Dimethyl Sulfoxide Prevents Radiation-Induced Oral Mucositis Through Facilitating DNA Double-Strand Break Repair in Epithelial Stem Cells.
Oral mucositis is one of the most prevalent side effects in patients undergoing radiation therapy for head and neck cancers. Current therapeutic agents such as palifermin recombinant human keratinocyte growth factor and amifostine do not efficiently or fully prevent mucositis. Dimethyl sulfoxide (DMSO), a free-radical scavenger, has shown therapeutic benefits in many preclinical and clinical studies. This study aimed to investigate the efficacy of DMSO in a clinically relevant mouse model of acute, radiation-induced oral mucositis. Oral mucositis was induced by a high single and fractioned irradiation of the head and neck area in C57BL/6J mice, and the effects of DMSO (by intraperitoneal injection) were assessed by macroscopic and histopathological examination. Epithelial stem and progenitor cells were analyzed by immunohistochemical staining of p63 and Ki-67, and DNA double-strand breaks (DSBs) were visualized by immunofluorescence detection of γ-H2AX. Tumor xenograft was obtained using CAL-27 cells. Pretreatment with DMSO protected the oral mucosa from severe acute radiation injury, reduced the extent of radiation-induced weight loss, and had no significant effects on tumor weight in irradiated or nonirradiated xenograft mice. Furthermore, the efficacy of DMSO was superior to that of recombinant human keratinocyte growth factor and amifostine. DMSO treatment prevented the loss of proliferative lingual epithelial stem and progenitor cells upon irradiation. More interestingly, the average levels of γ-H2AX foci were significantly decreased in p63-positive epithelial stem cells at 6 hours, but not at 2 hours, after irradiation, indicating that DMSO facilitated DNA DSB repair rather than suppressing the indirect action of irradiation. DMSO prevents the loss of proliferative lingual epithelial stem and progenitor cells upon irradiation by facilitating DNA DSB repair, thereby protecting against radiation-induced mucositis without tumor protection. Given its high efficacy and low toxicity, DMSO could be a potential treatment option to prevent radiation-induced oral mucositis.


Intra-Individual Consistency in Endocrine Profiles Across Successive Pregnancies.
It is yet unknown how similar women's hormone levels are during successive pregnancies, and very little is known about the degree to which siblings experience similar prenatal environments. Given the importance of understanding how women's reproductive life histories exert cumulative effects on health via hormone exposure, and the importance of understanding how fetal programming via endocrine signaling affects sibling trait concordance, here, we address this important lacuna in the literature. This study aimed to investigate how consistent women's hormone profiles are across two successive pregnancies. This longitudinal, prospective study followed a cohort of 28 women across two pregnancies (PREG 1 and PREG 2). Women's circulating hormone levels were assessed from blood samples at 25, 31, and 37 weeks' gestation for adrenocorticotropic hormone (ACTH), placental corticotropin-releasing hormone (pCRH), cortisol, estradiol, and progesterone. ACTH and cortisol levels were assessed 3 months postpartum. Research questions include: Are hormone levels in PREG 2 significantly different from levels in PREG 1? What proportion of variance in PREG 2 hormone levels is attributable to variance in PREG 1 levels? Are hormone levels more stable between PREG 1 and PREG 2 compared with postpartum phases following these pregnancies? Is pCRH, which is completely placentally derived, less similar than other hormones across successive pregnancies? Pregnant women attended study visits at a university psychobiology laboratory in Southern California. Comparisons of hormone concentrations across women's successive pregnancies via paired t test revealed substantial consistency from one pregnancy to another, with only significant differences between pregnancies for pCRH. Regressions revealed substantial predictability from one pregnancy to another, with between 17-56% of PREG 2 variances accounted for by PREG 1 values. Women exhibited lower degrees of consistency and predictability in hormone levels across postpartum phases compared with gestational concentrations. This is the first study to describe maternal and placental hormone levels across successive pregnancies.


Clinical trials: Renewed attention to the interpretation of the P values--review.
The P values tell us the chance of making a type I error of finding a difference where there is none. In the 1970s, exact P values were laborious to calculate and were generally approximated from statistical tables, in the form of P < 0.01 or 0.05 < P < 0.10, etc. In the past decades with the advent of computers, it became easy to calculate exact P values such as 0.84 or 0.007. The cut-off P values have not been completely abandoned, but broader attention is given to the interpretation of the exact P values. This article reviews standard and renewed interpretations of P values. (1) Standard interpretation of cut-off P values such as P < 0.05: The null hypothesis of no difference can be rejected on the limitations/assumptions that we have up to a 5% chance of a type I error of finding a difference where there is none, we have 50% chance of a type II error of finding no difference where there is one, the data are normally distributed, they follow exactly the same distribution as that of the population from which the sample was taken. (2) A common misunderstanding of the P value: It is actually the chance that the null hypothesis is true and consequently that a P > 0.05 indicates a significant similarity in the data. P > 0.05 may indeed indicate similarity. However, a study sample too small or study design inadequate to detect the difference must be considered. (3) Renewed interpretations of the P values: Exact P values enable more refined conclusions from the research than cut-off levels. Instead of concluding significantly yes/no, we are able to consider levels of probabilities from very likely to be true to very likely to be untrue. Very large P values are not compatible with a normal gaussian frequency distribution; very small P values do not completely confirm prior expectations. They must be scrutinized and may have been inadequately improved.


Evaluation of percutaneous annuloplasty for treatment of functional mitral regurgitation: A retrospective study.
The management of severe functional mitral regurgitation (FMR) in patients with heart failure (HF) and low ejection fraction is controversial, but percutaneous transcatheter procedures are promising. In this retrospective analysis, we aimed to assess the efficacy of the Carillon Mitral Contour System in patients with "inoperable" severe FMR. Seventy three patients (mean age 66.89, range 31-90 years) with congestive heart failure (CHF), severe FMR, and reduced ejection fraction (<35%) who underwent Carillon device implantation were examined. The study group consisted of patients with successfully implanted devices whereas the control group comprised patients in whom the device could not be deployed. The primary endpoint was combined all-cause mortality and first hospitalization for HF (whichever came first). The median (Q1, Q3) follow-up was 31 (11-49) months. The device was deployed successfully in 50 patients (implant group) and not in 23 patients (non-implant group). Both the primary endpoint and all-cause mortality were lower in the "implant" group, but the differences were not significant. The median to primary endpoint was 21 [95% confidence interval (CI) 8.8-33.2] and six (95% CI 0.1-11.9) months for the implant group and the non-implant group, respectively (p=0.078). Carillon Mitral Contour System implantation is a safe procedure and results in the reduction of all-cause mortality and combined endpoint of mortality and hospitalizations for HF in inoperable patients with severe FMR and low ejection fraction, although the difference did not meet the significance level.


Insulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72).
While insulin resistance (IR) is associated with specific metabolite signatures in adults, there have been few truly longitudinal studies in healthy children, either to confirm which abnormalities are present, or to determine whether they precede or result from IR. Therefore, we investigated the association of serum metabolites with IR in childhood in the Earlybird cohort. The Earlybird cohort is a well-characterized cohort of healthy children with annual measurements from age 5 to 16 years. For the first time, longitudinal association analyses between individual serum metabolites and homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR) have been performed taking into account the effects of age, growth, puberty, adiposity, and physical activity. IR was higher in girls than in boys and was associated with increasing body mass index (BMI). In longitudinal analysis IR was associated with reduced concentrations of branched-chain amino acids (BCAA), 2-ketobutyrate, citrate and 3-hydroxybutyrate, and higher concentrations of lactate and alanine. These findings demonstrate the widespread biochemical consequences of IR for intermediary metabolism, ketogenesis, and pyruvate oxidation during normal child growth and development. Longitudinal analysis can differentiate metabolite signatures that precede or follow the development of greater levels of IR. In healthy normal weight children, higher levels of IR are associated with reduced levels of BCAA, ketogenesis, and fuel oxidation. In contrast, elevated lactate concentrations preceded the rise in IR. These changes reveal the metabolite signature of insulin action during normal growth, and they contrast with previous findings in obese children and adults that represent the consequences of IR and obesity.


"Lock and Key" and "Induced-Fit" Host-Guest Models in Two Digold(I)-Based Metallotweezers.
Two different metallotweezers, each with two pyrene-imidazolylidene-gold(I) arms, were used as hosts for a series of planar aromatic guests. The metallotweezer with a dibenzoacridinebis(alkynyl) spacer (1) orients the two pyrene-imidazolylidene-gold(I) arms in a parallel disposition, with an interpanel distance of about 7 Å. The second metallotweezer (2) contains a carbazolylbis(alkynyl) spacer that directs the two pyrene panels in a diverging orientation. Determination of the association constants via 1H NMR titrations demonstrates that the binding strength shown by 1 is significantly larger than that found by 2, with binding affinities as large as 104 M-1 (in CDCl3), for the encapsulation of N,N'-dimethylnaphthalenetetracarboxydiimide with 1. The differences in the binding affinities are due to binding models associated with formation of the related host-guest complexes. While 1 operates via a "lock and key" model, in which the host does not suffer distortions upon formation of the inclusion complex, 2 operates via a guest-induced fit model. The large association constants shown by 1 with two planar guests were used for promotion of the template-directed synthesis of 1, which in the absence of an external template is produced in an equimolecular mixture with its self-aggregated congener, clippane [12]. This observation strongly suggests that the mechanically interlocked clippane is formed through a self-template-directed mechanism, while bonds are broken/formed during the synthetic protocol.


Navigating the cervical cancer screening guidelines for women aged older than 65 years.
One of the most notable changes stemming from consensus guidance in 2012 is cessation of cervical cancer screening in low-risk women aged older than 65 years. Despite evidence provided for this recommendation, implementation in clinical practice can be challenging, with resistance from patients and providers. This NAMS Practice Pearl reviews data supporting this recommendation and provides clinicians with confidence as we counsel our patients.


Activation of the A(3) adenosine receptor suppresses superoxide production and chemotaxis of mouse bone marrow neutrophils.
Adenosine is formed in injured/ischemic tissues, where it suppresses the actions of essentially all cells of the immune system. Most of the anti-inflammatory actions of adenosine have been attributed to signaling through the G(s) protein-coupled A(2A) adenosine receptor (AR). Here, we report that the A(3)AR is highly expressed in murine neutrophils isolated from bone marrow. Selective activation of the A(3)AR with (2S,3S,4R,5R)-3-amino-5-[6-(2,5-dichlorobenzylamino)purin-9-yl]-4-hydroxytetrahydrofuran-2-carboxylic acid methylamide (CP-532,903) potently inhibited mouse bone marrow neutrophil superoxide generation and chemotaxis induced by various activating agents. The selectivity of CP-532,903 was confirmed in assays using neutrophils obtained from A(2A)AR and A(3)AR gene "knockout" mice. In a model of thioglycollate-induced inflammation, treating mice with CP-532,903 inhibited recruitment of leukocytes into the peritoneum by specifically activating the A(3)AR. Collectively, our findings support the theory that the A(3)AR contributes to the anti-inflammatory actions of adenosine on neutrophils and provide a potential mechanistic explanation for the efficacy of A(3)AR agonists in animal models of inflammation (i.e., inhibition of neutrophil-mediated tissue injury).


Investigation of the prognostic value of coexpressed erbB family members for the survival of colorectal cancer patients after curative surgery.
Epidermal growth factor receptor (EGFR), erbB2, erbB3 and erbB4 are four transmembrane glycoproteins belonging to the subtype I tyrosine kinases. They share structure homologies and are believed to direct cellular growth through the ligand-stimulated tyrosine phosphorylation of intracellular substrate. The overexpression of these tyrosine kinases has been linked to various cancers. To examine the role of the erbB family in the neoplastic transformation of the human colon, we analysed the protein expression of these four members by immunohistochemistry in paraffin-embedded specimens from 125 resected colorectal cancers. Our data showed that for EGFR expression, 62 (50%) were scored as '+', and 2 (2%) as '++'. For erbB2 expression, 39 (31%) were classified as '+', and 5 (4%) as '++'. For erbB3 expression, 43 (34%) were scored as '+', and 3 (2%) as '++'. A significantly higher percentage of overexpressed erbB3 was observed in early stage carcinomas (Dukes' stage A or B) (50%) than in advanced stage cancers (Dukes' stage C or D) (15%) (P<0.0001). For erbB4 expression, 22 (18%) were scored as '+', and 5 (4%) as '++'. Early stage patients had a lower percentage of erbB4 overexpression than the late stage ones (18% versus 28%). Concomitant overexpression of erbB2 and erbB3 occurred in 21% (16/78) of the early stage carcinomas, whereas it occurred in only 2% (1/47) of the late stage ones (P=0.003). Conversely, simultaneous overexpression of erbB2 and erbB4 occurred in 17% (8/47) of the late stage carcinomas but in only 4% (3/78) of the early stage ones (P=0.02). Overexpression of EGFR, erbB2, erbB3 or erbB4 alone was not significantly associated with a shortened survival. However, patients with a simultaneous overexpression of erbB2 and erbB4 had a shorter overall survival time than others in the univariate analysis (P=0.01). This significance disappeared after adjustment for Dukes' staging in the Cox model. In conclusion, overexpressed erbB3 was common in early stage colorectal cancers, but its prevalence was significantly reduced in late stage ones. The percentage of its coexpression with erbB2 was significantly higher in early stage than in late-stage cancers. Heterodimerisation between erbB2 and erbB4 may play a role in the late stages of carcinogenesis.


Ambiguities in Powder Indexing: the Impact of a Quaternary Lattice Metric Singularity on the Characterization of Mawsonite and Chatkalite.
A lattice metric singularity occurs when unit cells defining two (or more) lattices yield the identical set of unique calculated d-spacings. The minerals Mawsonite and Chatkalite are of especial interest as both are characterized by tetragonal unit cells that correspond to the second member of a quaternary lattice metric singularity. This singularity includes lattices that are Cubic I, Tetragonal P, Orthorhombic F, and Orthorhombic P. The Mawsonite and Chatkalite lattices are unique in that they are highly specialized. In each case: (1) the determinative c/a ratio is very near 1/√2, (2) the symmetrical scalars of the reduced form [ a · a : b · b : c · c = 1:2:2] have greater specialization than required for the given reduced form type, (3) the tetragonal lattice has derivative lattices of higher symmetry, and (4) the powder pattern is highly compressed. Mawsonite and Chatkalite serve as exemplar-type compounds. Their tetragonal structure has important implications in structure determination using powder diffraction data. First, any cubic I lattice - established solely on the basis of indexing procedures - may actually be tetragonal or orthorhombic. Second, in establishing the lattice of an unknown, results from powder data indexing require routine confirmation by other techniques (e.g., single crystal, optical, etc.).


Optical studies of high-temperature superconducting cuprates.
The optical studies of high-temperature superconducting cuprates (HTSC) are reviewed. From the doping dependence of room temperature spectra, a dramatic change of the electronic state from a Mott (charge transfer) insulator to a Fermi liquid has been revealed. Additionally, the unusual 2D nature of the electronic state has been found. The temperature dependence of the optical spectra provided a rich source of information on the pseudogap, superconducting gap, Josephson plasmon, transverse Josephson plasma mode and precursory superconductivity. Among these issues, Josephson plasmons and transverse Josephson plasma mode were experimentally discovered by optical measurements, and thus are unique to HTSC. The effect of the spin/charge stripe order is also unique to HTSC, reflecting the conducting nature of the stripe order in this system. The pair-breaking due to the stripe order seems stronger in the out-of-plane direction than in the in-plane one.


[Significance of periosteum interposition in epiphysiolysis].
The periosteum interposition in epiphysiolysis does not lead to growth disorder, as has been shown in follow-up studies on 22 cases. The cortical, partial pseudarthrosis, which is caused by the periosteum interposition, heals and then changes into a bone scar, as could be proved histologically in rabbits.


Acoustic neuroma (vestibular schwannoma): surgical results on 240 patients operated on dorsal decubitus position.
To evaluate the result of the surgical treatment of vestibular schwannoma (VS) operated in dorsal decubitus (mastoid position). 240 patients with a VS underwent a retrosigmoid craniotomy for tumor resection in dorsal decubitus (mastoid position). The function of 7th and 8th cranial nerves was monitored during surgery and the opened internal auditory canal (IAC) was reconstructed using a vascularized dura flap, muscle and fibrin glue. Complete tumor removal was achieved in 99% of the cases, with a mortality of 1.6%. The facial nerve function was preserved in 85% of cases and hearing in 40% of the patients (with preoperative hearing) with tumors of up 1.5 cm in diameter. The incidence of cerebrospinal fluid leak was 5.8% and meningitis 2.9%. Venous air embolism was registered in 3% of cases; it was not associated to mortality. Surgical removal of VS in dorsal position has several advantages; the morbidity and mortality are very low.


Dissipative quantum dynamics with the surrogate Hamiltonian approach. A comparison between spin and harmonic baths.
The dissipative quantum dynamics of an anharmonic oscillator coupled to a bath is studied with the purpose of elucidating the differences between the relaxation to a spin bath and to a harmonic bath. Converged results are obtained for the spin bath by the surrogate Hamiltonian approach. This method is based on constructing a system-bath Hamiltonian, with a finite but large number of spin bath modes, that mimics exactly a bath with an infinite number of modes for a finite time interval. Convergence with respect to the number of simultaneous excitations of bath modes can be checked. The results are compared to calculations that include a finite number of harmonic modes carried out by using the multiconfiguration time-dependent Hartree method of Nest and Meyer [J. Chem. Phys. 119, 24 (2003)]. In the weak coupling regime, at zero temperature and for small excitations of the primary system, both methods converge to the Markovian limit. When initially the primary system is significantly excited, the spin bath can saturate restricting the energy acceptance. An interaction term between bath modes that spreads the excitation eliminates the saturation. The loss of phase between two cat states has been analyzed and the results for the spin and harmonic baths are almost identical. For stronger couplings, the dynamics induced by the two types of baths deviate. The accumulation and degree of entanglement between the bath modes have been characterized. Only in the spin bath the dynamics generate entanglement between the bath modes.


Electrical Spin Orientation, Spin-Galvanic, and Spin-Hall Effects in Disordered Two-Dimensional Systems.
In disordered systems, the hopping conductivity regime is usually realized at low temperatures where spin-related phenomena differ strongly from the cases of delocalized carriers. We develop the unified microscopic theory of current-induced spin orientation, spin-galvanic, and spin-Hall effects for the two-dimensional hopping regime. We show that the corresponding susceptibilities are proportional to each other and determined by the interplay between the drift and the diffusion spin currents. Estimations are made for realistic semiconductor heterostructures using the percolation theory. We show that the electrical spin polarization in the hopping regime increases exponentially with the increase of the concentration of localization sites and may reach a few percent at the crossover from the hopping to the diffusion conductivity regime.


Characterization of a S-adenosyl-l-methionine (SAM)-accumulating strain of Scheffersomyces stipitis.
S-adenosyl-l-methionine (SAM) is an important molecule in the cellular metabolism of mammals. In this study, we examined several of the physiological characteristics of a SAM-accumulating strain of the yeast Scheffersomyces stipitis (M12), including SAM production, ergosterol content, and ethanol tolerance. S. stipitis M12 accumulated up to 52.48 mg SAM/g dry cell weight. Proteome analyses showed that the disruption of C-24 methylation in ergosterol biosynthesis, a step mediated by C-24 sterol methyltransferase (Erg6p), results in greater SAM accumulation by S. stipitis M12 compared to the wild-type strain. A comparative proteome-wide analysis identified 25 proteins that were differentially expressed by S. stipitis M12. These proteins are involved in ribosome biogenesis, translation, the stress response, ubiquitin-dependent catabolic processes, the cell cycle, ethanol tolerance, posttranslational modification, peroxisomal membrane stability, epigenetic regulation, the actin cytoskeleton and cell morphology, iron and copper homeostasis, cell signaling, and energy metabolism.


Effect of damaged vehicle evacuation on traffic flow with open boundaries.
The effects of the damaged car evacuation (P(exit)) and the collision (P(col)) probabilities on the traffic flow behavior of a car accident are investigated in the one-dimensional cellular automaton Nagel-Schreckenberg model, with injecting (alpha) and extracting (beta) rates in parallel dynamics. In this study, we suppose that the car involved in collision is evacuated from the road, with an exit probability P(exit). It is found that the behaviors of density, current, and (alpha,beta) phase diagram topology depend strongly on the values of P(exit) and P(col). Indeed, the high-density region shrinks when increasing P(exit). Moreover, the critical value alpha(c)(beta), at which the low-density-high-density transition occurs, increases when increasing P(col) and/or P(exit). Furthermore, the critical value at which the transition high-density-low-density occurs decreases when increasing beta and increases with alpha.


Assessment of Classical and Non-Classical Quantitative Electroencephalographic Measures in Patients with Substance Use Disorders.
Background: People diagnosed with substance use disorders (SUDs) are at risk for impairment of brain function and structure. However, physicians still do not have any clinical biomarker of brain impairment that helps diagnose or treat these patients when needed. The most common method to study these patients is the classical electroencephalographic (EEG) analyses of absolute and relative powers, but this has limited individual clinical applicability. Other non-classical measures such as frequency band ratios and entropy show promise in these patients. Therefore, there is a need to expand the use of quantitative (q)EEG beyond classical measures in clinical populations. Our aim is to assess a group of classical and non-classical qEEG measures in a population with SUDs. Methods: We selected 56 non-medicated and drug-free adult patients (30 males) diagnosed with SUDs and admitted to Rehabilitation Clinics. According to qualitative EEG findings, patients were divided into four groups. We estimated the absolute and relative powers and calculated the entropy, and the alpha/(delta + theta) ratio. Results: Our findings showed a significant variability of absolute and relative powers among patients with SUDs. We also observed a decrease in the EEG-based entropy index and alpha/(theta + delta) ratio, mainly in posterior regions, in the patients with abnormal qualitative EEG. Conclusions: Our findings support the view that the power spectrum is not a reliable biomarker on an individual level. Thus, we suggest shifting the approach from the power spectrum toward other potential methods and designs that may offer greater clinical possibilities.


Endoscopic Management of Gastrointestinal Leaks and Perforation with Polyglycolic Acid Sheets.
Gastrointestinal (GI) leakage, fistulae, and perforations can be serious and life threatening. There has been a paradigm shift in the management approach of these conditions, from surgical to conservative, including endoscopic management. Here, we report two cases of endoscopic closure of a GI fistula and perforation using polyglycolic acid (PGA) sheets with fibrin glue. The first case is of an anastomotic leak detected after subtotal gastrectomy with gastroduodenostomy. After failed application of endoclips, a PGA sheet was applied, and the fistula was successfully closed. The second case was of a 15-mm large perforated gastric ulcer, which was also successfully closed with a PGA sheet. This is the first case report that PGA sheet was used for the treatment of overt perforation. The outcome of these cases suggest that endoscopic closure using PGA sheets can be considered as a useful alternative for the management of GI leakage, fistulae, and perforations.


Are medication effects on subjective response to alcohol and cue-induced craving associated? A meta regression study.
Alcohol administration and cue-reactivity paradigms are frequently used to screen for the initial efficacy of medications for alcohol use disorder (AUD). While medication effects on the primary outcomes for these paradigms are assumed to be qualitatively related, there is a critical lack of quantitative evidence to support this hypothesis. The study aims to test the relationship between medication effect sizes on subjective response to alcohol administration and medication effect sizes for cue-induced craving to cue exposure, using meta-analysis. Systematic literature searches were conducted to identify randomized trials, wherein AUD medications were tested using the alcohol administration and/or cue-reactivity paradigms. From these studies, descriptive statistics were collected to compute medication effect sizes on the primary outcomes for each respective paradigm. With medication as the unit of analysis, medication effect sizes in alcohol administration studies were compared with medication effect sizes in cue-reactivity studies using the Williamson-York regression which allows for meta-regression across independent samples. Medication effect sizes on alcohol-induced stimulation and alcohol-induced craving were not significantly associated with medication effect sizes on cue-induced alcohol craving (k stimulation = 10 medications, [Formula: see text] and k craving = 11 medications, [Formula: see text] (SE = 0.237), [Formula: see text]), respectively. Medication effect sizes on alcohol-induced sedation were significantly associated with medication effects on cue-induced craving (k = 10 medications, [Formula: see text] (SE = 0.258), [Formula: see text]), such that medications that increased alcohol-induced sedation were more likely to reduce cue-induced alcohol craving. With the exception of alcohol-induced sedation, there is little quantitative evidence of medication effects on subjective response domains measured during alcohol administration parallel medication effects on cue-induced alcohol craving. To provide additional context to the current study, future work should examine whether cue-reactivity findings predict clinical trial outcomes.


Seed coat colour of Indian mustard [Brassica juncea (L.) Czern. and Coss.] is associated with Bju.TT8 homologs identifiable by targeted functional markers.
Seed coat colour is an important trait in Indian mustard. Breeding for seed coat colour needs precise knowledge of mode of inheritance and markers linked to it. The present study was focussed on genetics and development of functional markers for seed coat colour. F1s (direct and reciprocal) and F2 populations were developed by crossing two contrasting parents for seed coat colour (DRMRIJ-31, brown seeded and RLC-3, yellow seeded). Phenotypic results have shown that the seed coat colour trait was under the influence of maternal effect and controlled by digenic-duplicate gene action. Further, Bju.TT8 homologs of both parents (DRMRIJ-31 and RLC-3) were cloned and sequenced. Sequencing results of Bju.TT8 homologs revealed that in RLC-3, gene Bju.ATT8 had an insertion of 1279bp in the 7th exon; whereas, gene Bju.BTT8 had an SNP (C→T) in the 7th exon. These two mutations were found to be associated with yellow seed coat colour. Using sequence information, functional markers were developed for both Bju.TT8 homologs, validated on F2 population and were found highly reliable with no recombination between the markers and the phenotype. Further, these markers were subjected to a germplasm assembly of Indian mustard, and their allelic combination for the seed coat colour genes has been elucidated. The comparative genomics of TT8 genes revealed high degree of similarity between and across the Brassica species, and the respective diploid progenitors in tetraploid Brassica species are the possible donors of TT8 homologs. This study will help in the marker-assisted breeding for seed coat colour, and aid in understanding seed coat colour genetics more precisely.


Roentgenologic findings of the hydrolethalus syndrome.
The hydrolethalus syndrome is an autosomal recessive malformation syndrome which has been recently described in Finland. The name hydrolethalus refers to the main findings, namely polyhydramnios, hydrocephalus and lethality. The patients are either stillborn or die soon after birth. The typical roentgenologic findings are hypoplasia of the tibia associated with the anomalies of the respective bone ray, e.g. metatarsus primus varus atavisticus, hallux varus or hallux duplex varus and hydrocephalus with extreme micrognathia and a specific midline defect of the occipital bone.


Chinese herbal medicine combined with cognitive-behavioural therapy for avoidant paruresis: a controlled trial.
Avoidant paruresis is a common clinical condition in urology and psychosomatic medicine. However, it has limited treatment options that are safe and effective with few side effects. Our study aimed to investigate the effectiveness and safety of the Chinese herbal Yangxin Tongquan decoction combined with cognitive-behavioural therapy (CBT) for avoidant paruresis. Sixty-eight patients with avoidant paruresis were divided into a treatment group (33 patients) and a control group (35 patients). The control group was assigned 10 weeks of CBT and systematic desensitisation. In addition to CBT and systematic desensitisation, the treatment group was given the Chinese herbal Yangxin Tongquan decoction during the 10-week study. The Shy Bladder Syndrome Scale (SBS) and the Self-rating Anxiety Scale (SAS) were administered before and after treatment to measure any change. The overall efficacy in the treatment group (n=30) was 80.0% vs 62.5% in the control group (n=33). Comparing pretreatment and post-treatment measures, both groups showed improvement in SBS scores and SAS scores (treatment group: t(SBS) =8.397, p(SBS) <0.001, t(SAS) =8.216, p(SAS)<0.001; control group: t(SBS) =6.802, p(SBS) <0.001, t(SAS)=5.171, p(SAS) <0.001). Moreover, both groups' SBS and SAS scores changed significantly over time (SBS scores: Ftime =118.299, p<0.001; SAS scores: Ftime =92.114, p<0.001). However, the treatment group performed better than the control group (SBS scores: Ftime*group =5.709, p=0.020; SAS scores: Ftime*group =7.235, p=0.009). The Chinese herbal Yangxin Tongquan decoction combined with cognitive-behavioural psychotherapy positively affects the treatment of avoidant paruresis without significant adverse effects.


Rehabilitation after heart transplantation: the Australian experience.
This study was designed to assess aspects of the quality of life and rehabilitation of heart transplant recipients who had transplantations at St. Vincent's Hospital, New South Wales, Australia, between February 1984 and March 1987. Factors determining return to full-time employment were delineated. A questionnaire was sent to 51 recipients. The response rate was 92%. The questionnaire measured employment status and satisfaction with family, social, marital, and sexual life. Financial status, exercise ability, and participation in daily activities were also assessed. Analysis showed that 53% of recipients had returned to either full-time or part-time employment, home duties, or full-time study. A further 28% were receiving a pension, 9% had chosen voluntary retirement, 6% were receiving unemployment benefits, and 4% were getting paid leave. Ability to exercise was improved for 77% of recipients and remained the same for another 14%. Financial status was unchanged for 45% and improved for 17%. Thirty-eight percent believed that they were worse off financially. Ratings of social, family, and marital life showed nearly complete or complete satisfaction in most cases. Satisfaction with sex life was less favorable. Comparison of the group who had returned to full-time employment with the group receiving a pension identified two variables of work status--length of time since transplantation and employment status before transplantation. There were also some differences between the two groups on quality of life ratings.


A Highly Robust Silicon Ultraviolet Selective Radiation Sensor Using Differential Spectral Response Method.
This paper presents a silicon ultraviolet radiation sensor with over 90% UV internal quantum efficiency (QE) and high selectivity to the UV waveband without using optical filters. The sensor was developed for applications that require UV measurement under strong background visible and near-infrared (NIR) lights, such as solar UV measurement, UV-C monitoring in greenhouses or automated factories, and so on. The developed sensor is composed of monolithically formed silicon photodiodes with different spectral sensitivities: a highly UV responsive photodiode with internal quantum efficiency (QE) of nearly 100% for UV light, and a lowly UV responsive photodiode with UV internal QE lower than 10%. The photodiodes were optimized to match their visible and NIR light responsivity, and the UV signal is extracted from the background radiation by using the differential spectral response method. With this approach, an internal QE of over 90% for UV light was obtained, with a residual internal QE to non-UV light lower than 20% for 400 nm, 5% for 500 nm, 2% for 600 nm and 0.6% to NIR light. The developed sensor showed no responsivity degradation after exposure towards strong UV light. It was confirmed by the simulation results that the residual responsivity is further suppressed by employing an on-chip band-rejection optical layer consisting of several layers of silicon oxide and silicon nitride films.


Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids.
There were already several epidemiologic studies that showed eating fish frequently seemed to reduce deaths from coronary heart disease. There were also observational and clinical trials that more specifically showed that the reduction in cardiovascular deaths from eating fish was largely the result of the prevention of sudden cardiac death by n-3 polyunsaturated fatty acids in fish oil. This led me to perform a clinical trial in which all subjects had an implanted cardioverter-defibrillator and were at very high risk of sudden cardiac death. The results of this study and the mechanisms by which n-3 fish oil fatty acids prevent fatal cardiac arrhythmias will be the subject of this review.


Research on the screening mechanisms of composite vibrating screens based on discrete elements.
To strengthen the screening efficiency of traditional vibrating screens, a new type of vibrating screen, namely the composite vibrating screen, has been proposed based on the Lissajous vibration synthesis theory. The working principles of composite vibrating screens have been explained. Numerical simulations of the sieving processes for such composite vibrating screens were carried out using the discrete element method. Compared with traditional linear vibrating screens, the force, stratification mechanisms, and throwing principles of the material on the screen's surface were studied, and the vibrating screens' material transportation and screening efficiency were analyzed. The results showed that with the existence of xyz three directions sub-vibrations of the composite vibrating screens, the material particle group is more diversified by the forces, the particle system is loose, the stratification effects are adequate, and the material is evenly distributed on the screen surfaces. Under the same vibration parameters, the composite vibrating screens' screening efficiencies and material transportation capacities were better than those of linear vibrating screens. This work provides a necessary reference for the development and application of new composite vibrating screens.


Vernal keratoconjunctivitis in school children in Rwanda: clinical presentation, impact on school attendance, and access to medical care.
We sought to describe the clinical presentation, effect on visual acuity, impact on school attendance, and access to appropriate eye care in children with vernal keratoconjunctivitis (VKC) in Rwanda (Central Africa). Case-control study nested within a cross-sectional survey. We examined 3041 children; 121 had VKC. Primary schools were randomly selected and children were interviewed using a questionnaire on VKC-related symptoms. Data on health-seeking behavior and school attendance were recorded. Children received a full eye examination, including visual acuity using a LogMar E Chart. Description of the clinical findings, unaided visual acuity, prior attendance for medical eye care, and the impact of VKC on school attendance. Of the 121 children with VKC, 119 (98.4%) had only limbal disease. Ocular itching (n = 101; 83.5%) was the predominant symptom and this was seasonal in 66 children (65.4%), constant but with variable intensity in 18 (17.8%), and constant with constant intensity in 17 children (16.8%). Children with VKC were >6 times more likely to have corneal astigmatism >2 diopters in their worse eye (odds ratio [OR], 6.31; 95% confidence interval [CI], 3.26-12.26; P<0.001) than controls. Eight affected eyes had astigmatism >4 diopters or irregular astigmatism incompatible with autokeratometry. Although 4 eyes (1.7%) had uncorrected low vision from VKC-induced corneal astigmatism or keratoconus, only 1 child was visually impaired in both eyes. School nonattendance for an ocular reason during the last 3 months was 5 times more likely in children with VKC (n = 44; 36.4%) than among those without (n = 297; 10.2%; OR, 5.04; 95% CI, 3.40-7.47; P < 0.001). Repeating a school year or having ever dropped out of school was not more common among children with VKC than those without. Medical eye care had been sought by 54 (44.6%) children with VKC. This survey of prevalence and treatment of VKC in an African community adds to the argument for better primary eye care, including a safe topical medication. Long-term follow-up of this cohort is required to ascertain the overall risk of sight-threatening complications.


Evaluation of fungal and bacterial contaminations of patient-used ocular drops.
The aim of the present study was to investigate the incidence of fungal and bacterial contaminations of in-use eye drop products in the teaching department of ophthalmology, Imam Khomeini Hospital, Ahvaz. Two hundred and eighty seven eye drop bottles were randomly collected at the end of day 1, day 2, day 3, day 4 and day 7 of use. The eye drop residues, swabs from internal caps and droppers were inoculated onto MacConkey agar, blood agar and Sabouraud's dextrose agar. The identification of the recovered organisms was accomplished using standard microbial identification techniques. The incidence of microbial contamination of in-use eye drop products was 17.8%, with the highest rate (24.6%) and the lowest rate (9.0%) noted with day 1 and day 3 samples, respectively. The most contaminated part of the eye drop products was the caps (45.9%) followed by droppers (41.0%) and residual contents (13.1%). Considering mendicants contents, those with pilocarpine (41.7%) had the highest rate of contamination followed by atropine (31.8%), tropicamide (28.6%) and betamethasone (23.3%). Our study revealed the potential risk of contamination of in-use eye drop products in hospitals, but we did not find a direct relationship between usage duration and contamination rate.


Functionality and Cell Senescence of CD4/ CD8-Selected CD20 CAR T Cells Manufactured Using the Automated CliniMACS Prodigy® Platform.
Clinical studies using autologous CAR T cells have achieved spectacular remissions in refractory CD19+ B cell leukaemia, however some of the patient treatments with CAR T cells failed. Beside the heterogeneity of leukaemia, the distribution and senescence of the autologous cells from heavily pretreated patients might be further reasons for this. We performed six consecutive large-scale manufacturing processes for CD20 CAR T cells from healthy donor leukapheresis using the automated CliniMACS Prodigy® platform. Starting with a CD4/CD8-positive selection, a high purity of a median of 97% T cells with a median 65-fold cell expansion was achieved. Interestingly, the transduction rate was significantly higher for CD4+ compared to CD8+ T cells and reached in a median of 23%. CD20 CAR T cells showed a good specific IFN-γ secretion after cocultivation with CD20+ target cells which correlated with good cytotoxic activity. Most importantly, 3 out of 5 CAR T cell products showed an increase in telomere length during the manufacturing process, while telomere length remained consistent in one and decreased in another process. In conclusion, this shows for the first time that beside heterogeneity among healthy donors, CAR T cell products also differ regarding cell senescence, even for cells manufactured in a standardised automated process.


[Quantitative and qualitative determination of lactic acid in fecal filtrate in children].
The authors describe qualitative and quantitative methods for lactic acid assessment in children's feces. A total of 102 children with mainly lactose intolerance were examined. Benedict's test with feces filtrate, lactose tolerance test, and measurements of fecal carbohydrates were used in the diagnostic investigations. Mean lactic acid levels made up (mean +/- m) 33.3 +/- 3.6 mmol/l (6.3 +/- 1.0 in healthy infants on breast feeding and 6.0 +/- 1.3 mmol/l in those on mixed and formula feeding). Fecal carbohydrate levels were normal (below 5 g/l) in 12 infants, but lactic acid levels made up 67.8 +/- 6.1 mmol/l. Qualitative reaction to lactic acid in feces, starting from 44.4 mmol/l, was detected in 27% of infants. Differences in the values of healthy children and those with lactic carbohydrate intolerance were found significant (p < 0.001).


Ligase detection reaction for the analysis of point mutations using free-solution conjugate electrophoresis in a polymer microfluidic device.
We have developed a new method for the analysis of low abundant point mutations in genomic DNA using a combination of an allele-specific ligase detection reaction (LDR) with free-solution conjugate electrophoresis (FSCE) to generate and analyze the genetic products. FSCE eliminates the need for a polymer sieving matrix by conjugating chemically synthesized polyamide "drag-tags" onto the LDR primers. The additional drag of the charge-neutral drag-tag breaks the linear scaling of the charge-to-friction ratio of DNA and enables size-based separations of DNA in free solution using electrophoresis with no sieving matrix. We successfully demonstrate the conjugation of polyamide drag-tags onto a set of four LDR primers designed to probe the K-ras oncogene for mutations highly associated with colorectal cancer, the simultaneous generation of fluorescently labeled LDR/drag-tag conjugate (LDR-dt) products in a multiplexed, single-tube format with mutant:WT ratios as low as 1:100, respectively, and the single-base, high-resolution separation of all four LDR-dt products. Separations were conducted in free solution with no polymer network using both a commercial capillary array electrophoresis (CAE) system and a PMMA microchip replicated via hot-embossing with only a Tris-based running buffer containing additives to suppress the EOF. Typical analysis times for LDR-dt were 11 min using the CAE system and as low as 85 s for the PMMA microchips. With resolution comparable to traditional gel-based CAE, FSCE along with microchip electrophoresis decreased the separation time by more than a factor of 40.


Nitric oxide regulation of glyceraldehyde-3-phosphate dehydrogenase activity in Dictyostelium discoideum cells and lysates.
The ability of compounds releasing nitric oxide (NO) to regulate glyceraldehyde-3-phosphate dehydrogenase (GraPDH) activity was analysed both in cell homogenates and in intact Dictyostelium discoideum. The time course of GraPDH inactivation in cell lysates by NO-releasing compounds suggests that two processes may be involved, one of which accounts for the majority of the inactivation and shows a close correlation with GraPDH ADP-ribosylation. Maximal ADP-ribosylation under these conditions exhibited a stoichiometry of about 0.4 mol ADP-ribose/mol enzyme tetramer. NO-mediated inhibition of GraPDH activity was attenuated if specific substrates, cofactors, or cysteine were added to cytosol preparations. Under such conditions, ADP-ribosylation of the enzyme was correspondingly reduced or negligible. Intact cells treated with NO-releasing compounds were shown to respond by rapidly decreasing their GraPDH activity. This inhibition was transient and, after a 10-min incubation, enzyme activity returned to the level seen in control cells. The time course of these in vivo changes correlated well with those of the NO-stimulated ADP-ribosylation of GraPDH also seen in intact cells. The basis underlying the NO-stimulated inhibition of GraPDH activity was investigated and found to reflect a decreased Vmax. No changes in either the Km of the enzyme for its substrates or its state of polymerization were observed.


Nutritional assessment and antioxidant activities of different varieties of Vigna radiata.
Three cultivars of Vigna radiata, namely, NM-92, NM-98, and NM-06, were analyzed for their proximate composition. The samples were also tested by HPLC for amino acid content. The data showed that all the varieties had same moisture level. The maximum ash content (4.29%) was present in NM-92, and crude fat (2.26%) was highest in NM-98 while NM-06 contained maximum amount of crude protein. About eighteen types of amino acids were detected in each of the three varieties. Acidic amino acids, that is, aspartic and glutamic acids, were in considerable amount ranged from 13 to 23% followed by leucine, isoleucine, alanine, valine, lysine, phenyl alanine, serine, and arginine which fell in the range of 3-8% of total protein. The maximum amount (13.00 and 22.80%) of aspartic and glutamic acids was present in NM-98. Similarly arginine (6.83%) and serine (5.45%) were also in highest amount in this variety. Leucine (7.46%) was maximum in NM-92 variety. NM-06 contained almost all the amino acids in lesser quantity except for few like threonine, proline, glycine, and alanine. It was concluded from the present study that varieties were of different nutritional value and HPLC was a sensitive method for amino acids determination. Antioxidant activities of all three varieties were also assayed and showed significant results.


Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.
The human COL11A1 gene has been shown to be up-regulated in stromal cells of colorectal tumours, but, so far, the immunodetection of procollagen 11A1, the primary protein product of COL11A1, has not been studied in detail in human colon adenocarcinomas. Some cancer-associated stromal cells seem to be derived from bone marrow mesenchymal cells; the expression of the COL11A1 gene and the parallel immunodetection of procollagen 11A1 have not been evaluated in these latter cells, either. We used quantitative RT-PCR and/or immunocytochemistry to study the expression of DES/desmin, VIM/vimentin, ACTA2/αSMA (alpha smooth muscle actin) and COL11A1/procollagen 11A1 in HCT 116 human colorectal adenocarcinoma cells, in immortalised human bone marrow mesenchymal cells and in human colon adenocarcinoma-derived cultured stromal cells. The immunodetection of procollagen 11A1 was performed with the new recently described DMTX1/1E8.33 mouse monoclonal antibody. Human colon adenocarcinomas and non-malignant colon tissues were evaluated by immunohistochemistry as well. Statistical associations were sought between anti-procollagen 11A1 immunoscoring and patient clinicopathological features. Procollagen 11A1 was immunodetected in human bone marrow mesenchymal cells and in human colon adenocarcinoma-associated spindle-shaped stromal cells but not in colon epithelial or stromal cells of the normal colon. This immunodetection paralleled, in both kinds of cells, that of the other mesenchymal-related biomarkers studied: vimentin and alpha smooth muscle actin, but not desmin. Thus, procollagen 11A1(+) adenocarcinoma-associated stromal cells are similar to "activated myofibroblasts". In the series of human colon adenocarcinomas here studied, a high procollagen 11A1 expression was associated with nodal involvement (p = 0.05), the development of distant metastases (p = 0.017), and advanced Dukes stages (p = 0.047). The immunodetection of procollagen 11A1 in cancer-associated stromal cells could be a useful biomarker for human colon adenocarcinoma characterisation.


Cisplatin monotherapy with concurrent radiotherapy versus combination of cisplatin and 5-fluorouracil chemotherapy with concurrent radiotherapy in patients with locoregionally advanced cervical carcinoma.
To compare the efficacy, toxicity and survival of cisplatin monotherapy with concurrent radiotherapy ver-sus combination of cisplatin and 5-fluorouracil (5-FU) with concurrent external beam radiotherapy (EBRT) in patients with locoregionally advanced cervical carcinoma FIGO stages IIB-IV. 134 patients with locoregionally advanced, histologically confirmed carcinoma of the uterine cervix were analysed. The first group of patients (n=70; 52.24%) started concomitant chemotherapy on the second day of radiotherapy with single-agent cisplatin 40 mg/m(2) given 2 h before radiotherapy, once a week for 6 courses. The second group of patients (n=64; 47.76%) started concomitant chemotherapy on the second day of radiotherapy with cisplatin 75 mg/m(2). Treatment was continued with 96-h infusion of 5-FU 4 g/m(2) (1 g/ m(2) per day for 5 consecutive days). The patients were irradiated by EBRT followed by intracavitary brachytherapy (ICB). 24- and 42-month survival in the first group were 71.9 and 57.81% and 52.5 and 35.4% in the second group, respectively (p=0.012). Mean time to progression in the first group was 24 months and in second group it was 15.9 months (p=0.012). After 2 years progression was noted in 38.3% of the first and in 62.9% of second group patients (p=0.003). After 40 months 60 patients were without relapse, 35 (57.81%) patients in the first group and 25 (37.147percnt;) patients in the second group (p=0.018). Treatment with combined cisplatin and 5-FU with concurrent EBRT was more efficient in comparison to cisplatin monotherapy with concurrent radiotherapy in patients with locoregionally advanced cervical carcinoma, in terms of 12- and 24-month overall survival and disease relapse after 2 years.


Myeloablative unrelated cord blood transplantation for acute leukemia patients between 50 and 55 years of age: single institutional retrospective comparison with patients younger than 50 years of age.
Increasing recipient age is a well-known risk factor for graft-versus-host disease (GVHD) and treatment-related mortality (TRM) and has a negative impact on allogeneic hematopoietic stem cell transplantation. Since the incidence of severe GVHD after cord blood transplantation (CBT) is lower than that after transplants using bone marrow or mobilized peripheral blood grafts from adult cells, we should expect better outcomes from CBT in older patients. To evaluate the feasibility and efficacy of myeloablative unrelated CBT in patients aged between 50 and 55 years, we performed a retrospective comparison of 100 patients with acute leukemia who received cord blood grafts at our institution. Nineteen older patients (median age, 52; range, 50-55) and 81 younger patients (median, 36; range, 16-49) received a myeloablative conditioning regimen including 12 Gy of total body irradiation and chemotherapy. GVHD prophylaxis included cyclosporine with (n = 96) or without (n = 4) methotrexate. There were no significant differences in the incidences of grades II to IV acute GVHD, extensive-type chronic GVHD, TRM, and the probability of overall and disease-free survival between these groups. These results suggest that, in patients with acute leukemia, myeloablative CBT might be as safe and effective in patients aged between 50 and 55 years as in younger patients.


[Features of autonomic regulation of the cardiovascular system in human late ontogenesis.]
Using the method of arterial piezopulsometry, statistical and spectral analyzes of variable parameters (VmaxPP and TNN) of pulse waves of blood pressure in patients aged 18 to 85 years were performed. The individual characteristics of the autonomous (vegetative and neuroendocrine) regulation of the muscular effectors (ME) of the cardiovascular system (CVS) in an elderly man (75 years old) and a young woman (20 years old) were estimated with high accuracy. These data, as well as the results of a comparative study of patients of different ages, made it possible to identify a certain pattern of directed change in the sympathoadrenal regulation of ME CVS in human ontogenesis. It is concluded that in the course of their lives, people undergo a restructuring of the physiological mechanism of the autonomous regulation of their ME CVS, aimed at replacing short-term sympathetic regulation in young people with more effective and more stable regulation by humoral catecholamines in elderly.


Single versus biplane right and left ventricular volumetry: a cast and clinical study.
True volume (y) and measured volume (x) determined from 23 right and 22 left normal human casts in four biplane angiographic positions and in their eight single-plane components were used to find the correction factor (b) by regression through the origin (y = bx). The correction factors were applied to human studies to assess the validity of the various biplane and single-plane modalities in vivo. The casts studies yield excellent correlations in both right and left biplane methods (right volumetry: 0.555 less than or equal to b less than or equal to 0.708, 0.917 less than or equal to r less than or equal to 0.954, 4.10 less than or equal to SEE less than or equal to 6.01 left volumetry: 0.748 less than or equal to b less than or equal to 0.825, 0.974 less than or equal to r less than or equal to 0.982, 4.81 less than or equal to SEE 5.79). Good results were obtained with single-plane volumetries as well (right volumetry: 0.316 less than or equal to b less than or equal to 0.887, 0.750 less than or equal to r less than or equal to 0.917, 10.75 less than or equal to SEE less than or equal to 18.96; left volumetry: 0.728 less than or equal to b less than or equal to 0.881, 0.897 less than or equal to r less than or equal to 0.976 5.73 less than or equal to SEE less than or equal to 11.97). The correction factors for the single-plane studies depend much more strongly on the spatial position relative to the radiographic system, particularly in the case of the right ventricular volumes. Thus, the application of the appropriate correction factors is mandatory. The human studies (141 left and 60 right volumetric studies in various single-plane and biplane projections) showed a larger scatter of single-plane values, more pronounced for the right ventricle. In certain disease conditions, single plane volumetric studies using cast-derived correction factors cannot be used to obtain meaningful results. Correction factors for the following single or biplane mode volumetry are presented for the first time: biplane hepatoclavicular view (right and left ventricle), biplane long axial oblique view (right ventricle), and their single-plane components; lateral and 60 degree Left Anterior Oblique (LAO) single plane for the left-sided measurements, Postero-Anterior (PA), lateral, and 60 degree LAO for the single-plane right-sided calculations.


Formation of stable transcription complexes as assayed by analysis of individual templates.
Conditions were established where transient transfection of two marker genes resulted in the expression of one or the other, but not both, in individual cells as assayed by immunofluorescence. Thus, the expression from a single cell reflects the activity of single active transcription templates. Under these conditions, a vector encoding the simian virus 40 large tumor antigen (SV40 T-Ag) driven by the SV40 enhancer and early promoter was transfected into CV-1, L, or HeLa cells yielding, for all three cell types, about 10-30% T-Ag-positive cells as assayed by immunofluorescence. Similar vectors containing either mutated or deleted SV40 enhancers also gave T-Ag-positive cells, but at about 1/100 the frequency. Quantitative analysis showed that T-Ag-positive cells produced about the same amount of T-Ag whether or not an active enhancer was present. Chloramphenicol acetyltransferase-encoding vectors gave the same result. The data are consistent with the hypothesis that at a low, but finite, probability, fully functional transcription complexes can form on a given active template in the absence of enhancer DNA. Enhancers seem to increase the number of active templates. Subcloning experiments suggest that these transcription complexes can be surprisingly stable.


Polymer chain dynamics in solution probed with a fluorescence blob model.
This Account describes a new fluorescence tool that characterizes the chain dynamics of polymers in solution. This new tool, coined the fluorescence blob model (FBM), is employed to analyze the fluorescence decays of polymers randomly labeled with pyrene. The FBM yields the number of monomers making up a blob (Nblob) where a blob is the volume probed by an excited pyrene. By establishing a relationship between Nblob and the lifetime of pyrene used as an internal clock, the FBM provides previously unavailable information about polymer chain dynamics and opens new venues of research, which are described in this Account.


Oral administration of berberine represses macrophage activation-associated benign prostatic hyperplasia: a pivotal involvement of the NF-κB.
Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in men over the age of 50. Clinical studies have suggested that chronic inflammation is associated with BPH pathoprogression. Berberine (BB) is a natural compound found in Berberis vulgaris, Coptis chinensis and Phellodendron amurense. Although several studies have documented that BB may be effective for inflammation, the effects of the oral administration of BB on BPH are not fully understood. The effects of BB on chronic prostatic inflammation were evaluated in a testosterone-induced BPH animal model. Orally administered BB alleviated the pathological alterations induced by BPH and significantly suppressed the expression of inflammatory markers while enhancing the expression of antioxidant factors. Furthermore, BB regulated the activation of macrophages via NF-κB signaling pathway inhibition in the BPH rat model. The effects and underlying signaling pathway of BB in RWPE-1 cells exposed to macrophage conditioned medium (CM) were also demonstrated in vitro. While CM stimulation induced prostatic cell proliferation and upregulated the expression of inflammatory factors, BB exerted anti-proliferation and anti-inflammatory effects in RWPE-1 cells. These findings propose that BB suppresses androgen-dependent BPH development by targeting NF-κB-mediated pro-inflammatory signaling.


Coordinated Dynamics of RNA Splicing Speckles in the Nucleus.
Despite being densely packed with chromatin, nuclear bodies and a nucleoskeletal network, the nucleus is a remarkably dynamic organelle. Chromatin loops form and relax, RNA transcripts and transcription factors move diffusively, and nuclear bodies move. We show here that RNA splicing speckled domains (splicing speckles) fluctuate in constrained nuclear volumes and remodel their shapes. Small speckles move in a directed way toward larger speckles with which they fuse. This directed movement is reduced upon decreasing cellular ATP levels or inhibiting RNA polymerase II activity. The random movement of speckles is reduced upon decreasing cellular ATP levels, moderately reduced after inhibition of SWI/SNF chromatin remodeling and modestly increased upon inhibiting RNA polymerase II activity. To define the paths through which speckles can translocate in the nucleus, we generated a pressure gradient to create flows in the nucleus. In response to the pressure gradient, speckles moved along curvilinear paths in the nucleus. Collectively, our results demonstrate a new type of ATP-dependent motion in the nucleus. We present a model where recycling splicing factors return as part of small sub-speckles from distal sites of RNA processing to larger splicing speckles by a directed ATP-driven mechanism through interchromatin spaces.


Structure of a neutralizing antibody bound monovalently to human rhinovirus 2.
The structure of a complex between human rhinovirus 2 (HRV2) and the Fab fragment of neutralizing monoclonal antibody (MAb) 3B10 has been determined to 25-A resolution by cryoelectron microscopy and three-dimensional reconstruction techniques. The footprint of 3B10 on HRV2 is very similar to that of neutralizing MAb 8F5, which binds bivalently across the icosahedral twofold axis. However, the 3B10 Fab fragment (Fab-3B10) is bound in an orientation, inclined at approximately 45 degrees to the surface of the virus capsid, which is compatible only with monovalent binding of the antibody. The canyon around the fivefold axis is not directly obstructed by the bound Fab. The X-ray structures of a closely related HRV (HRV1A) and a Fab fragment were fitted to the density maps of the HRV2-Fab-3B10 complex obtained by cryoelectron microscope techniques. The footprint of 3B10 on the viral surface is largely on VP2 but also covers the VP3 loop centered on residue 3064 and the VP1 loop centered on residue 1267. MAb 3B10 can interact directly with VP2 residue 2164, the site of an escape mutation on VP2, and with VP1 residues 1264 to 1267, the site of a deletion escape mutation. Deletion of these residues shortens the VP1 loop, moving it away from the MAb binding site. All structural and biochemical evidence indicates that MAb 3B10 binds to a conformation epitope on HRV2.


[Contribution of biological tests in the evaluation of professional asthma (author's transl)].
The eventual difficulties of diagnosing professional asthma sometimes need the help of methods of complementary diagnosis. The histamine-release test and that of basophils granules liberation are studied in this work, concerning 12 substances with a suspected allergenic action (saw-dust, textile fibres, chemicals, products of plant origin). The histamine-release and granules liberation tests were performed according to the techniques described respectively by Lichtenstein and Benveniste. Both examinations were positive in a concording manner in 8 cases out of 12, but this positivity was difficult to interprete for etiopathogenic reasons. The study of the curve of histamine-release in relation with the dose of allergen used in the test nevertheless enables to differentiate two types of answers, one related to an allergic mechanism, the other to an irritative one. These observations led to the deduction that a positive granules liberation test could be due to a non allergic mechanism. Negativity in both tests does not allow the rejection of the part played by these substances into the genesis of respiratory signs. Indeed these tests only investigate one part of the mechanisms which can be involved: direct stimulation of vagal irritant receptors and the plain pharmacological reactions escape from this type of biological investigations. The biological tests studied in this work can be used in a complementary fashion in the etiological survey of professional asthma but they cannot replace the realistic tests, more reliable because they react whatever the etiopathogenic mechanism involved.


Amiodarone--application and clinical pharmacology in atrial fibrillation and other arrhythmias.
Forty patients with atrial fibrillation (AF), 23 patients with ventricular extrasystoles (VES), and 11 patients with various arrhythmias (VA) were treated with amiodarone (0.2-0.6 g/day). Suppression of arrhythmia was 67.5% in AF, 78.2% in VES, and 81.8% in others with VA. Median age of converted patients was higher than that of nonconverted. The duration of AF before treatment was inversely related to drug efficacy. Average time needed for conversion was 6-8 days of treatment. Plasma amiodarone concentration at the day of conversion did not differ from that of nonconverted patients. Amiodarone concentration levels off after the 8th day of treatment, whereas that of the metabolite increases with time of treatment. Biologic half-life of plasma amiodarone after discontinuation of treatment varied, but was higher than 4 days. The percent of decline of the metabolite concentration was lower than that of the parent drug.


Superficial chemical peels.
Superficial chemical peeling (SCP) involves the application of a peeling agent to the skin, resulting in destruction of part or all of the epidermis. SCP is mainly recommended for facial rejuvenation, photoaging and superficial rhytides, pigmentary dyschromias and acne. It can be used on all Fitzpatrick skin types, no sedation is needed, and the desquamation is usually well accepted. Overpeel and complications are very rare. The most commonly used SCP agents are glycolic acid 20-70%, trichloroacetic acid 10-35%, Jessner's solution, salicylic acid, pyruvic acid, resorcinol 30-50% preparations, and solid carbon dioxide. The careful selection of patients is critical for the outcome of a SCP and contraindications must be seriously considered. The peel procedure is generally common for all SCP agents but a good knowledge of the specific characters of each agent is of great importance in order to decide which to use for each individual patient.


Bacteroides xylanisolvens possesses a potent anti-hyperuricemia effect in goslings fed on a high-protein diet.
Hyperuricemia is widespread in humans and birds which is a necessary physiological factor leading to gout. Studies have shown an inextricable relationship between gut microbiota and hyperuricemia. This study explored the association between intestinal flora and hyperuricemia in Goslings. The hyperuricemia model was established in gosling by a high protein diet (HPD). 16S rDNA sequencing showed that the cecal microbiota differed significantly between the HPD and control groups (fed with the normal protein). The abundance of Firmicutes was higher in the HPD group, while the Bacteroidetes were lower than in controls. To investigate the role of intestinal flora in hyperuricemia, the cecum microbiotas from the HPD group and the control group were transplanted to the newly born goslings by gavage. The serum uric acid levels of the goslings that transplanted the cecal microbiota of the HPD group were significantly higher than the goslings that transplanted the cecal microbiota of the controls. Furthermore, the transplantation of cecal microbiota also affects the production and excretion of uric acid in goslings. Then we identify the gut bacterium Bacteroides xylanisolvens as an effective anti-hyperuricemia in the Goslings. B. xylanisolvens reduces serum uric acid concentrations in hyperuricemia in the Goslings' model, and it can up-regulation ABCG2 mRNA expression in the kidney and down-regulation XDH mRNA expression in the liver. The intestinal flora acts as a novel target for the therapeutic approach to hyperuricemia and gout, suggest Bacteroides xylanisolvens is a possible route to therapy for hyperuricemia and gout in goslings.


High-performance liquid chromatography-electrospray ionization mass spectrometry determination of mitiglinide in human plasma and its pharmacokinetics.
A selective and sensitive method employing high-performance liquid chromatography-electrospray ionization mass spectrometry was developed and validated for the determination of mitiglinide in human plasma.With gliclazide as the internal standard, mitiglinide was extracted from plasma with n-hexane: = 80 : 20 (v/v). The organic layer was evaporated and the residue was redissolved in methanol: water (10 mM CH3COONH4, pH = 3.0) = 65 : 35 (v/v). An aliquot of 10 microl was chromatographically analyzed on a prepacked Shimadzu VP-ODS (5 microm, 150 x 2.0 mm i.d.) using the mobile phase comprising methanol: water (10 mM CH3COONH4) = 65 : 35 (v/v) by means of selected-ion monitoring mode mass spectrometry. Standard curves were linear (r2 = 0.9972) over the concentration range of 2.84-11 300 pmol/ml and had good accuracy and precision. The within- and between-batch precisions of the method were within 15% of standard deviation. The lower limit of detection was 1.42 pmol/ml. The validated HPLC/ESI-MS method has been successfully applied in the pharmacokinetics of mitiglinide in 12 healthy Chinese volunteers.


"Atopy patch tests" in the diagnosis of delayed food hypersensitivity.
The prevalence of atopic diseases is increasing worldwide. Food allergies are the earliest manifestation of atopy. Atopic eczema affects about 18% of infants in the first 2 years of life and the main cause is allergy to multiple foods. A strong association has been shown between atopic eczema and IgE mediated allergy to milk, egg or peanut, but more than two-thirds of patients intolerant to food proteins have no evidence of IgE sensitization to the relevant food protein. Recently, patch testing with proteins has been found to be helpful in diagnosing food allergy in cases where skin prick tests and estimation of specific antibodies have failed. The methodology of atopy patch test (APT) is unstandardized, and contradictory results have been reported. In contrast to the more standardized APT methodology with aeroallergens, the sensitivities and specificities of food allergens can easily be estimated with food challenge tests. With multiallergic children adding of APTs to the skin prick tests and specific antibody estimation tests give more information for planning a wide enough elimination diet to get the skin and gastrointestinal tract symptomless in order to perform the challenge test which remains the only reliable test for food allergy. Standardization of the APT materials and reading procedure will add to the reliability of this new test method.


Intrinsically disordered inhibitor of glutamine synthetase is a functional protein with random-coil-like pKa values.
The sequential action of glutamine synthetase (GS) and glutamate synthase (GOGAT) in cyanobacteria allows the incorporation of ammonium into carbon skeletons. In the cyanobacterium Synechocystis sp. PCC 6803, the activity of GS is modulated by the interaction with proteins, which include a 65-residue-long intrinsically disordered protein (IDP), the inactivating factor IF7. This interaction is regulated by the presence of charged residues in both IF7 and GS. To understand how charged amino acids can affect the binding of an IDP with its target and to provide clues on electrostatic interactions in disordered states of proteins, we measured the pKa values of all IF7 acidic groups (Glu32, Glu36, Glu38, Asp40, Asp58, and Ser65, the backbone C-terminus) at 100 mM NaCl concentration, by using NMR spectroscopy. We also obtained solution structures of IF7 through molecular dynamics simulation, validated them on the basis of previous experiments, and used them to obtain theoretical estimates of the pKa values. Titration values for the two Asp and three Glu residues of IF7 were similar to those reported for random-coil models, suggesting the lack of electrostatic interactions around these residues. Furthermore, our results suggest the presence of helical structure at the N-terminus of the protein and of conformational changes at acidic pH values. The overall experimental and in silico findings suggest that local interactions and conformational equilibria do not play a role in determining the electrostatic features of the acidic residues of IF7.


Nanophthalmic uveal effusion.
A nanophthalmic patient with hypermetropia, shortened anterior-posterior axial length, and thickened choroid presented with a choroidal detachment and nonrhegmatogenous retinal detachment (NRRD). He underwent partial thickness, 5 x 7 mm, sclerectomies and 1-2 mm central sclerostomies 9.5 mm posterior to the limbus, specifically avoiding vortex veins. Complete resolution of the retinal and choroidal detachments occurred in spite of postoperative ultrasonograms demonstrating residual choroidal-scleral thickening. The effectiveness of this technique in our patient, in light of recent studies demonstrating histochemical and microscopic abnormalities in nanophthalmic sclera, suggests impairment of trans-scleral protein transport as the primary pathophysiologic mechanism in nanophthalmic uveal effusion.


Assessment of autonomic neurodevelopment in the mouse fetuses by using fetal electrocardiography.
Fetal Electrocardiography (FECG) offers unique capabilities for assessment of beat-to-beat fetal heart rate (FHR) and fetal heart rate variability (FHRV), which are indirect markers of autonomic nervous system, its development. In this study the fetal ECG signals, FHR and FHRV are successfully recorded to assess the neurodevelopment in fetal mice in the second and third trimester from days 12.5 to 18.5 by using direct insertion of fetal ECG electrodes in the uterine. FHR increases from day 12.5 till 15.5 reaching a plateau and then shows a sudden increase on the day 18.5. Development of fetal increasing heart rate variability (FHRV) is clearly evident from the results. Short term FHRV (RMSSD) corresponding to parasympathetic nervous system activity and long term FHRV (SDNN) corresponding to sympathetic and parasympathetic nervous system activities increases till day 16.5 and then decreases from day 17.5. The increases in large fluctuations were noticed on days 17.5 and 18.5, which were thought to have caused by uterine contractions before delivery. The ability to assess FHR and FHRV in fetal mice makes a valuable tool for neurodevelopment research in perinatal medicine.


Serotonin catabolism in the central and enteric nervous systems of rats upon induction of serotonin syndrome.
Serotonin, a well-known neurotransmitter in mammals, has been linked to a number of neurological and gastrointestinal disorders. One of these disorders, serotonin syndrome, is a potentially deadly condition caused by increased levels of serotonin in the extracellular space. Information on the neurochemical effects of serotonin syndrome on serotonin catabolism is lacking, particularly in relation to the enteric system of the gastrointestinal tract. Here the catabolism of serotonin is monitored in rats with pharmacologically induced serotonin syndrome, with the catabolites characterized using a specialized capillary electrophoresis system with laser-induced native fluorescence detection. Animals induced with serotonin syndrome demonstrate striking increases in the levels of serotonin and its metabolites. In the brain, levels of serotonin increased 2- to 3-fold in animals induced with serotonin syndrome. A major serotonin metabolite, 5-hydroxyindole acetic acid, increased 10- to 100-fold in experimental animals. Similar results were observed in the gastrointestinal tissues; in the small intestines, serotonin levels increased 4- to 5-fold. Concentrations of 5-hydroxyindole acetic acid increased 32- to 100-fold in the intestinal tissues of experimental animals. Serotonin sulfate showed surprisingly large increases, marking what may be the first time the compound has been reported in rat intestinal tissues.


Ventilatory response to carbon dioxide in humans.
Testing ventilatory responses to CO2 is fraught with difficulties in interpretation and, at present, it can hardly be considered suitable for routine evaluation of patients with pulmonary disease. In spite of the seventy years' work since Haldane's introduction of the CO2 response curve, much remains to be learned about the various components of the regulatory system, and for testing chemosensitivity to CO2 in patients with pulmonary disease, methods more direct than measuring pulmonary ventilation are needed for evaluation of the output of the regulatory system.


Significance of Ebp1 and p53 protein expression in cervical cancer.
In this study, the ErbB3-binding protein (Ebp1) and p53 protein expression in cervical cancer tissues, and its significance in the prognosis of the disease was investigated. Ebp1 and p53 protein expression was detected by immunohistochemical analysis in cervical cancer tissues (N = 60) and normal tissues adjacent to the cancer tissues (N = 60). The rates of positive Ebp1 and p53 protein expression were 35.0 and 60.0%, respectively. Ebp1 and p53 were overexpressed in cervical cancer tissues, compared to normal tissues (P < 0.05). Ebp1 and p53 protein expression was not correlated with age, tumor size, or family tumor history (P > 0.05). However, high levels of expression of Ebp1 and p53 were positively correlated with the TNM stage and lymphatic metastasis in cervical cancer patients (P < 0.05). The combined determination of Ebp1 and p53 expression levels in cervical cancer patients could support the effective prediction of metastatic potential and patient prognosis.


Seropositivity of Chlamydia trachomatis & Toxoplasma gondii among male partners of infertile couples in Odisha, India: A facility-based exploratory study.
Chlamydia trachomatis (CT) is the most common curable sexually transmitted non-viral infection, which can cause urethritis, prostatitis, orchitis and epididymitis among males. Toxoplasma gondii, a protozoan causes toxoplasmosis among humans. These infections may lead to decreased fertility. Hence, this study was aimed to estimate the seropositivity of CT and T. gondii infection among the male partners of infertile couples in Odisha, India. In this facility-based cross-sectional study, first void urine, seminal fluid and blood sample were collected from 153 males attending infertility clinics including 74 healthy controls. Urine and seminal fluid were tested through polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay was used to detect immunoglobulin (Ig) G, IgA and IgM anti-Chlamydia and IgM anti-Toxoplasma antibodies through serum. The prevalence of CT was 1.26 per cent (95% CI: 0.03-6.85) as estimated from semen samples using PCR. We detected anti-Chlamydia antibodies IgM-four per cent [95% confidence interval (CI): 0.83-11.24]; IgA-28.16 per cent (95% CI: 18.13-40.09) and IgG-12.5 per cent (95% CI: 5.87-22.4) among participants. Anti-Toxoplasma antibodies IgM were observed in 27.63 per cent (95% CI: 17.98-39.08) of participants. None of the control samples were found positive. Overall seropositivity of CT and Toxoplasma infections is comparable, which suggests that greater attention is required for screening these infections at clinics, especially among infertile couples.


A Study on Speech Analysis in Acquired Maxillary Defect Patients Treated with Maxillary Obturator.
The aim of the present study was to assess the speech analysis in acquired maxillary defect patients treated with maxillary obturator. Total of 16 patients were considered in the study. The age group of these patients ranged from 40 to 75 years with a mean age of 59.5 years, irrespective of their gender. The surgical obturator was fabricated using self-cure acrylic. The surgical obturator was delivered immediately after surgery. After a healing period of about 2 weeks, the surgical obturator was replaced by an interim prosthesis. This was processed with the help of heat-cure polymethylmethacrylate. The total number of patients was divided into two groups, namely, (A) Definitive obturator group and (B) Interim obturator group. The speech intelligibility (SI), was analyzed. The mean scores for SI before prosthesis in definitive and interim groups were 19.13 ± 3.22 and 19.87 ± 1.72, respectively. This was increased after prosthesis insertion to 24.38 ± 1.30 and 22.37 ± 1.18, which further increased after adaptation period of 2 months to 28.75 ± 1.28 and 24.62 ± 1.59 in two groups. The present study concluded that speech was severely affected by maxillary resection and that rehabilitation with maxillary obturator was successful in restoring these aspects of speech.


Brodalumab: A Review of Safety.
Interleukin (IL)-17 is important in the pathophysiology of psoriasis and has proven to be an effective therapeutic target. Brodalumab, the third commercially available IL-17 antagonist, was approved by the US FDA in February 2017 for the treatment of moderate-tosevere plaque psoriasis. As brodalumab enters the marketplace, it is imperative to investigate its safety profile. We conducted a safety assessment of brodalumab using publically available adverse event data from phase II and III clinical trials. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and candidiasis. The FDA issued a black box warning after six patients treated with brodalumab across four clinical trials committed suicide, but no causal relationship was identified. Current evidence suggests a similar safety profile for brodalumab compared to other IL-17 antagonists used to treat moderate-to-severe plaque psoriasis.


[Research progress of induced pluripotent stem cells in treatment of muscle atrophy].
Muscle atrophy caused by nerve injury is a common and difficult clinical problem. The development of stem cell researches has opened up a new way for the treatment of nerve injury-induced muscle atrophy. The induced pluripotent stem cells(iPSCs)can differentiate into various types of cells and have more advantages than embryonic stem cells (ESCs). After being transplanted into the damaged area, iPSCs are guided by neurogenic signals to the lesion sites, to repair the damaged nerve, promote generation of axon myelination, rebuild neural circuits and restore physiological function. Meanwhile, iPSCs can also differentiate into muscle cells and promote muscle tissue regeneration. Therefore, it would be possible to attenuate muscle atrophy caused by nerve injury with iPSCs treatment.


Intra-abdominal sepsis.
Initially, intra-abdominal contamination with endogenous bacteria produces peritonitis and septicemia. If the infection is localized and the patient survives, the late phase is usually abscess formation. Treatment consists of prompt, thorough surgical drainage, with repair of the diseased or traumatized viscera, as well as the use of preoperative, intraoperative and postoperative antibiotics aimed at both aerobic and anaerobic infecting microflora.


Treating sensitive cervical areas with ozone. A prospective controlled clinical trial.
To determine whether the treatment of hypersensitive teeth with gaseous ozone (Healozone, KaVo 1600 ppm) for 60 seconds reduces pain immediately after treatment and in the longer term. In three private practices in Switzerland, 31 subjects suffering from hypersensitive teeth were treated with gaseous ozone over a period of 54 weeks (one test and one control tooth in each subject). A cross-over design was chosen. The pain level was measured with a Visual Analogue Scale before and after the treatment. The subjects' pain level was reduced by 55% +/- 5.5% immediately after the ozone treatment. Over time, the pain level decreased significantly in all groups: The pain level in the test teeth was significantly reduced in Weeks 0-22 (treatment group, P < 0.001) compared to the pain level before treatment. The pain level in the control group was also reduced significantly over time in Weeks 0-22 (no-treatment, P = 0.025) and in Weeks 22-54 (treatment group, P = 0.0065). Comparing test and control teeth over time, there was no statistically significant difference in pain reduction (P = 0.58).


Rapid measurement method of intracavity phase retardation based on laser frequency splitting.
We present a method for phase retardation measurement of intracavity optical elements which is based on frequency splitting caused by weak phase anisotropy of Nd: YAG. The measurement range covers 0-π and the measurement uncertainty is less than 0.0300 rad. A theoretical analysis is provided to obtain the phase retardation of intracavity optical elements by using the phase difference or frequency difference of two eigenmodes. The minimum error is 0.0036 rad by using the composite wave plate to verify various phase retardation conditions. This work provides a rapid and accurate intracavity method for measuring the phase retardation of optical elements.


Nematic Correlation Length in Iron-Based Superconductors Probed by Inelastic X-Ray Scattering.
Nematicity is ubiquitous in electronic phases of high-T_{c} superconductors, particularly in the Fe-based systems. We used inelastic x-ray scattering to extract the temperature-dependent nematic correlation length ξ from the anomalous softening of acoustic phonon modes in FeSe, underdoped Ba(Fe_{0.97}Co_{0.03})_{2}As_{2}, and optimally doped Ba(Fe_{0.94}Co_{0.06})_{2}As_{2}. In all cases, we find that ξ is well described by a power law (T-T_{0})^{-1/2} extending over a wide temperature range. Combined with the previously reported Curie-Weiss behavior of the nematic susceptibility, these results point to the mean-field character of the nematic transition, which we attribute to a sizable nematoelastic coupling that is likely detrimental to superconductivity.


Use and records of child health handbook focused on growth and development.
Objective To evaluate the use and records of the Child Health Handbook (CHH), especially growth and development. Method Cross-sectional study with 358 mother-child pairs registered in 12 Primary Health Centers (PHCs) of a small municipality. Mothers were interviewed at the PHC from February to April 2013 using a questionnaire. Data analysis was done using WHO Anthro software, Epi InfoTM and Stata. Results Fifty-three percent of the mothers were carrying the CHH at the time of the interview, similar to the proportion of mothers who were instructed to bring the CHH to health appointments. Annotations in the CHH during the visits were reported by 49%. The vaccination schedule was completed in 97% of the CHH, but only 9% and 8% of the CHH, respectively, contained growth charts and properly completed developmental milestones. Conclusion Low rates of use and unsatisfactory record-keeping in the CHH reinforce the need for investment in professional training and community awareness for the CHH to become an effective instrument of promotion of child health.


Inflammatory activation during coronary artery surgery and its dose-dependent modulation by statin/ACE-inhibitor combination.
On-pump coronary artery bypass graft (CABG) surgery triggers an inflammatory response (IR) which may impair revascularization. The study aimed at (1) characterizing the temporal profile of the IR by assaying appropriate markers in both systemic and coronary blood, and (2) determining whether (and which doses of) cardiovascular drugs known to have antiinflammatory properties, namely statins and ACE-inhibitors (ACEI), inhibit the response. Patients scheduled for CABG (n=22) were randomized to statin/ACEI combination treatment at standard doses (STD, ramipril 2.5/simvastatin 20 mg, or atorvastatin 10 mg), or at high doses (HiDo, ramipril 10 mg, or enalapril 20 mg/simvastatin 80 mg, or atorvastatin 40 mg). Plasma levels of interleukin 6, tumor necrosis factor alpha, E-selectin, von Willebrand factor (vWF), and sVCAM-1 were serially assayed (ELISA) before, during, and after CABG. Blood was drawn from an artery, a systemic vein, and the coronary sinus. Myocardial perfusion scans were obtained before and 2 months after surgery in 19 out of 22 subjects. In the STD group both IL-6 and TNF displayed striking increases which were similar at all sites and peaked 10 to 60 minutes after aortic declamping. Such increases were drastically attenuated in the HiDo group. Instead, only modest increases in venous E-selectin, vWF, and sVCAM-1 were observed. Scintigraphic ischemia scores were entirely normalized after versus before CABG in the HiDo but not in the STD treatment group. On-pump CABG surgery is associated with an intense systemic inflammatory response, which can be almost completely prevented by early treatment with high (but not standard) doses of ACE-inhibitors and statins.


Induction of the nuclear orphan receptor RORgamma during adipocyte differentiation of D1 and 3T3-L1 cells.
Here, we analyzed the expression of the three members of the retinoid-like orphan receptor (ROR) nuclear receptor subfamily during adipocyte differentiation. RORalpha and RORgamma mRNA were upregulated during adipocyte differentiation in preadipocyte D1 and 3T3-L1 cells, whereas RORbeta mRNA could not be detected. The induction of RORalpha and RORgamma mRNA succeeded the induction of peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding protein alpha and occurred at a similar time interval as did the increase in aP2 and lipoprotein lipase mRNA. Like the expression of PPARgamma and aP2, the induction of RORgamma mRNA was repressed by tumor necrosis factor alpha and transforming growth factor beta. The induction of adipogenesis by prostaglandin D2 and two thiazolidinediones in the multipotent stem cells C3H10T1/2 was also accompanied by an induction in RORgamma mRNA. In contrast to parental cells, clofibrate induces adipogenesis and RORalpha and RORgamma mRNA in BALB/c3T3 cells that ectopically express PPARgamma. RORgamma mediates its effect on transcription through specific response elements. Cotransfection of RORalpha or RORgamma and (RORgamma response element)4-chloramphenicol acetyltransferase into preadipocyte D1 cells induced transactivation of chloramphenicol acetyltransferase about 100-fold, suggesting that ROR plays a role in the regulation of gene expression in adipocytes. The nuclear orphan receptor Rev-ErbAalpha, which did not exhibit transactivation function, was able to inhibit transactivation by RORgamma at two different levels. Our results show that RORgamma is induced during adipocyte differentiation in D1 and 3T3-L1 cells and functions as an active transcription factor, suggesting a role for RORgamma in the regulation of gene expression during this differentiation process.


Temporal and spectral electrooculographic features in a discrete precision task.
This study aimed to evaluate the utility and applicability of electrooculography (EOG) when studying ocular activity during complex motor behavior. Due to its lower spatial resolution relative to eye tracking (ET), it is unclear whether EOG can provide valid and accurate temporal measurements such as the duration of the Quiet Eye (QE), that is the uninterrupted dwell time on the visual target prior to and during action. However, because of its greater temporal resolution, EOG is better suited for temporal-spectral decomposition, a technique that allows us to distinguish between lower and higher frequency activity as a function of time. Sixteen golfers of varying expertise (novices to experts) putted 60 balls to a 4-m distant target on a flat surface while we recorded EOG, ET, performance accuracy, and putter kinematics. Correlational and discrepancy analyses confirmed that EOG yielded valid and accurate QE measurements, but only when using certain processing parameters. Nested cross-validation indicated that, among a set of ET and EOG temporal and spectral oculomotor features, EOG power was the most useful when predicting performance accuracy through robust regression. Follow-up cross-validation and correlational analyses revealed that more accurate performance was preceded by diminished lower-frequency activity immediately before movement initiation and elevated higher-frequency activity during movement recorded from the horizontal channel. This higher-frequency activity was also found to accompany a smoother movement execution. This study validates EOG algorithms (code provided) for measuring temporal parameters and presents a novel approach to extracting temporal and spectral oculomotor features during complex motor behavior.


Factors affecting functional outcome in patients with intramedullary spinal cord tumors: results from a literature analysis.
Recently, great advances have been made in the surgical treatment of intramedullary spinal cord tumors (IMSCTs). Many articles have been published; but looking at the literature of the last 5 years, there are only descriptive reviews and no works in which a literature statistical analysis was performed. Here, we analyzed the literature to identify potential prognosticators of good functional outcome in IMSCT patients. To level out the selected studies, we stratified patients' neurological status as independent (ambulation possible without caregiver assistance) or disabled (cannot ambulate or can only ambulate with caregiver assistance). 18 out of 125 articles were included in the analysis (691 patients). A significant higher percentage of gross total resection (GTR) in ependymomas, hemangioblastomas and cavernomas compared to the astrocytomas (particularly high-grade gliomas) was observed. We found a strong correlation between a good pre-operative neurological function and a good post-operative and at follow-up (FU) neurological status and between GTR and a good post-operative and at FU neurological status. A significant better outcome was found in ependymomas, hemangioblastomas and cavernomas compared to astrocytomas. Our analysis suggests that an early surgery could be reasonable in IMSCTs, because a good pre-operative neurological function is a strong predictor of good neurological outcome. In patients with high-grade gliomas, there is no indication to attempt a GTR due to the infiltrative growth pattern of this tumor that leads to a higher surgical morbidity. Although not innovative, the evidences of our literature statistical analysis strengthen the results from previous surgical series and descriptive reviews.