient's airway over 24 hours or longer, they could become heavily contaminated with pathogens. We hypothesized a risk of autocontamination to the patient by re-inoculation of the respiratory tract with organisms that flourished on the M-U catheter while it was isolated from the patient's immune defenses or antibiotic therapy. We tested this hypothesis in 30 mechanically ventilated adult patients with positive sputum cultures. We measured and compared the amount of bacteria present on an M-U catheter at the end of a 24-hour use period, the amount of bacteria present in the patient's sputum at that time, and the amount of bacteria present on a single-use (S-U) catheter at that time, after it had made one pass into the patient's airway. Organisms recovered and colony counts were also compared to results of a sputum culture obtained before the study began. Fourteen different pathogens or potential pathogens were recovered, in numbers of 2 x 10(1) to 2 x 10(7)colony-forming units. The greatest number of colonies was most often recovered from the sputum specimen, and statistical analysis showed no differences in rate or magnitude of contamination between M-U and S-U catheters.(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment of sex offenders with medroxyprogesterone acetate.
Forty-eight male patients with long-standing histories of deviant sexual behavior received medroxyprogesterone acetate and milieu therapy for up to 12 months. Forty subjects responded positively, all within 3 weeks, with diminished frequency of sexual fantasies and arousal, decreased desire for deviant sexual behavior, increased control over sexual urges, and improvement in psychosocial functioning. Improvement in deviant sexual behavior and psychosocial functioning was maintained after treatment ended, and there was no evidence of permanent physiological changes. The author suggests that medroxyprogesterone acetate associated with counseling may be the treatment of choice for patients with long-term deviant sexual behavior. He discusses the ethical issues involved.


Acyl Transfer Catalytic Activity in De Novo Designed Protein with N-Terminus of α-Helix As Oxyanion-Binding Site.
The design of catalytic proteins with functional sites capable of specific chemistry is gaining momentum and a number of artificial enzymes have recently been reported, including hydrolases, oxidoreductases, retro-aldolases, and others. Our goal is to develop a peptide ligase for robust catalysis of amide bond formation that possesses no stringent restrictions to the amino acid composition at the ligation junction. We report here the successful completion of the first step in this long-term project by building a completely de novo protein with predefined acyl transfer catalytic activity. We applied a minimalist approach to rationally design an oxyanion hole within a small cavity that contains an adjacent thiol nucleophile. The N-terminus of the α-helix with unpaired hydrogen-bond donors was exploited as a structural motif to stabilize negatively charged tetrahedral intermediates in nucleophilic addition-elimination reactions at the acyl group. Cysteine acting as a principal catalytic residue was introduced at the second residue position of the α-helix N-terminus in a designed three-α-helix protein based on structural informatics prediction. We showed that this minimal set of functional elements is sufficient for the emergence of catalytic activity in a de novo protein. Using peptide-αthioesters as acyl-donors, we demonstrated their catalyzed amidation concomitant with hydrolysis and proved that the environment at the catalytic site critically influences the reaction outcome. These results represent a promising starting point for the development of efficient catalysts for protein labeling, conjugation, and peptide ligation.


Electron-Precise Semiconducting ReGa2Ge: Extending the IrIn3 Structure Type to Group 7 of the Periodic Table.
Intermetallic compounds with semiconducting properties are rare, but they give rise to advanced materials for energy conversion and saving applications. Here, we present ReGa2Ge, a new electron-precise narrow-gap intermetallic semiconductor. The compound crystallizes in the IrIn3 structure type (space group P42/mnm, a = 6.5734(3) Å, c = 6.7450(8) Å, and Z = 4), where Re atoms occupy the Ir site, while Ga and Ge jointly populate the In sites. 69,71Ga nuclear quadrupole resonance spectroscopy indicates nonstatistical partially ordered distribution of Ga and Ge over two available crystallographic sites; however, the Ga:Ge ratio is exactly 2:1 without noticeable homogeneity range. The stoichiometry of ReGa2Ge ensures its precise valence electron count, which is 17 e- per formula unit. Accordingly, a narrow energy gap opens up at the Fermi energy in the electronic structure. Electrical resistivity, Seebeck coefficient, and thermal conductivity are in agreement with the semiconducting behavior deduced from the electronic structure calculations and point to prospective thermoelectric properties at high temperatures. Bonding analysis reveals dominant covalency in Re-E (E = Ga, Ge) and Re-Re interactions.


Yield improvement of exopolysaccharides by screening of the Lactobacillus acidophilus ATCC and optimization of the fermentation and extraction conditions.
Exopolysacharides (EPS) produced by Lactobacillus acidophilus play an important role in food processing with its well-recognized antioxidant activity. In this study, a L. acidophilus mutant strain with high-yielding EPS (2.92±0.05 g/L) was screened by chemical mutation (0.2 % diethyl sulfate). Plackett-Burman (PB) design and response surface methodology (RSM) were applied to optimize the EPS fermentation parameters and central composite design (CCD) was used to optimize the EPS extraction parameters. A strain with high-yielding EPS was screened. It was revealed that three parameters (Tween 80, dipotassium hydrogen phosphate and trisodium citrate) had significant influence (P < 0.05) on the EPS yield. The optimal culture conditions for EPS production were: Tween 80 0.6 mL, dipotassium hydrogen phosphate 3.6 g and trisodium citrate 4.1 g (with culture volume of 1 L). In these conditions, the maximum EPS yield was 3.96±0.08 g/L. The optimal extraction conditions analyzed by CCD were: alcohol concentration 70 %, the ratio of material to liquid (M/L ratio) 1:3.6 and the extraction time 31 h. In these conditions, the maximum EPS extraction yield was 1.48±0.23 g/L. It was confirmed by the verification experiments that the EPS yield from L. acidophilus mutant strains reached 5.12±0.73 g/L under the optimized fermentation and extraction conditions, which was 3.8 times higher than that of the control (1.05±0.06 g/L). The results indicated that the strain screening with high-yielding EPS was successful and the optimized fermentation and extraction conditions significantly enhanced EPS yield. It was efficient and industrially promising.


FDA Public Workshop Summary: Advancing Animal Models for Antibacterial Drug Development.
The U.S. Food and Drug Administration (FDA) hosted a public workshop entitled "Advancing Animal Models for Antibacterial Drug Development" on 5 March 2020. The workshop mainly focused on models of pneumonia caused by Pseudomonas aeruginosa and Acinetobacter baumannii The program included discussions from academic investigators, industry, and U.S. government scientists. The potential use of mouse, rabbit, and pig models for antibacterial drug development was presented and discussed.


Crosswalk algorithms for the conversion of mean EQ-5D indices calculated with different value sets.
The EQ-5D questionnaire of EuroQol is an important tool, not only for researchers, but also for quality registers. Until 2013, Sweden did not have a country-specific value set to convert the EQ-5D health states into a single index. Commonly, the UK time trade-off (UK TTO) value set has been used. The study reported here aimed to establish an easy to use tool for the bidirectional crosswalk of the mean EQ-5D values based on two different value sets: the UK TTO and the Swedish TTO value sets. Using an artificial data set encompassing all possible EQ-5D outcomes, we calculated the EQ-5D index using both the UK TTO and Swedish TTO value sets. Thereafter we modelled the relationship between the two indices using least-squares regression and major axis regression. A series of simulations was run to assess the feasibility of the obtained crosswalk algorithms. Major axis regression was superior to ordinary least-squares regression. Converting the mean EQ-5D values from the UK TTO scale to the Swedish TTO scale was more accurate than the inverse conversion. Values close to the floor and ceiling of the EQ-5D index were more challenging to crosswalk. CONCLUSIONS WE ESTABLISHED ALGORITHMS BASED ON MAJOR AXIS REGRESSION TO CROSSWALK EQ-5D VALUES BASED ON THE UK TTO AND THE SWEDISH TTO VALUE SETS THE PRESENTED ALGORITHM MAY FACILITATE COMPARISONS OF EQ-5D VALUES WHEN ONLY MEAN VALUES ARE AVAILABLE THE EXISTENCE OF A CROSSWALK ALGORITHM WILL EASE THE TRANSITION FROM THE UK TTO TO THE SWEDISH TTO VALUE SET.


Early evidence of efficacy for orally administered SPM-enriched marine lipid fraction on quality of life and pain in a sample of adults with chronic pain.
Marine lipids contain omega-3 fatty acids that can be metabolized into anti-inflammatory and pro-resolving mediators-namely 17-HDHA and 18-HEPE-which can serve as modulators of the pain experience. The purpose of this study was to determine the impact of 4 weeks of oral supplementation with a fractionated marine lipid concentration, standardized to 17-HDHA and 18-HEPE, on health-related quality of life and inflammation in adults with chronic pain. This study was a prospective, non-randomized, open-label clinical trial. Forty-four adults with ≥ moderate pain intensity for at least 3 months were recruited. The primary outcome was change in health-related quality of life (QOL) using the Patient Reported Outcomes Measurement Information System-43 Profile (PROMIS-43) and the American Chronic Pain Association (ACPA) QOL scale. Exploratory outcomes assessed safety and tolerability, changes in anxiety and depression, levels of pain intensity and interference, patient satisfaction, and impression of change. Changes in blood biomarkers of inflammation (hs-CRP and ESR) were also explored. Outcome measures were collected at Baseline, Week 2, and Week 4 (primary endpoint). At Week 4, PROMIS-43 QOL subdomains changed with significance from baseline (p < 0.05), with borderline changes in the ACPA Quality of Life scale (p < 0.052). Exploratory analyses revealed significant changes (p < 0.05) in all measures of pain intensity, pain interference, depression, and anxiety. There were no statistically significant changes in either hs-CRP or ESR, which stayed within normal limits. We conclude that oral supplementation with a fractionated marine lipid concentration standardized to 17-HDHA and 18-HEPE may improve quality of life, reduce pain intensity and interference, and improve mood within 4 weeks in adults with chronic pain. The consistency and magnitude of these results support the need for placebo-controlled clinical trials of marine lipid concentrations standardized to 17-HDHA and 18-HEPE. Trial registration ClinicalTrials.gov: Influence of an Omega-3 SPM Supplement on Quality of Life, NCT02683850. Registered 17 February 2016-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02683850 .


Identification of an Nav1.1 sodium channel (SCN1A) loss-of-function mutation associated with familial simple febrile seizures.
Febrile seizures (FS) affect 5-12% of infants and children up to 6 years of age. There is now epidemiological evidence that FS are associated with subsequent afebrile and unprovoked seizures in approximately 7% of patients, which is 10 times more than in the general population. Extensive genetic studies have demonstrated that various loci are responsible for familial FS, and the FEB3 autosomal-dominant locus has been identified on chromosome 2q23-24, where the SCN1A gene is mapped. However, gene mutations causing simple FS have not been found yet. Here we show that the M145T mutation of a well conserved amino acid in the first transmembrane segment of domain I of the human Na(v)1.1 channel alpha-subunit cosegregates in all 12 individuals of a large Italian family affected by simple FS. Functional studies in mammalian cells demonstrate that the mutation causes a 60% reduction of current density and a 10-mV positive shift of the activation curve. Thus, M145T is a loss-of-function mutant. These results show that monogenic FS should also be considered a channelopathy.


Inhibition of macrophage activation by the myxoma virus M141 protein (vCD200).
The M141 protein of myxoma virus (MYXV) is a viral CD200 homolog (also called vOX-2) that inhibits macrophage activation in infected rabbits. Here, we show that murine myeloid RAW 264.7 cells became activated when infected with MYXV in which the M141 gene was deleted (vMyx-M141KO) but not with the parental wild-type MYXV. Moreover, transcript and protein levels of tumor necrosis factor and granulocyte colony-stimulating factor were rapidly upregulated in an NF-kappaB-dependent fashion in the RAW 264.7 cells infected with vMyx-M141KO. M141 protein is present in the virion and counteracts this NF-kappaB activation pathway upon infection with the wild-type MYXV. Our data suggest that upregulation of these classic macrophage-related proinflammatory cytokine markers following infection of myeloid cells with the M141-knockout MYXV is mediated via the rapid activation of the cellular NF-kappaB pathway.


Benefits and burdens: researching the consequences of migration in the Sahel.
The consequences of rural out-migration for women and natural resource management are analyzed for four locations in the Sahel region of Africa, located in Burkina Faso, Senegal, Sudan, and Mali. The results show that "the impact of migration on women's management of natural resources varies considerably depending on prevailing gender divisions and relations of labour, of land access and control, and of responsibilities towards family and personal production."


Association between serum calcium and phosphorus concentrations with non-alcoholic fatty liver disease in Korean population.
Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is interrelated with renal dysfunction and disturbed bone metabolism, both of which play a key role in calcium and phosphorus homeostasis. We investigated the association between NAFLD and serum calcium and phosphorus levels in Korean subjects. We performed a cross-sectional analysis of 16,592 subjects undergoing a general health checkup. NAFLD was assessed based on ultrasonographically detected fatty liver in the absence of excessive alcohol consumption and other causes of liver disease. The proportion of the population with fatty liver detected by ultrasonography was 43.2% for males and 17.6% for females. We observed that a higher serum albumin-corrected calcium (Ca(c)) level was associated with smoking, hypertension, and unfavorable metabolic parameters in both genders, but the serum phosphorus levels showed an inconsistent correlation with metabolic abnormalities. After adjusting for age, gender, waist circumference, body mass index, smoking status, exercise, diabetes, hypertension, lipid profiles, and renal function, serum Cac , phosphorus, and Cac -phosphorus products were independent risk factors for fatty liver (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.49-1.95, P < 0.001; OR: 1.34, 95% CI: 1.22-1.48, P < 0.001; and OR: 1.20, 95% CI: 1.14-1.26, P < 0.001, respectively), and the risk of fatty liver increased in a graded manner over the quartiles. Serum calcium and phosphorus levels are significantly associated with NAFLD. Further investigation is needed to verify whether calcium and phosphorus levels indicate a higher risk of NAFLD.


Incidence and associated factors of HIV drug resistance in Chinese HIV-infected patients receiving antiretroviral treatment.
A critical indicator of the future success of highly active antiretroviral therapy (HAART) is the incidence of HIV drug resistance, which has not been studied in China on the national scale. HIV drug resistance baseline survey was conducted in the eight provinces with the largest numbers of patients on HAART in 2009, and a prospective cohort study with 12-month follow-up was completed in 2010. Patients completed an interviewer-administrated questionnaire and provided blood for CD4+ T-lymphocyte count (CD4 count), HIV viral load (VL), and HIV drug resistance genotyping. Factors associated with incidence of HIVDR were identified by Cox regression analysis. The overall prevalence of HIV RNA ≥ 1000 copies/ml and HIVDR at baseline was 12.4% and 5.6%, respectively. Incidence of HIVDR in the one year follow-up was 3.5 per 100 person years. Independently associated factors were started treatment with a didanosine-based regimen, received care at township hospital or village clinic, low baseline CD4 counts, and high baseline VL. The incidence of HIVDR in China was higher than that of some developed countries. China urgently needs to provide comprehensive education and training to doctors at village clinics and township hospitals to improve quality community-based care and treatment.


4,4,6a,6b,11,12,14b-Heptamethyl-16-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,9,10,11,12,12a,14a,14b-octa-deca-hydro-12b,8a-(epoxy-methano)-picen-3-yl acetate.
The title compound, C32H48O4, which was extracted from the bark of Rhododendron arboreum, consists of five fused rings to which an acetate and seven methyl groups are attached. The A, D and E rings adopt chair conformations, the B ring is in a distorted chair and the C ring is in a half-chair conformation. The five-membered ring formed by the lactone group, which bridges from the A/B to the B/C ring junctions, is an approximate envelope with the C atom of the methyne group as the flap [displacement from the other four atoms = 0.753 (2) Å]. There are no identified directional inter-actions in the crystal structure.


Current opinions concerning the restoration of endodontically treated teeth: basic principles.
The goal of this general article is to present a survey of the current knowledge about the clinical approach of restoring endodontically treated teeth. The best way to restore teeth after root canal treatment has long been and still is a controversial subject of debate to this day. The clinical approach of restoring endodontically treated teeth needs taking into consideration several issues: aims of coronal restoration, criteria for establishing the various modalities of coronal restoration, clinical solutions of restoring teeth after endodontic treatment, guidelines regarding restorative materials and techniques, possibilities and limits of restoration using direct adhesive materials and techniques. The aims of coronal restoration of endodontically treated teeth are generally considered to be the following ones: to prevent recontamination of the root canal system and/or periapical space, to replace missing hard dental tissues and to restore coronal morphology and functions, to provide the necessary strength for the restoration/tooth complex in order to withstand functional stress and prevent crown and/or root fracture. The criteria for establishing the modalities of coronal restoration for endodontically treated teeth are: amount and quality of remaining hard dental tissues, topography and coronal morphology of the tooth, functional occlusal forces that the restoration/tooth complex has to withstand, restoring requirements in order to include the treated tooth in a comprehensive oral rehabilitation treatment plan, esthetic requirements.


Phenotypic plasticity in response to climate change: the importance of cue variation.
Phenotypic plasticity is a major mechanism of response to global change. However, current plastic responses will only remain adaptive under future conditions if informative environmental cues are still available. We briefly summarize current knowledge of the evolutionary origin and mechanistic underpinnings of environmental cues for phenotypic plasticity, before highlighting the potentially complex effects of global change on cue availability and reliability. We then illustrate some of these aspects with a case study, comparing plasticity of blue tit breeding phenology in two contrasted habitats: evergreen and deciduous forests. Using long-term datasets, we investigate the climatic factors linked to the breeding phenology of the birds and their main food source. Blue tits occupying different habitats differ extensively in the cues affecting laying date plasticity, as well as in the reliability of these cues as predictors of the putative driver of selective pressure, the date of caterpillar peak. The temporal trend for earlier laying date, detected only in the evergreen populations, is explained by increased temperature during their cue windows. Our results highlight the importance of integrating ecological mechanisms shaping variation in plasticity if we are to understand how global change will affect plasticity and its consequences for population biology. This article is part of the theme issue 'The role of plasticity in phenotypic adaptation to rapid environmental change'.


Malignant tumors of the nasal cavity: review of a 60-case series.
Sixty cases of primary malignant tumor of the nasal cavity treated in our hospital between 1962 and 1993 were reviewed. Males were affected 2.8 times more frequently than females. The age at the first consultation ranged from 11 to 92 years, with a mean of 55.1 years. The peak distribution was seen in the 6th decade. Twenty-six cases were epithelial malignancies (squamous cell carcinoma 15; adenocarcinoma 3; adenoid cystic carcinoma 3; undifferentiated carcinoma 3; mucoepidermoid carcinoma 1; malignant mixed tumor 1), while 34 cases were non-epithelial malignancies (malignant melanoma 14; malignant lymphoma 14; plasmacytoma 3; olfactory neuroblastoma 2; rhabdomyosarcoma 1). The most common symptom on presentation was nasal obstruction (66.7%), followed by epistaxis (55.0%). The first recurrence was local in 19 patients, whereas cervical lymph node metastasis occurred in three patients, bone metastasis in two, intraperitoneal metastasis in two, and brain metastasis in one. The overall five-year cumulative survival rate was 48.0%. The five-year survival rates for squamous cell carcinoma, malignant melanoma, and malignant lymphoma were 57.0%, 31.0%, and 40.0%, respectively.


Variant pathogenic prediction by locus variability: the importance of the current picture of evolution.
Accurate detection of pathogenic single nucleotide variants (SNVs) is a key challenge in whole exome and whole genome sequencing studies. To date, several in silico tools have been developed to predict deleterious variants from this type of data. However, these tools have limited power to detect new pathogenic variants, especially in non-coding regions. In this study, we evaluate the use of a new metric, the Shannon Entropy of Locus Variability (SELV), calculated as the Shannon entropy of the variant frequencies reported in genome-wide population studies at a given locus, as a new predictor of potentially pathogenic variants in non-coding nuclear and mitochondrial DNA and also in coding regions with a selective pressure other than that imposed by the genetic code, e.g splice-sites. For benchmarking, SELV was compared to predictors of pathogenicity in different genomic contexts. In nuclear non-coding DNA, SELV outperformed CDTS (AUCSELV = 0.97 in ROC curve and PR-AUCSELV = 0.96 in Precision-recall curve). For non-coding mitochondrial variants (AUCSELV = 0.98 in ROC curve and PR-AUCSELV = 1.00 in Precision-recall curve) SELV outperformed HmtVar. Moreover, SELV was compared against two state-of-the-art ensemble predictors of pathogenicity in splice-sites, ada-score, and rf-score, matching their overall performance both in ROC (AUCSELV = 0.95) and Precision-recall curves (PR-AUC = 0.97), with the advantage that SELV can be easily calculated for every position in the genome, as opposite to ada-score and rf-score. Therefore, we suggest that the information about the observed genetic variability in a locus reported from large scale population studies could improve the prioritization of SNVs in splice-sites and in non-coding regions.


A Large-Scale Dataset and Deep Learning Model for Detecting and Counting Olive Trees in Satellite Imagery.
Since the Pre-Roman era, olive trees have a significant economic and cultural value. In 2019, the Al-Jouf region, in the north of the Kingdom of Saudi Arabia, gained a global presence by entering the Guinness World Records, with the largest number of olive trees in the world. Olive tree detecting and counting from a given satellite image are a significant and difficult computer vision problem. Because olive farms are spread out over a large area, manually counting the trees is impossible. Moreover, accurate automatic detection and counting of olive trees in satellite images have many challenges such as scale variations, weather changes, perspective distortions, and orientation changes. Another problem is the lack of a standard database of olive trees available for deep learning applications. To address these problems, we first build a large-scale olive dataset dedicated to deep learning research and applications. The dataset consists of 230 RGB images collected over the territory of Al-Jouf, KSA. We then propose an efficient deep learning model (SwinTUnet) for detecting and counting olive trees from satellite imagery. The proposed SwinTUnet is a Unet-like network which consists of an encoder, a decoder, and skip connections. Swin Transformer block is the fundamental unit of SwinTUnet to learn local and global semantic information. The results of an experimental study on the proposed dataset show that the SwinTUnet model outperforms the related studies in terms of overall detection with a 0.94% estimation error.


Bioelectrical potentials of Philodendron cordatum: a new method for investigation of behavior in plants.
We explored the prospect of using the bioelectrical potentiaLs of Philodendron cordatum as a new method for studying the behavior of plants. The bioelectrical potentials were recorded from equipment typically associated with EEG recordings. Plants were exposed to a 6-hr. training period of light only, dark only, or alternating 1-min. periods of light/dark. Following training, all plants were exposed to a 10-min. testing period in darkness during which bioelectrical potentials were recorded. Power of the bioelectric potentials was compared between groups of plants for frequencies between 0.1 and 10.0 Hz. Significant main effects of group and frequency were found, raising questions about the possibility of "learning" in P. cordatum.


The impact of COVID-19 on the eating habits of families engaged in a healthy eating pilot trial: a thematic analysis.
The eating habits of children and adults have been impacted by the COVID-19 pandemic, with evidence of increases in snacking and emotional eating, including eating to relieve boredom. We explored the experiences of families with children aged 4-8 years who had recently participated in a healthy eating pilot trial when the first national lockdown began in England. Eleven mothers were interviewed in April and May 2020. Interview questions were developed based on the COM-B model of behaviour. Four main themes were constructed using inductive thematic analysis. The first theme related to an initial panic phase, in which having enough food was the primary concern. The second related to ongoing challenges during the lockdown, with sub-themes including difficulties accessing food, managing children's food requests and balancing home and work responsibilities. The perception that energy-dense foods met families' needs during this time led to increased purchasing of (and thus exposure to) energy-dense foods. In the third theme, families described a turning point, with a desire to eat a healthier diet than they had in the early stages of the lockdown. Finally, in the fourth theme, families reported a number of strategies for adapting and encouraging a balanced diet with their children. Our results suggest that even if parents have the capability (e.g. knowledge) and motivation to provide a healthy diet for their family, opportunity challenges (e.g. time, access to resources, environmental stressors) mean this is not always practical. Healthy eating interventions should not assume parents lack motivation and should be sensitive to the context within which parents make feeding decisions.


Use of ECT in California, revisited: 1984-1994.
The use of ECT in California was examined from 1984 to 1994 and compared with a previous study examining use from 1977 to 1983. Data were collected from legally required reports submitted to the state for all ECT performed. A total of 28,437 patients (mean = 2585.18 per year) received a total of 160,847 treatments with a mean rate of 0.90 patients/10,000 population. The rate in 1984 (1.15) was similar to the mean rate for 1977-1983 (1.12). The rate dropped in 1986 (0.92) and again in 1991 (0.74). There were 821 patients (2.89% of total) judged to be incapable of giving informed consent who received ECT after a court review. This is similar to the rate of 3% for 1977 to 1983. The number of counties where ECT was available increased from 15 in 1983 to 19 in 1991 and returned to 15 in 1994. The number of facilities providing ECT increased from 62 in 1983 to 83 in 1990 and decreased to 69 in 1994. White patients comprised 91.5% of ECT recipients. Three deaths were reported for a rate of 0.19 deaths/10,000 treatments. Despite its safety and efficacy, the availability of ECT in California continues to remain limited geographically and socioeconomically. The rate of its use has declined. Access to ECT is most limited for public patients. While some of the decline may be related to the introduction of new antidepressants and the rapid expansion of managed care, complex legal regulation bears much of the responsibility.


Computed tomography image analyzer: segmentation applying active contour models--"snakes".
Many diagnostic and therapeutic procedures depend on medical images. In order to overcome imperfections of obtained images which are due to acquisition process and to obtain new information from available images, many techniques have been developed. In this study relatively new method of image segmentation, active contour model--"snakes" was applied in analyzing computed tomography (CT) images in patients with acute head trauma. Using this method, lesion to brain (LBR) and ventricle to brain ratio (VBR) were obtained accurately. Quantitative variable LBR, is significantly higher in patients with other pathologic CT findings and who do not survive during hospitalization. Thus, by applying segmentation "snakes" model it is possible to extract maximum information from available CT scans. These variables could be basis for medical decision making in patients with acute head trauma.


Advance Directives in Oncology and Haematology: A Long Way to Go-A Narrative Review.
Patients living with cancer often experience serious adverse events due to their condition or its treatments. Those events may lead to a critical care unit admission or even result in death. One of the most important but challenging parts of care is to build a care plan according to the patient's wishes, meeting their goals and values. Advance directives (ADs) allow everyone to give their preferences in advance regarding life sustaining treatments, continuation, and withdrawal or withholding of treatments in case one is not able to speak their mind anymore. While the absence of ADs is associated with a greater probability of receiving unwanted intensive care around the end of their life, their existence correlates with the respect of the patient's desires and their greater satisfaction. Although progress has been made to promote ADs' completion, they are still scarcely used among cancer patients in many countries. Several limitations to their acceptance and use can be detected. Efforts should be made to provide tailored solutions for the identified hindrances. This narrative review aims to depict the situation of ADs in the oncology context, and to highlight the future areas of improvement.


Carcinoma of the esophagus presenting with esophagocutaneous fistula--a case report.
An interesting manifestation of carcinoma of the esophagus, hitherto undescribed is reported. The patient at the time of diagnosis had presented with an esophagocutaneous fistula. He was treated by feeding jejunostomy and local palliative radiotherapy and showed good clinical improvement. The extreme rarity of such a presentation is highlighted.


Pharmacokinetics and pharmacodynamics of different doses of Irtemazole in repeated application.
Irtemazole, a new uricosuric substance, was tested in 12 normouricemic subjects in doses between 6.25-37.5 mg applied twice daily for 7 days per os. The plasma uric acid level decreased in all subjects, to a constant level within 1-2 days with application of the higher doses, and within 2-3 days with application of the lower doses, and was maintained as long as irtemazole was given. The average decrease of plasma uric acid was 20.4% at a dose of 6.25 mg irtemazole, 22.7% at 12.5 mg, 42.0% at 25 mg, and 45.7% at 37.5 mg. The renal uric acid excretion and the uric acid clearance increased to a constant level within 1 day of irtemazole application. The initial levels of plasma uric acid, uric acid excretion, and uric acid clearance were reached after 1-2 days after cessation of irtemazole. Within 1 to 2 days after ingestion of irtemazole a constant plasma irtemazole level and renal irtemazole excretion were observed in all doses throughout the application period. One to 2 days after discontinuation of irtemazole it was no longer detectable in plasma and urine. No side effects were found.


Characteristics of emergency department admissions with congestive heart failure in the United States: a Nationwide cross-sectional study.
To understand the characteristics and clinical presentation of patients with Congestive Heart Failure (CHF) visiting the emergency department (ED), and to examine the factors associated with clinical outcomes and medical resource utilization amongst the studied population. We analyzed the 2014-2016 ED visit data collected by the National Hospital Ambulatory Medical Care Survey Emergency Department Subfile. We described patients' characteristics and clinical outcomes after ED visits with CHF vs. without CHF. Logistic regression models were used to estimate the association between these characteristics and CHF. ED visits with CHF visits represented 3.9% of annual ED visits (3,647,113 out of 92,899,685). ED patients with CHF were mostly non-Hispanic White (69.9%). Compared with other ED patients, those with CHF were older, including 71.2% that were were older than 60. ED patients with CHF were more likely to be admitted to the hospital (aOR: 2.56; 95% CI: 2.28-2.87) and intensive care unit (ICU) (aOR: 2.19; 95% CI: 1.77-2.71). This study describes the demographic, socioeconic, and clinical characteristics of patients who present to the ED with CHF through analysis of a comprehensive national survey. These patients require a higher level of emergency care due to their higher chance of admittance to the hospital and ICU.


High frequency of HLA-Bw16 in patients with anorexia nervosa.
Anorectic patients (N = 37) had a higher frequency of HLA-Bw16 than normal controls, due to the higher frequency of HLA-Bw38. They also had a higher rate of A26-Bw38. HLA typing may lead to hypotheses about the biology of anorexia nervosa.


Xanthelasma palpebrarum.
The management of xanthelasma can be challenging, as evidenced by our own experiences as well as that of other physicians. Appreciating the difficulties is important, so as to inform the patient of the risks of recurrences after surgical excision and to plan the surgical procedure to prevent ocular complications such as ectropion. The patient with xanthelasma who desires a blepharoplasty is an especially interesting topic. A conservative approach, at times using staged excisions, as discussed in this article, will help achieve the desired result and assure patient satisfaction.


Compression of random coils due to macromolecular crowding.
The conformation of a linear polymer chain is studied as a function of the concentration of a macromolecular crowding agent by neutron scattering. Excluded volume to random coil due to macromolecular crowding in cells is predicted to exert a compressive force that will tend to reduce its size. It is shown that when reducing free volume due to macromolecular crowding, we observe a compression of the polymer chain with a reduction in its radius of gyration of up to approximately 30% and that the effective chain-chain interactions are strongly modified.


Human papillomavirus vaccination rates in adolescents with cerebral palsy compared to the general population.
To determine whether adolescents with cerebral palsy (CP) initiate and are up-to-date with the human papillomavirus (HPV) immunization series compared to adolescents in the general population. Data on initiation and up-to-date status of the HPV series were collected on adolescents with CP aged 13-17 years old (n = 74) via retrospective medical record review and compared to 616 age-matched peers from the National Immunization Survey, Teen 2019. Analysis by gender, Gross Motor Functional Classification System (GMFCS) level, and ambulatory status was performed in the CP group. Adolescents with CP were three times less likely to start (p < 0.001) and two times less likely to be up-to-date (p = 0.004) with the HPV immunization series compared to age-matched peers. When the HPV immunization series was initiated in adolescents with CP, these adolescents were as likely to complete the series (p = 0.400), with 83.3% being up-to-date. In those with CP, there was no statistical difference in status of the HPV immunization series when comparing gender, GMFCS level, or ambulatory status. Adolescents with CP were less likely to start the HPV immunization series; however, they were as likely to be up-to-date with the series if it was initiated. This presents an opportunity for pediatric physiatrists to help reduce the disparity.


Optical sensors based on whispering gallery modes in fluorescent microbeads: response to specific interactions.
Whispering gallery modes (WGMs) in surface-fixated fluorescent polystyrene microbeads are studied in view of their capability of sensing the formation of biochemical adsorption layers on their outer surface with the well-established biotin-streptavidin specific binding as the model system. Three different methods for analysis of the observed shifts in the WGM wavelength positions are applied and used to quantify the adsorbed mass densities, which are then compared with the results of a comparative surface plasmon resonance (SPR) study.


WebGeSTer DB--a transcription terminator database.
We present WebGeSTer DB, the largest database of intrinsic transcription terminators (http://pallab.serc.iisc.ernet.in/gester). The database comprises of a million terminators identified in 1060 bacterial genome sequences and 798 plasmids. Users can obtain both graphic and tabular results on putative terminators based on default or user-defined parameters. The results are arranged in different tiers to facilitate retrieval, as per the specific requirements. An interactive map has been incorporated to visualize the distribution of terminators across the whole genome. Analysis of the results, both at the whole-genome level and with respect to terminators downstream of specific genes, offers insight into the prevalence of canonical and non-canonical terminators across different phyla. The data in the database reinforce the paradigm that intrinsic termination is a conserved and efficient regulatory mechanism in bacteria. Our database is freely accessible.


[Secondary osteoporosis. Bone disease in liver cirrhosis.]
Because of improved treatment of cirrhosis, patients are living longer and bone disesae such as osteoporosis is found in an increasing proportion of patients with cirrhosis. As the causes for bone diseases in cirrhosis, inhibition of vitamin D hydration and inhibition of vitamin D absorption due to decreased secretion of cholic acid have been reported, and various other causes are concerned. These bone diseases have been treated with bisphosphonates, but no definite opinion has been obtained in relation to therapeutic effects. In recent years, non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)is increasing in prevalence. Relation of these deseases with osteoporosis, however, is not well known and further investigation is needed.


The effects of cyclooxygenase-2 gene silencing by siRNA on cell proliferation, cell apoptosis, cell cycle and tumorigenicity of Capan-2 human pancreatic cancer cells.
The prognosis of pancreatic cancer is still very poor. No specific effective gene therapy for pancreatic cancer has been found. As a key enzyme of the metabolic process of arachidonic acid, cyclooxygenase-2 (COX-2) has been found to be closely related to the tumorigenesis of epithelial cancers. However, the antitumor effect of small interfering RNA (siRNA) targeting COX-2 in pancreatic cancer has not yet been verified. Therefore, the aim of this study was to investigate the effects of COX-2 gene silencing by siRNA on cell proliferation, cell apoptosis, cell cycle and tumorigenicity of pancreatic cancer cells. COX-2 mRNA was detected by RT-PCR and real-time PCR. COX-2 protein was detected by Western blotting. The cell proliferation was measured by cell counting using microscopy. The cell apoptosis and cell cycle were measured by flow cytometry. The tumorigenicity of Capan-2 pancreatic cancer cells transfected with COX-2 siRNA was evaluated using a nude mouse xenograft model. The expression of COX-2 mRNA as well as COX-2 protein were downregulated after COX-2 siRNA transfection. COX-2 siRNA could inhibit the growth of Capan-2 cells significantly by decreasing the cell proliferation, increasing cell apoptosis and regulating cell cycle as well. In vivo experiments demonstrated that the mean volume and weight of subcutaneous xenografts in nude mice derived from Capan-2 cells transfected with COX-2 siRNA were significantly decreased. COX-2 siRNA could inhibit the growth of Capan-2 pancreatic cancer cells and also decrease the tumorigenicity of Capan-2 cells, implicating a new potential therapeutic target in pancreatic cancer.


Na-Stimulation of Photosynthesis in the Cyanobacterium Synechococcus UTEX 625 Grown on High Levels of Inorganic Carbon.
Photosynthesis of washed cells of Synechococcus UTEX 625 grown on 5% CO(2) was markedly stimulated (647 +/- 50%) at pH 8.0 by the addition of low concentrations of NaCl (concentration required for half-maximal response, K((1/2),) = 18 micromolar). Studies with KCl and Na(2)SO(4) showed that the stimulation was due to Na(+). Photosynthesis at pH 6.1 was only slightly stimulated by Na(+). The response of photosynthesis at pH 8.0 to [Na(+)] was strongly sigmoidal for dissolved inorganic carbon ([DIC] </= 500 micromolar). Cells grown with high total [DIC], but air-levels of CO(2), at pH 9.6 showed the same response to low [Na(+)]. The absence of Na(+) could be partially, but not completely overcome, by higher [DIC]. Various methods for examining CO(2) or HCO(3) (-) use (K((1/2)) (CO(2) ) determination; isotopic disequilibrium; and consideration of HCO(3) (-) dehydration rate) were consistent with CO(2) use by the cells, but HCO(3) (-) use could not be ruled out. Isotopic disequilibrium studies showed that CO(2) use was stimulated by Na(+). Cells grown on 5% CO(2) accumulated DIC against a concentration gradient by a process (or processes) dependent on Na(+). No evidence for uptake of Na(+) concomitant with DIC uptake could be found. The lack of O(2) evolution during the initial and most rapid period of DIC accumulation suggested that the required energy was obtained from cyclic photophosphorylation.


OH-initiated heterogeneous oxidation of cholestane: a model system for understanding the photochemical aging of cyclic alkane aerosols.
Aerosols containing aliphatic hydrocarbons play a substantial role in the urban atmosphere. Cyclic alkanes constitute a large fraction of aliphatic hydrocarbon emissions originating from incomplete combustion of diesel fuel and motor oil. In the present study, cholestane (C27H48) is used as a model system to examine the OH-initiated heterogeneous oxidation pathways of cyclic alkanes in a photochemical flow tube reactor. Oxidation products are collected on filters and analyzed by a novel soft ionization two-dimensional gas chromatography/mass spectrometry technique. The analysis reveals that the first-generation functionalization products (cholestanones, cholestanals, and cholestanols) are the dominant reaction products that account for up to 70% by mass of the total speciated compounds. The ratio of first-generation carbonyls to alcohols is near unity at every oxidation level. Among the cholestanones/cholestanals, 55% are found to have the carbonyl group on the rings of the androstane skeleton, while 74% of cholestanols have the hydroxyl group on the rings. Particle-phase oxidation products with carbon numbers less than 27 (i.e., "fragmentation products") and higher-generation functionalization products are much less abundant. Carbon bond cleavage was found to occur only on the side chain. Tertiary-carbon alkoxy radicals are suggested to play an important role in governing both the distribution of functionalization products (via alkoxy radical isomerization and reaction with oxygen) and the fragmentation products (via alkoxy radical decomposition). These results provide new insights into the oxidation mechanism of cyclic alkanes.


Humidification of inspired gases during mechanical ventilation.
Humidification of inspired gas is mandatory for all mechanically ventilated patients to prevent secretion retention, tracheal tube blockage and adverse changes occurring to the respiratory tract epithelium. However, the debate over "ideal" humidification continues. Several devices are available that include active and passive heat and moisture exchangers and hot water humidifiers Each have their advantages and disadvantages in mechanically ventilated patients. This review explores each device in turn and defines their role in clinical practice.


Group C beta-hemolytic streptococcal endocarditis: report of a pediatric case.
A 9-year-old boy with a ventricular septal defect and a bicuspid aortic valve developed bacterial endocarditis due to group C streptococci. He responded to an initial antibiotic regimen of nafcillin plus gentamicin and was cured by the use of penicillin G following the isolation of the organism. The unusual nature of this case is discussed and physicians are cautioned to recognize this organism as a potential cause of infectious endocarditis in the pediatric population.


Coronary artery disease: assessment with a comprehensive MR imaging protocol--initial results.
A comprehensive magnetic resonance (MR) imaging protocol for assessment of coronary artery disease (CAD) is presented. The protocol includes multiphase gradient-echo cine MR imaging for assessment of cardiac function, first-pass myocardial perfusion imaging at rest and during adenosine stress, MR imaging with delayed contrast enhancement for assessment of myocardial viability, and coronary MR angiography with a three-dimensional respiratory navigator-gated technique. In 10 patients, the protocol was completed in 61.5 minutes +/- 5.5 and yielded high image quality and diagnostic accuracy. This protocol may provide an integrated noninvasive screening tool for patients with CAD.


Retrospective analysis of one-stage maxillary sinus augmentation with endosseous implants.
The aim of the present retrospective study was to evaluate the results of a one-stage reconstructive procedure using titanium implants placed in iliac corticocancellous bone blocks grafted to the floor of maxillary sinuses. Forty-nine patients received 314 Brånemark implants, of which 171 implants of various lengths were placed in the grafted bone and 143 implants in the adjacent maxillary alveolar process (which includes 11 implants placed in onlay grafts). Five patients also received onlay grafts to the anterior maxilla. Follow-up time was 3 to 49 months after abutment connection, which was performed 9 months after implant placement. Eighty-two percent of the implants were successfully integrated in the grafted area and 84.8% in the adjacent bone. Eleven patients (22.4%) lost one to four implants or a few implants in strategic positions, requiring secondary implant placement prior to the manufacturing of fixed prostheses, whereas 35 (71.4%) received primary fixed restorations. Only two individuals (4.1%) received permanent implant-supported overdentures. Assessments of esthetics, phonetics, and function were made by the surgical-prosthodontic team and compared with those of the patients. Opinions regarding the functional outcome of treatment appeared least correlated. The total implant survival rate compares favorably with other reports.


[Plasma exchanges (author's transl)].
Therapeutic plasma exchanges (PE) represent a new approach to the management of numerous immune diseases and are in full development. In practice, however, they require sophisticated equipment, heavy investments and fully trained staff, and they are not as free from dangers as was initially assumed. A rational appraisal of the results therefore is desirable, but prospective comparative studies are scarce, and the present indication all too often rest upon non-scientific criteria, such as the need to slow down the course of an allegedly severe disease or the subjective impressions of the therapeutic team. In spite of these uncertainties, it would seem that PE deserves a major place in the treatment of diseases due to auto-antibodies or circulating immune complexes, as well as in that of malignant monoclonal gammapathies with hyperviscosity of the blood, some acute or chronic metabolic disorders and occasional intoxications with substances highly bound to serum proteins, which constitute the usual indications. The indications proposed in this review paper are based on the most representative publications in this particular field and on the own experience of the authors, who have performed 1200 PEs between 1978 and 1980.


Continuous Renal Replacement Therapy with the Adsorbing Filter oXiris in Septic Patients: A Case Series.
Extracorporeal treatment may be useful during sepsis, but definitive recommendations are lacking. Aim of this study is to review retrospectively the medical records of septic patients submitted to continuous renal replacement therapy (CRRT) with the adsorbing membrane oXiris and evaluate (1) the safety of the device, (2) the cardiorenal response, and (3) the immunological response. The medical records of 60 septic patients submitted to CRRT with the membrane oXiris from April 2011 to December 2018 have been reviewed. The adsorbing membrane oXiris® (Baxter, IL, USA) was used through a Prisma plataform (Prismaflex - Baxter, IL, USA). At basal time (T0), at 24 h (T1), and at the end of the treatment (T2) were analyzed the clinical data, the cytokines, and the time course of endotoxin. Sixty patients were included in the study. In total, 85% of patients had acute kidney injury (AKI). Every CRRT treatment was of 72 ± 13 h, with the consumption of 3.2 ± 1 filters. No AE events were reported. The main cardiorenal and respiratory parameters improved with a decrease of the noradrenaline dosage. Cytokines, procalcitonin, and endotoxin activity assay decreased too. SOFA total improved from 12.4 ± 2 to 9 ± 2. In sepsis/septic shock patients with AKI, CRRT with the adsorbing membrane oXiris may be safe and improves the cardiorenal - function and the clinical condition. The effect on cytokines and endotoxin may explain in part these results. A RCT is warranted to confirm these data.


[Changes in expression of microRNA-221 and phosphatase and tension protein homologue in nerve stump after peripheral nerve injury].
To study the expressions of microRNA-221 (miR-221) and the protein of phosphatase and tension protein homologue (PTEN) in the proximal and distal stumps after sciatic nerve injury in rats and their correlation with the repair of peripheral nerve injury, so as to provide a new target for clinical diagnosis of peripheral nerve injury. Ninety-six male Sprague-Dawley rats of SPF grade were selected to establish sciatic nerve injury models. Twenty-four rats were sacrificed at 0 (immediately after operation), 1, 4, and 7 days after operation. The proximal and distal sciatic nerve fragments were taken under aseptic conditions. The expression of miR-221 was detected by real-time fluorescent quantitative PCR, and the expression of PTEN protein was detected by Western blot and immunofluorescent staining. The relationship between miR-221 and PTEN was verified by dual-luciferase reporter gene. At the same time, the ultrastructure of nerve stump was observed by transmission electron microscopy. The results of real-time fluorescent quantitative PCR, Western blot, and immunofluorescence staining showed that the relative expression of miR-221 in the proximal and distal stumps increased gradually with time, and the relative expression of PTEN protein decreased gradually, and the differences between different time points after operation were significant ( P<0.05). At 1, 4, and 7 days after operation, the relative expression of miR-221 in proximal stump was significantly higher than that in distal stump, and the relative expression of PTEN protein in proximal stump was significantly lower than that in distal stump ( P<0.05). Dual-luciferase reporter gene suggested that PTEN was the target for miR-221. Transmission electron microscopy observation showed that the normal morphological structure was observed at 0 day after operation, and the proliferation of Schwann cells and degeneration of axons and myelin sheaths gradually increased with time. There was no significant difference between proximal and distal stumps at 1 day after operation. At 4 and 7 days, Schwann cells proliferated more in proximal stump than in distal stump, and the degeneration of axons and myelin sheaths was less. After sciatic nerve injury in rats, the up-regulation of the miR-221 expression targets the down-regulation of PTEN expression, which results in the difference of expression levels of miR-221 and PTEN in proximal and distal stumps. This phenomenon may play a role in promoting nerve repair after peripheral nerve injury.


[The status of herbal antilipemic agents].
A favourable effect on serum lipids may be achieved with herbal medicinal products, if they are administered at sufficient high dosages and sufficient long term use. Their efficacy is not so strong than that documented for chemically defined products, however their tolerability is superior. Maximal effects are more than that of a strong lipid lowering diet, however, lipid lowering herbal drugs are Allium sativum L., Cynara scolymus L., Curcumae longa L. All of them exert some more beneficial effects, which suggest to be an advantageous alternative for patients. This contribution gives a brief review and an assessment of the suitability of herbal medicinal preparations for the prophylactic or therapeutic treatment of hyperlipidemia and atherosclerosis.


Delayed reverse sural flap for staged reconstruction of the foot and lower leg.
Soft-tissue defects of the foot and lower leg caused by traumatic injury, tumor ablation, or infection associated with osteomyelitis often require coverage by flaps. One excellent option for reconstruction of these defects is the distally based neurofasciocutaneous sural flap. It allows rapid and reliable coverage of defects from the distal third of the lower leg to the forefoot without significant functional donor-site morbidity. However, the maximal size of the flap is limited by the delicate perfusion of the arterial network associated with the superficial sensory nerve. Delay procedures may increase the reliability of large sural flaps. The authors successfully used delayed sural flaps based on a two-step procedure for the treatment of 11 patients (three women and eight men, age 50.1 +/- 20.0 years) with osteomyelitis (n = 3), melanoma (n = 3), sarcoma (n = 1), squamous cell carcinoma (n = 1), posttraumatic defects (n = 2), and recurrent gouty ulcer (n = 1). The delay period ranged from 7 to 15 days (9.7 +/- 3.1), the length of the flap was from 9 to 19 (14.8 +/- 3.0) cm, and the width of the flap from 7 to 12 (9.2 +/- 1.3) cm. Temporary wound coverage was achieved by vacuum-assisted closure during the delay period. All defects were covered successfully without major complications. The delay procedure positively affects the viability of large sural neurofasciocutaneous flaps. The authors recommend this modification for patients with large defects at the distal third of the lower leg or foot, requiring a two-step surgical approach due to the underlying disease.


Characterization of flavonoid and naphthopyranone derivatives from Eriocaulon ligulatum using liquid chromatography tandem mass spectrometry.
Liquid chromatography-electrospray ionization multistage ion trap mass spectrometry (LC-ESI-IT-MS(n)) was used to analyze the secondary metabolites in the methanol extract of the capitulae of Eriocaulon ligulatum. The major components were mono- and diglycosides of flavonoids and naphthopyranones. Eleven compounds, including four new flavonol glycosides, were identified based on their fragmentation patterns in MS experiments and on NMR analysis of the isolated compounds. The described data may contribute to a better understanding of the taxonomic classification of the Eriocaulaceae family.


The population genetics of adaptation on correlated fitness landscapes: the block model.
Several recent theoretical studies of the genetics of adaptation have focused on the mutational landscape model, which considers evolution on rugged fitness landscapes (i.e., ones having many local optima). Adaptation in this model is characterized by several simple results. Here I ask whether these results also hold on correlated fitness landscapes, which are smoother than those considered in the mutational landscape model. In particular, I study the genetics of adaptation in the block model, a tunably rugged model of fitness landscapes. Considering the scenario in which adaptation begins from a high fitness wild-type DNA sequence, I use extreme value theory and computer simulations to study both single adaptive steps and entire adaptive walks. I show that all previous results characterizing single steps in adaptation in the mutational landscape model hold at least approximately on correlated landscapes in the block model; many entire-walk results, however, do not.


Management of intoxicated patients - a descriptive outcome analysis of 4,267 ICU patients.
Intoxications are common in intensive care units (ICUs). The number of causative substances is large, mortality usually low. This retrospective cohort study aims to characterize differences of intoxicated compared to general ICU patients, point out variations according to causative agents, as well as to highlight differences between survivors and non-survivors among intoxicated individuals in a large-scale multi-center analysis. A total of 105,998 general ICU patients and 4,267 individuals with the admission diagnoses "overdose" and "drug toxicity" from the years 2014 and 2015 where included from the eICU Collaborative Research Database. In addition to comparing these groups with respect to baseline characteristics, intensive care measures and outcome parameters, differences between survivors and non-survivors from the intoxication group, as well as the individual groups of causative substances were investigated. Intoxicated patients were younger (median 41 vs. 66 years; p<0.001), more often female (55 vs. 45%; p<0.001), and normal weighted (36% vs. 30%; p<0.001), whereas more obese individuals where observed in the other group (37 vs. 31%; p<0.001). Intoxicated individuals had a significantly lower mortality compared to general ICU patients (1% vs. 10%; aOR 0.07 95%CI 0.05-0.11; p<0.001), a finding which persisted after multivariable adjustment (aOR 0.17 95%CI 0.12-0.24; p<0.001) and persisted in all subgroups. Markers of disease severity (SOFA-score: 3 (1-5) vs. 4 (2-6) pts.; p<0.001) and frequency of vasopressor use (5 vs. 15%; p<0.001) where lower, whereas rates of mechanical ventilation where higher (24 vs. 26%; p<0.001) in intoxicated individuals. There were no differences with regard to renal replacement therapy in the first three days (3 vs. 4%; p=0.26). In sensitivity analysis (interactions for age, sex, ethnicity, hospital category, maximum initial lactate, mechanical ventilation, and vasopressor use), a trend towards lower mortality in intoxicated patients persisted in all subgroups. This large-scale retrospective analysis indicates a significantly lower mortality of intoxicated individuals compared to general ICU patients.


Approximate Optimal Tracking Control of Nondifferentiable Signals for a Class of Continuous-Time Nonlinear Systems.
In this article, for a class of continuous-time nonlinear nonaffine systems with unknown dynamics, a robust approximate optimal tracking controller (RAOTC) is proposed in the framework of adaptive dynamic programming (ADP). The distinguishing contribution of this article is that a new Lyapunov function is constructed, by using which the derivative information of tracking errors is not required in computing its time derivative along with the solution of the closed-loop system. Thus, the proposed method can make the system states follow nondifferentiable reference signals, which removes the common assumption that the reference signals have to be continuous for tracking control of continuous-time nonlinear systems in the literature. The theoretical analysis, simulation, and application results well illustrate the effectiveness and superiority of the proposed method.


Gastric cancer development after Helicobacter pylori eradication therapy: a new form of gastric neoplasia.
Along with the widespread use of eradication for Helicobacter pylori (H. pylori), the incidence of gastric cancer after eradication has also been increasing. There is a need for clarification of the clinical and biological characteristics of these neoplasms. We studied 27 cases of gastric cancer that developed after eradication (group AE). Out of the 27, we selected 26 with early-stage gastric cancer and compared them with 78 age-matched gastric cancer patients with H. pylori infection (group Pos) and 20 patients without H. pylori (group Neg). The patient with autoimmune gastritis was not included. Clinicopathological features, mucus patterns and Wnt5a expressions were compared among these groups. Among group AE patients, there were more males than females, and the tumor histology was mainly intestinal type, a significant difference from group Neg. In contrast, macroscopically, the tumors were predominantly of the flat-depressed type, a feature similar to that of group Neg but significantly different from that of group Pos. MUC2 and Wnt5a expression was significantly lower in group AE than in group Pos. Gastric cancer development after eradication may have a carcinogenic pathway similar to that in cancer with H. pylori infection, though macroscopic/biological features may be modified by eradication therapy.


Serum miR-372 is a Diagnostic and Prognostic Biomarker in Patients with Early Colorectal Cancer.
Circulating microRNAs are novel and non-invasive tumor biomarkers for colorectal cancer (CRC) detection. In this study, we investigated miR-372 expression in serum and tissues in CRC and colorectal precancerous lesions (CPL) patients by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Our data demonstrated that serum or tissue miR-372 levels were significantly up-regulated in patients with CRC or CPL, compared to healthy control (HC) subjects or normal tissues (P<0.05). High miR-372 expression in early colorectal cancer (ECRC) tissues were statistically significantly associated with tumor size (P<0.05), Tumor-Nodes-Metastasis (TNM) stage (P<0.05), and led to a worse overall survival (P=0.012). Postoperative serum miR-372 levels in ECRC patients significantly dropped, compared to the corresponding preoperative levels (P<0.05). The AUC of serum miR-372 expression for ECRC diagnosis was 0.854, which was significantly higher than that of combined tumor markers (CEA, CA19-9 and CA12-5) (0.613) (P<0.05). The sensitivity and specificity of serum miR-372 expression for ECRC diagnosis were 81.9 % and 73.3 %. All these findings provided an evidence that serum miR-372 could be a noninvasive biomarker for the early detection and prognosis of CRC.


Using electronic questionnaires to collect patient reported history.
EMR adoption has faced a major barrier around time and effort required to enter clinical data. In addition, patient entered data has not been effectively used by clinicians to identify critical clinical issues and drive best clinical interventions. By allowing patients to enter historical clinical data, using online questionnaires before their visit, it will have a positive impact on office workflow, physician and patient satisfaction, and support population based health and risk assessment.


Calibration of the angular dependence of the amide proton-C alpha proton coupling constants, 3JHN alpha, in a globular protein. Use of 3JHN alpha for identification of helical secondary structure.
The vicinal amide proton-C alpha proton spin-spin coupling constants, JHN alpha, in the globular protein basic pancreatic trypsin inhibitor (BPTI) have been measured using phase-sensitive correlated spectroscopy at high digital resolution. In conjunction with the crystal structure of BPTI, these data were used to calibrate the correlation between 3JHN alpha and the dihedral angle phi. The resulting "BPTI curve" is 3JHN alpha = 6.4 cos2 theta - 1.4 cos theta + 1.9 (theta = [phi - 60 degrees]). It is further shown that measurement of the spin-spin couplings 3JHN alpha presents an independent, reliable method for identification of the location of helical structure in the amino acid sequence of proteins.


Apoptosis-inducing activities of Halopteris scoparia L. Sauvageau (Brown algae) on cancer cells and its biosafety and antioxidant properties.
The aim of this study was to reveal the biological activities and in vivo toxicity profiles of n-hexane, chloroform and methanol extracts of brown algae Halopteris scoparia L. Sauvageau. In this study, extracts were tested for their phytochemical contents and antioxidant activities. The cytotoxic activities of the extracts against cervical adenocarcinoma (HeLa), colon colorectal adenocarcinoma (CaCo-2) and breast adenocarcinoma (MCF7) cells were assessed by MTT assay and total RNAs derived from cell lines to analyze gene expression were analyzed by Real Time Ready Human Apoptosis Panel 96. Also, in vivo toxicity and irritation effects of extracts were evaluated by LD50 acute toxicity test and Hen's egg test chorioallantoic membrane (HET-CAM) assay, respectively. Our results showed that the phenolic and flavonoid contents were determined only in methanol extract (33.20 ± 1.41 mg GAE/g and 1.26 ± 0.95 mg QE/g). Also, n-hexane has a broader spectrum of content than methanol and chloroform extracts. Furthermore, n-hexane extract in DPPH and methanol extract in ABTS+ exhibited the best antioxidant activity. In addition, MTT results revealed that each three extracts cause a significant reduction in cell viability, especially in HeLa cells. When the apoptotic gene expressions were examined after treatment of extracts, the expression of many pro-apoptotic genes in both caspase-independent and caspase-dependent intrinsic and extrinsic pathways increased. These findings suggest that, considering that it had not led to irritation and toxicity in vivo, edible H. scoparia is a natural antioxidant and its apoptotic/cytotoxic activities can potentially be used against human cancers.


Acute versus marginal deficiencies of nutrients.
Under experimental conditions, an acute nutrient deficiency (e.g., thiamin or folic acid) can be induced in both animal and human subjects. The signs and pathologic changes of an acute deficiency, however, may differ substantially from those seen clinically; often marginal deficiencies have been maintained over a long period of time.


Selective even-numbered bromination of triptycene tris(thiadiazoles).
An unusual even-numbered bromination of triptycene tristhiadiazole is described, giving selectively dibromo-, tetrabromo-, and hexabromotriptycenes with two bromines each at the same phenyl ring. The new compounds can be used as precursors for extended π-conjugated systems and polymers.


[Influence of electroacupuncture and capsaicin treatment on AChE activity and [3H]-QNB binding sites in the spinal dorsal horn].
1.5% Capsaicin (Cap) or Vehicle was respectively used to treat the right or left sciatic nerve in 20 Sprague-Dawley rats. On the seventh day, the 20 rats were at random divided into electroacupuncture (EA) group and non-EA group, the spinal cord corresponding to the afferent segments of sciatic nerve was taken out for observing the changes of acetylcholinesterase (AChE) activity and [3H]-quinuelidinylbenzylate (QNB) binding sites in the spinal dorsal horn (SDH). The results were as follows: (1) EA "Huantiao" could enhance AChE activity in the SDH and decrease [3H]-QNB binding sites; (2) Cap treating sciatice nerve could weaken AChE activity in the SDH and merease [3H]-QNB binding sites; (3) Cap treatment could inhibit or partially inhibit the actions of EA as above. The results indicated that ACh participated in the primary afferent of acupuncture information and might exist in Cap-sensitive neurons.


Bleaching of leaf litter and associated microfungi in subboreal and subalpine forests.
Fungal decomposition of lignin leads to the whitening, or bleaching, of leaf litter, especially in temperate and tropical forests, but less is known about such bleaching in forests of cooler regions, such as boreal and subalpine forests. The purposes of the present study were to examine the extent of bleached area on the surface of leaf litter and its variation with environmental conditions in subboreal and subalpine forests in Japan and to examine the microfungi associated with the bleaching of leaf litter by isolating fungi from the bleached portions of the litter. Bleached area accounted for 21.7%-32.7% and 2.0%-10.0% of total leaf area of Quercus crispula and Betula ermanii, respectively, in subboreal forests, and for 6.3% and 18.6% of total leaf area of B. ermanii and Picea jezoensis var. hondoensis, respectively, in a subalpine forest. In subboreal forests, elevation, C/N ratio and pH of the FH layer, and slope aspect were selected as predictor variables for the bleached leaf area. Leaf mass per area and lignin content were consistently lower in the bleached area than in the nonbleached area of the same leaves, indicating that the selective decomposition of acid unhydrolyzable residue (recalcitrant compounds such as lignin, tannins, and cutins) enhanced the mass loss of leaf tissues in the bleached portions. Isolates of a total of 11 fungal species (6 species of Ascomycota and 5 of Basidiomycota) exhibited leaf-litter-bleaching activity under pure culture conditions. Two fungal species (Coccomyces sp. and Mycena sp.) occurred in both subboreal and subalpine forests, which were separated from each other by approximately 1100 km.


Fast and accurate leaf verification for dynamic multileaf collimation using an electronic portal imaging device.
A prerequisite for accurate dose delivery of IMRT profiles produced with dynamic multileaf collimation (DMLC) is highly accurate leaf positioning. In our institution, leaf verification for DMLC was initially done with film and ionization chamber. To overcome the limitations of these methods, a fast, accurate and two-dimensional method for daily leaf verification, using our CCD-camera based electronic portal imaging device (EPID), has been developed. This method is based on a flat field produced with a 0.5 cm wide sliding gap for each leaf pair. Deviations in gap widths are detected as deviations in gray scale value profiles derived from the EPID images, and not by directly assessing leaf positions in the images. Dedicated software was developed to reduce the noise level in the low signal images produced with the narrow gaps. The accuracy of this quality assurance procedure was tested by introducing known leaf position errors. It was shown that errors in leaf gap as small as 0.01-0.02 cm could be detected, which is certainly adequate to guarantee accurate dose delivery of DMLC treatments, even for strongly modulated beam profiles. Using this method, it was demonstrated that both short and long term reproducibility in leaf positioning were within 0.01 cm (1sigma) for all gantry angles, and that the effect of gravity was negligible.


Positron emission tomography with [18F]fluorodeoxyglucose improves staging and patient management in patients with head and neck squamous cell carcinoma: a multicenter prospective study.
PURPOSE To address the impact of positron emission tomography with [(18)F]fluorodeoxyglucose (PET-FDG) on the initial staging and management of patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS This multicenter, prospective study included 233 patients with newly diagnosed and untreated HNSCC. TNM stage and therapeutic decision were first determined based on the conventional work-up (including physical examination, computed tomography [CT]/magnetic resonance imaging of the head and neck region, and thoracic CT) and sealed in envelope 1. Whole-body PET-FDG was then performed, and subsequent TNM stage and therapeutic decision were written in envelope 2. Changes in TNM stages and in patient management as a result of PET-FDG imaging were recorded. Clinical outcome and histopathology were used as gold standards to validate the TNM stage. Conventional and PET stages were compared using the McNemar test. Results Conventional and PET stage were discordant in 100 (43%) of 233 patients. PET proved to be accurate in 47 patients and inaccurate in 13 patients. TNM status was left unconfirmed in 40 patients because no therapeutic change was expected from the stage difference. Conventional + PET TNM classification (envelope 2) was significantly more accurate than conventional classification (envelope 1; P < .0001, McNemar test). PET-FDG altered the therapeutic plan in 32 (13.7%) of 233 patients. CONCLUSION Adding whole-body PET-FDG to the pretherapeutic conventional staging of HNSCC improved the TNM classification of the disease and altered the management of 13.7% of patients. These findings support the implementation of PET-FDG in the routine imaging work-up of HNSCC.


Understanding global transition assessments.
Several methods currently used for determining meaningful or important change in health-related quality of life (HRQoL) measures are anchored by global transition items. It can be empirically demonstrated that patients' responses to these gold standards for change do not adequately incorporate the prior condition, yet these transition items play an influential role in patient-clinician communications and cannot be disregarded. This follow-up study queried patients to better understand how they ascertained their transition assessments. Prior to their qualitative interviews, the 41 participants in this study had completed 1 year of enrollment in a clinical study with bi-monthly HRQoL telephone interviews that included the SF-36 and a disease-specific HRQoL instrument (asthma, COPD, or heart disease), as well as global transition assessments for each instruments domains. We used face-to-face cognitive interview and the think aloud approaches to obtain qualitative clues for understanding patient reports of HRQoL changes over time. Interview transcripts were coded using the four components of the Rapkin-Schwarz Appraisal Model: frame of reference; sampling strategy; standards of comparison; and combinatory algorithm. Patients' explanations for determining global transition item responses often focused on current mobility and fatigue patterns, physicians' statements about their conditions, comparisons of their current states with the prior health conditions, and strong personal convictions that reflected a resistance to voicing any emotional changes. Patients also expressed primary health concerns, like back pain, that were not related to the chronic conditions (asthma, COPD or heart disease) under investigation. HRQoL studies and patient-clinician communications that incorporate global transition assessments to anchor the interpretations of HRQoL changes should also consider additional relevant questions to understand the process patients uses to appraise and report changes in HRQoL.