Lightweight and Efficient Image Dehazing Network Guided by Transmission Estimation from Real-World Hazy Scenes.
In this paper, a transmission-guided lightweight neural network called TGL-Net is proposed for efficient image dehazing. Unlike most current dehazing methods that produce simulated transmission maps from depth data and haze-free images, in the proposed work, guided transmission maps are computed automatically using a filter-refined dark-channel-prior (F-DCP) method from real-world hazy images as a regularizer, which facilitates network training not only on synthetic data, but also on natural images. A double-error loss function that combines the errors of a transmission map with the errors of a dehazed image is used to guide network training. The method provides a feasible solution for introducing priors obtained from traditional non-learning-based image processing techniques as a guide for training deep neural networks. Extensive experimental results demonstrate that, in terms of several reference and non-reference evaluation criteria for real-world images, the proposed method can achieve state-of-the-art performance with a much smaller network size and with significant improvements in efficiency resulting from the training guidance.


Plasma cytokine levels in a population-based study: relation to age and ethnicity.
Aging is one factor believed to contribute to processes that underlie chronic low-grade inflammation in older adults. Moreover, more recent studies have suggested that cytokine levels are influenced by ethnicity. In this study, we determined plasma cytokine profiles in a population-based sample (n = 1,411; aged 25-91 years) to determine the relationship between circulating cytokine levels, aging, and ethnicity. We measured interleukin-1 receptor antagonist (IL-1ra), interleukin (IL)-6, -10, C-reactive protein (CRP), and tumor necrosis factor-receptor 1 (TNF-r1). IL-6 and TNF-r1 significantly increased with age, whereas IL-1ra, IL-10, and CRP did not significantly increase with age. After adjusting for age, non-Hispanic whites had significantly higher levels of IL-1ra than Mexican Americans, whereas non-Hispanic blacks had significantly higher levels of IL-6 and CRP than Mexican Americans as well as non-Hispanic whites. CRP levels in non-Hispanic blacks were no longer significantly higher after adjusting for body mass index (BMI), indicating that BMI is an important predictor of this inflammatory marker. These results demonstrate that cytokine levels are influenced by both age and ethnicity. Furthermore, these results show that inflammatory profiles for Mexican Americans are lower than non-Hispanic whites and non-Hispanic blacks.


Bone scan in enthesopathy involving tendo Achilles.
Inflammatory enthesitis is a hallmark of spondyloarthropathies (SSA) and may antedate other clinical manifestations. The involvement of Achilles tendon and plantar aponeurosis is common, with strong tendency toward fibrosis and calcification. We are describing imaging characteristics in a patient with positive HLA B-27 antigen with bilateral calcific achilles tendonitis who had pain in heels for 3 years.


Dechlorination of chloroethylenes by cob(I)alamin and cobalamin model complexes.
Cobalt-mediated dehalogenation reactions, specifically those that employ cobalamin, have attracted particular attention because these complexes rapidly degrade tetrachloroethylene (PCE) and trichloroethylene (TCE), which are common groundwater contaminants. Although questions remain about the relative importance of several pathways, both radicals and organometallic intermediates, specifically chlorovinyl complexes, play an important role in these processes. This Perspective highlights recent studies focused on elucidating the mechanism of chloroethylene degradation, including experimental studies on PCE and TCE dechlorination, computational studies, preparation of model complexes, and the study of model catalytic systems.


Surface wave velocity measurement using reflections from laser scribed grooves.
The measurement of ultrasonic surface wave (USW) velocity is difficult using the pulse overlap method (POM) in the presence of an externally applied stress. Coupling variations between the sample and the transducer cause nonuniform distortions of the two received pulses which makes the overlap condition difficult to determine over an extended stress range. The adaptation in this paper of a single transducer configuration to generate and detect the USW eliminates coupling variations between two or more transducers. In addition, two parallel, precisely positioned and contoured grooves are laser scribed on the sample surface to provide the necessary overlap echoes. Since both echoes are reflected only once by identical grooves and are equally affected by the distortions due to coupling variations, the overlap condition is relatively unaffected by the external stress and the accuracy of the USW velocity measurement is increased significantly.


Choice enhances performance in non-insulin dependent diabetics and controls.
Cognitive performance on a number of tasks is poorer in individuals with non-insulin dependent diabetes mellitus (NIDDM) than in age-matched nondiabetics. In this study, diabetic and nondiabetic individuals, 55-74 years of age, learned target words, half of which were self-chosen and the remainder assigned. To evaluate susceptibility to background interference, each target was accompanied by one or more unrelated background words. On a recognition test, susceptibility to background interference appeared to be greater in diabetic individuals. The allocation of processing resources to target and background stimuli was more uniform in diabetic than in nondiabetic individuals. While choice improved recognition of target and background words for both groups, its effectiveness was attenuated in NIDDM. Choice facilitates the differentiation of target from background stimuli--a process that may reduce interference from background stimuli.


Conformational analysis of protein and nucleic acid fragments with the new grid search algorithm FOUND.
The new computer algorithm FOUND, which is implemented as an integrated module of the DYANA structure calculation program, is capable of performing systematic local conformation analyses by exhaustive grid searches for arbitrary contiguous fragments of proteins and nucleic acids. It uses torsion angles as the only degrees of freedom to identify all conformations that fulfill the steric and NMR-derived conformational restraints within a contiguous molecular fragment, as defined either by limits on the maximal restraint violations or by the fragment-based DYANA target function value. Sets of mutually dependent torsion angles, for example in ribose rings, are treated as a single degree of freedom. The results of the local conformation analysis include allowed torsion angle ranges and stereospecific assignments for diastereotopic substituents, which are then included in the input of a subsequent structure calculation. FOUND can be used for grid searches comprising up to 13 torsion angles, such as the backbone of a complete alpha-helical turn or dinucleotide fragments in nucleic acids, and yields a significantly higher number of stereospecific assignments than the precursor grid search algorithm HABAS.


GPR34 in spinal microglia exacerbates neuropathic pain in mice.
Neuropathic pain is caused by sensory nerve injury, but effective treatments are currently lacking. Microglia are activated in the spinal dorsal horn after sensory nerve injury and contribute to neuropathic pain. Accordingly, molecules expressed by these cells are considered potential targets for therapeutic strategies. Our previous gene screening study using a mouse model of motor nerve injury showed that the G-protein-coupled receptor 34 gene (GPR34) is induced by nerve injury. Because GPR34 is now considered a microglia-enriched gene, we explored the possibility that it might be involved in microglial activation in the dorsal horn in a mouse model of neuropathic pain. mRNA expression of GPR34 and pro-inflammatory molecules was determined by quantitative real-time PCR in wild-type and GPR34-deficient mice with L4 spinal nerve injury. In situ hybridization was used to identify GPR34 expression in microglia, and immunohistochemistry with the microglial marker Iba1 was performed to examine microglial numbers and morphology. Mechanical sensitivity was evaluated by the von Frey hair test. Liquid chromatography-tandem mass spectrometry quantified expression of the ligand for GPR34, lysophosphatidylserine (LysoPS), in the dorsal horn, and a GPR34 antagonist was intrathecally administrated to examine the effect of inhibiting LysoPS-GPR34 signaling on mechanical sensitivity. GPR34 was predominantly expressed by microglia in the dorsal horn after L4 nerve injury. There were no histological differences in microglial numbers or morphology between WT and GPR34-deficient mice. However, nerve injury-induced pro-inflammatory cytokine expression levels in microglia and pain behaviors were significantly attenuated in GPR34-deficient mice. Furthermore, the intrathecal administration of the GPR34 antagonist reduced neuropathic pain. Inhibition of GPR34-mediated signal by GPR34 gene deletion reduced nerve injury-induced neuropathic pain by suppressing pro-inflammatory responses of microglia without affecting their morphology. Therefore, the suppression of GPR34 activity may have therapeutic potential for alleviating neuropathic pain.


Uptake and Growth-promoting Activity of Indoleacetic Acid in Segments of Cold-hardened Wheat Coleoptiles.
Seedings of winter wheat (Triticum aestivum L. cv. Kharkov MC 22) were grown at 24 C (unhardened) and 4 C (hardened). Indoleacetic acid (IAA) was added to excised coleoptile segments after lengthy incubation and their responses were determined by photometric auxanometry at both 25 C and 5 C. The segments' rates of uptake of (14)CIAA were also compared at both temperatures. Cold hardening had no significant effect on the rates of elongation and uptake in a saturating concentration of IAA (2 to 10 muM) at either temperature. Elongation was more sensitive to temperature of measurement than was uptake. At suboptimal concentrations of IAA and 25 C, hardened coleoptiles took up [2-(14)C]-IAA twice as fast but elongated half as fast as unhardened coleoptiles. This and the lack of effect of cold hardening on apparent uptake of [1-(14)C]-IAA raised the possibility that a higher rate of IAA-decarboxylation was coupled with the higher rate of uptake of IAA by hardened coleoptiles. Homeostatic hormonal regulation was also evident in the same endogenous rates of elongation of segments of cold-hardened and unhardened coleoptiles.


Reconstruction of the severely resorbed maxilla with dental implants in the augmented maxillary sinus: a 5-year clinical investigation.
The aim of this investigation was to determine the long-term clinical outcome and predictability of the maxillary sinus augmentation procedure utilizing a variety of bone augmentation materials. The augmentation materials evaluated were a xenograft alone (Bio-Oss), an alloplast alone (Interpore), a xenograft-alloplast combination (Bio-Oss mixed with Interpore in a 1:1 ratio), an alloplast (Interpore) mixed with autogenous bone from the iliac crest (in a 1:3 ratio), and an alloplast (Interpore) mixed with autogenous bone from the chin (in a 1:1 ratio). A total of 340 plasma-sprayed cylinder implants (IMZ) were placed, either simultaneously with the sinus augmentation procedure (235 implants), or 6 months after the procedure (105 implants) in 133 patients with insufficient bone volume in the posterior maxilla. The implants were restored with a total of 151 fixed detachable ceramometal prostheses and evaluated up to a 5-year period. Clinical evaluations included yearly assessments of peri-implant inflammation, implant mobility, and clinical attachment levels. Radiographs were also taken prior to sinus augmentation surgery, at abutment connection, at completion of the restoration, and thereafter at yearly intervals. All of the implants placed into the augmented sinuses achieved osseointegration. Only four implants (1.2%) failed to maintain osseointegration after prosthesis placement, yielding an implant survival rate of 98.8% during the entire course of the study. Of the 340 implants, 307 (90.3%) were considered successful according to the success criteria used. Gender, implant length and location, remaining bone height, and type of bone augmentation material had no effect on implant success. None of the 151 prostheses was lost during the observation period. The results of this study support the long-term clinical predictability of maxillary sinus augmentation procedures for the rehabilitation of the edentulous posterior maxilla with implant-supported prostheses.


Long non-coding RNA Dlx6os1 serves as a potential treatment target for diabetic nephropathy via regulation of apoptosis and inflammation.
The present study investigated the effect of long non-coding RNA (lncRNA) Dlx6os1 silencing on cell proliferation, apoptosis and fibrosis, and further explored its influence on the mRNA expression profile in mouse mesangial cells (MMCs) of a diabetic nephropathy (DN) cellular model. A DN cellular model was constructed in SV40 MES13 MMCs under high glucose conditions (30 mmol/l glucose culture). lncRNA Dlx6os1 short hairpin (sh)RNA plasmids and negative control (NC) shRNA plasmids were transfected into the MMCs of the DN cellular model as the sh-lncRNA group and sh-NC group respectively. The mRNA expression profile was determined in the sh-lncRNA and sh-NC groups. Compared with the sh-NC group, the cell proliferation, mRNA and protein expression levels of proliferative markers (cyclin D1 and proliferating cell nuclear antigen) as well as fibrosis markers (fibronectin and collagen I) were suppressed, whereas cell apoptosis was promoted in the sh-lncRNA group. The mRNA expression profile identified 423 upregulated mRNAs and 438 downregulated mRNAs in the sh-lncRNA group compared with the sh-NC group. Additionally, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the differentially expressed mRNAs were enriched in apoptosis and inflammation-related pathways. Further gene-set enrichment analysis of apoptosis and inflammation revealed that lncRNA Dlx6os1 inhibition promoted apoptosis and suppressed inflammation in MMCs of the DN cellular model. In conclusion, lncRNA Dlx6os1 may serve as a potential treatment target for DN via regulation of multiple apoptosis- and inflammation-related pathways.


Enterovirus D68 Causing Acute Respiratory Infection: Clinical Characteristics and Differences With Acute Respiratory Infections Associated With Enterovirus Non-D68.
Enterovirus (EV) D68 is mainly associated with acute respiratory infection (ARI). Since 2014, when outbreaks in different countries were observed, this emerging virus was considered a potential threat to public health. During 2015-2017, the presence of enterovirus RNA was investigated in all respiratory samples of children younger than 15 years of age with ARI, obtained for virologic studies in the Pediatric Emergency Care Units and wards of 2 hospitals in Gipuzkoa (Spain), using a commercial multiplex real-time polymerase chain reaction. When enterovirus was detected, a polymerase chain reaction to amplify a specific viral polyprotein (VP1) gene region of EV-D68 was performed. In 2016, EV-D68 circulation was associated to ARI, with the highest incidence in the spring months. EV-D68 was detected in 44 children, mean age 30.1 ± 31.7 months old, 23 (52.3%) of them females and 17 (38.6%) with underlying respiratory medical conditions. Thirty-two patients (72%) required hospital admission, receiving the discharge diagnosis of recurrent wheezing (37.5%), asthmatic crisis (37.5%) or bronchiolitis (12.5%). Seven children (15.9%) needed the support of the pediatric intensive care unit. When coinfections were excluded, children with EV-D68 infection presented with increased work of breathing, recurrent wheezing or asthmatic crisis, more frequently than those with ARI associated with EV non-D68. Moreover, clinical outcomes (hospitalization, respiratory support) were more severe. All 44 EV-D68 strains detected belonged to lineage B3. EV-D68 circulated widely in Gipuzkoa during 2016 and was associated with severe ARI. In children with severe ARI of unknown etiology, the presence of EV-D68 should be considered.


Design principles and common pool resource management: an institutional approach to evaluating community management in semi-arid Tanzania.
This paper analyses the role of institutions in the management of common pool resources (CPRs) in semi-arid Tanzania. Common property regimes have often been considered inadequate for the management of CPRs because of the problems of excludability, but they are becoming more widely supported as the way forward to overcome the problems of resource use and degradation in developing countries. A series of design principles for long enduring common property institutions have been proposed by Ostrom, but there is concern that they are not applicable to a wide range of real life situations or that they may be specific to certain types of CPR. Here, we compare these principles to the situation prevailing in 12 villages in six districts in semi-arid Tanzania. Data on management institutions were collected through semi-structured interviews and meetings at district and village level. The combined information was used to make a qualitative assessment of the strength with which each design principle appeared to operate in the management of forest, pasture and water resources. Boundaries, conflict and negotiation in CPR management are of key importance in semi-arid regions. However, the need for flexibility in order to deal with ecological uncertainty means that many management institutions would be considered weak or absent according to the design principle approach. This supports the view that the design principles should not be used as a 'blueprint to be imposed on resource management regimes' rather that they provide a framework for investigating common property regimes with the proviso that, certainly for semi-arid regions, they may highlight where management cannot be explained by institutional theory alone.


Genetic selection modulates feeding behavior of group-housed pigs exposed to daily cyclic high ambient temperatures.
This study was conducted to evaluate the effect of genetic selection (Lines A and B; Line A pigs have a greater proportion of Pietrain genes than those from Line B and therefore, selected for improved lean tissue accretion) on the feeding behavior of group-housed pigs exposed to daily cyclic high ambient temperatures. Feeding behavior of 78 barrows housed together in a single room was recorded in real time by five automatic feeders. The feeders registered each visit of each pig (day, hour, min, and second) and the amount of feed requested. Daily cyclic high ambient temperature was induced exposing pigs at 22°C from 18.00 to 10.00 h and 30°C from 10.01 to 17.59 h. From this temperature variation, day-period was divided into: 22°C(06-10h), from 6.00 to 10.00 h; 30°C(10-18h), from 10.01 to 17.59 h; and 22°C(18-06h), from 18.00 to 5.59 h. Meal criteria was estimated based on the probability of animals starting a new feeding event within the next minute since the last visit (Pstart). After defining the meal criteria, the number of meals (n), feed intake rate (g/min), feed intake (g/meal), feeder occupancy (min/meal), and interval between meals (min) of each animal were calculated. Greatest probability of starting to feed was observed at 22°C(06-10h), followed by 30°C(10-18h) and then 22°C(18-06h). Regardless of time period, pigs from line A had greater feed intake rate and lower feed intake, feed occupancy per meal and probability of starting a meal when compared with line B pigs. Only line A pigs had greater feed intake and feeder occupancy per meal at 22°C(18-06h) than remainder of the day. This indicates that pig feeding pattern is strongly related to the circadian rhythm. However, the genetic selection for improved lean tissue accretion may modulate pigs feeding behavior under daily cyclic high ambient temperatures.


Endobronchial ultrasound for tubercular mediastinal adenopathy and its comparison with traditional tools.
SETTING: Endobronchial ultrasound (EBUS) is now the preferred tool to sample malignant mediastinal lesions. Data on its role in tubercular mediastinal adenopathy are limited.OBJECTIVE: To evaluate the efficacy of EBUS in diagnosing tubercular mediastinal lymphadenopathy and correlate the cytological and microbiological results obtained on aspirate with standard methods (radiology and the tuberculin skin test) suggesting tuberculosis (TB).DESIGN: A prospective study of 125 patients with suspected tubercular mediastinal lymphadenopathy who underwent EBUS-transbronchial needle aspiration. Only patients with a microbiologically confirmed diagnosis or unequivocal clinico-radiological response to anti-TB treatment during follow-up were included.RESULTS: A total of 122 patients showed findings suggesting TB on cytopathology (sensitivity 97.6%), 105 (84%) of whom had microbiological evidence of TB (positive smear/culture or both). Performing staining for acid-fast bacilli on slides prepared during the procedure vs. only on samples submitted in saline significantly improved the yield. Only 92 patients (73.6%) were Mantoux-positive. Cytology was more sensitive than computed tomography in picking up necrosis. Granulomas, with or without necrosis, were equally likely to be microbiologically positive. However, presence of only necrosis in a TB-endemic region invariably points towards TB diagnosis.CONCLUSIONS: EBUS was highly sensitive and specific for diagnosis of mediastinal TB and may be considered the investigation of choice for tubercular mediastinal adenopathy.


Laparoscopy in the early diagnosis and management of sclerosing encapsulating peritonitis.
Sclerosing encapsulating peritonitis (SEP) is a rare and dreaded complication that can occur in patients undergoing peritoneal dialysis (PD). Although risk factors have been identified, the diagnosis is difficult and is usually made late in the disease after extensive fibrosis of the peritoneal membrane has occurred, at which point therapy is often fruitless. The high mortality rate of SEP is due to complications resulting from recurrent bowel obstruction, malnutrition, and sepsis. We report three patients with signs and symptoms suggestive of SEP all of whom had normal abdominal CT scans. Nevertheless, each patient underwent diagnostic laparoscopy, which confirmed the clinical suspicion of SEP. In each case, the diagnosis was made before extensive peritoneal fibrosis had occurred allowing therapeutic intervention at an early stage. All three patients subsequently became asymptomatic and thrived. This clinical improvement was supported by the lack of progression to overt peritoneal fibrosis on repeat laparoscopy. We conclude that a high index of suspicion in conjunction with a low threshold for diagnostic laparoscopy may be an effective strategy to establish an early diagnosis and treatment regimen for SEP. Additionally, repeat laparoscopy can be used to guide the length of therapy. These interventions may ultimately improve the long-term morbidity and mortality of SEP.


Correction for hidden confounders in the genetic analysis of gene expression.
Understanding the genetic underpinnings of disease is important for screening, treatment, drug development, and basic biological insight. One way of getting at such an understanding is to find out which parts of our DNA, such as single-nucleotide polymorphisms, affect particular intermediary processes such as gene expression. Naively, such associations can be identified using a simple statistical test on all paired combinations of genetic variants and gene transcripts. However, a wide variety of confounders lie hidden in the data, leading to both spurious associations and missed associations if not properly addressed. We present a statistical model that jointly corrects for two particular kinds of hidden structure--population structure (e.g., race, family-relatedness), and microarray expression artifacts (e.g., batch effects), when these confounders are unknown. Applying our method to both real and synthetic, human and mouse data, we demonstrate the need for such a joint correction of confounders, and also the disadvantages of other possible approaches based on those in the current literature. In particular, we show that our class of models has maximum power to detect eQTL on synthetic data, and has the best performance on a bronze standard applied to real data. Lastly, our software and the associations we found with it are available at http://www.microsoft.com/science.


Efficient in vitro transcription of plant nuclear tRNA(Ser) genes in a nuclear extract from tobacco cultured cells.
A nuclear extract derived from tobacco cultured BY-2 cells supports RNA polymerase III-dependent transcription of Arabidopsis tRNA(Ser) genes. Primer extension analysis indicated that the transcription starts at 6 bp upstream from the 5' end of tRNA coding region. Procedures for nuclear extraction and in vitro reaction conditions have been optimized for tRNA transcription, which allows direct detection of de novo synthesized tRNA by gel electrophoresis. This improved in vitro system yields a mature-sized tRNA of 85 nucleotides from the Arabidopsis tRNA(Ser) gene, indicating that efficient processing of the pre-tRNA also occurs in the tobacco nuclear extract.


Chinese Clinical Trial Registry: mission, responsibility and operation.
As a national public clinical trial registry and a recognized Primary Registry of the WHO ICTRP, the Chinese Clinical Trial Registry (ChiCTR) has responsibility to disseminate knowledge about clinical trial transparency, which is an important ethical issue for healthcare studies involving humans, and to promote the quality of healthcare studies in China. This article describes the mission, policy and operation of the ChiCTR. We discuss the need to improve the quality of clinical trials and our ideas for new developments. The registration of clinical trials is an ethical responsibility and obligation for researchers. A clinical study is a public event itself, which needs the participation of the public, and its results should also be seen as a service to the public. Therefore, the public have the right to know how a study is progressing.


A simple method for environmental cell depressurization for use with an electron microscope.
With the aid of the environmental cell (EC) in electron microscopy, hydrated specimens have been observed at high resolutions that optical microscopy cannot attain. Due to the ultra-high vacuum conditions of the inner column of the electron microscope, the EC requires sealing films that are sufficiently thin to allow electron transmission and that are sufficiently tough to withstand the pressure difference between the inside and outside of the EC. However, most hydrated specimens can be observed at low vacuum because the saturated vapor pressure of water is known to be 0.02 atm at room temperature. These concepts have been used in the differential pumping system, but it is complicated and relatively expensive. In this work, we propose a simple method for depressurization of the EC using a 'balloon structure' and demonstrate the theoretical benefits and practical improvement for specimen observations in low-vacuum conditions.


Coordination polymers: what has been achieved in going from innocent 4,4'-bipyridine to bis-pyridyl ligands having a non-innocent backbone?
The last two decades have witnessed the research activities in the area of coordination polymers (CPs), which are structurally diverse and functionally intriguing materials. In this endeavor, the most exploited ligand has been a structurally rigid N-donor compound having an innocent backbone (incapable of forming hydrogen bond) namely 4,4'-bipyridine. Much has been achieved by exploiting this wonder ligand in the area of CPs. However, the positional isomers such as 3,3'-bipyridine or 4,3'-bipyridine (which understandably induce diverse ligating topology as compared to their more symmetrical 4,4' counterpart) were not exploited in much detail presumably because of the difficulty in their synthetic accessibility. To get access to such N-donor ditopic ligands having diverse ligating topology, much efforts have been focused in the last decade or so to design such positional isomers of 4,4'-bipyridine having a non-innocent backbone (capable of forming hydrogen bond). The principal focus of such studies is to decipher the effect of diverse ligating topology and the non-innocent backbone of the ligands on the overall supramolecular structures and functions of the resultant CPs. This tutorial review aims at highlighting some of the developments of such structurally diverse and functionally intriguing CPs derived from N-donor ditopic ligands having a non-innocent backbone.


High incidence of molecular defects of the CYP21 gene in patients with premature adrenarche.
On the basis of hormonal studies, the incidence of defective steroidogenesis in children with premature adrenarche (PA) in the various reports ranges from 0-54%. Molecular studies have not been reported to date. The aim of the present study was to search for defects in the CYP21 gene in children with PA and to detect possible correlations of the molecular defect to pertinent hormonal and clinical data. In 48 children with PA (40 females and 8 males) and without signs of virilization, a Synachten test and molecular studies were carried out. DNA analysis was performed using the Southern blot technique and allele-specific PCR. Synachten (0.25 mg) was given i.v., and 17-hydroxyprogesterone and cortisol were determined at 0 and 60 min. At baseline, delta4-androstenedione, dehydroepiandrosterone sulfate, and 11-deoxycortisol were also determined. Bone age was evaluated using the Greulich and Pyle atlas. Abnormal genotype was detected in 45.8% of the studied subjects; 8.3% were homozygotes, with genotypes concordant with the nonclassical phenotype of 21 hydroxylase deficiency, and 37.5% were heterozygotes for 9 different molecular defects of the CYP21 gene. The children with no detectable molecular defect were designated normal. The 60 min post-Synachten values in homozygotes (17.9 +/- 7.1 ng/mL) and heterozygotes (7.1 +/- 3.6 ng/mL) were significantly higher than that in normal subjects (3.3 +/- 1.5 ng/mL), but with significant overlapping of values. The mean difference between bone age and chronological age differed in the three groups with overlapping values. The basal delta4-androstenedione level was lower in the normal subjects (0.65 +/- 0.3 ng/mL) than in those with abnormal genotype (1.1 +/- 0.8 ng/mL). The data indicate that the incidence of molecular defects in PA is quite high. The CYP21 heterozygocity is clinically expressed in some subjects prepubertally. In a significant number of cases the genotype cannot be predicted by the age of onset of PA, the mean difference between bone age and chronological age, or the results of a Synachten test. Follow-up of these children through puberty is imperative and may reveal the clinical significance of the molecular defect, namely more hypertrichosis, intense acne, early puberty, possible abnormal menses, and/or fertility problems in the affected.


Examining Normative Reference Values and Item-Level Symptom Endorsement for the Quality of Life in Neurological Disorders (Neuro-QoL™) v2.0 Cognitive Function-Short Form.
We examined the normative reference values, item-level symptom endorsement, internal consistency reliability, and the base rates of symptoms endorsed for the quality of life in neurological disorders (Neuro-QoL™) v2.0 Cognitive Function-Short Form. The Neuro-QoL™ v2.0 Cognitive Function-Short Form measures subjective cognitive difficulties. The normative sample from the U.S. general population was stratified by gender, education, health status, self-reported diagnosis of depression or anxiety, and recent mental health symptoms (i.e., endorsed frequent anxiety or depression symptoms in the last week). A cohort of 1,009 adults completed this scale and their mean score was 32.60 (SD = 6.89). The base rates of those who reported zero cognitive symptoms were consistently higher among the healthy samples (healthy men = 79.2%; all men = 63.9%; healthy women = 90.2%; all women = 80.0%). Endorsing three or more cognitive symptoms was more common in the mental health subgroups for both men (full men's sample [n = 493] = 17.6%; depression subgroup [n = 70] = 30.0%; anxiety subgroup [n = 61] = 29.5%; mental subhealth group [n = 70] = 38.6%) and women (full women's sample [n = 516] = 7.4%; depression subgroup [n = 123] = 13.0%; anxiety subgroup [n = 103] = 12.6%; mental health subgroup [n = 101] = 14.9%). Internal consistency was measured using Cronbach's α and ranged from 0.87 to 0.94 across groups. The Neuro-QoL™ v2.0 Cognitive Function-Short Form is a brief, efficient, and reliable measure of perceived cognitive difficulties. As expected, individuals with a favorable overall health and quality of life reported less cognitive symptoms than the total sample, whereas individuals with mental health difficulties reported more. These normative values and base rates stratified by gender, overall health, and mental health status may be useful when interpreting this measure in clinical practice.


Investigation of microbial elicitation of trans-resveratrol and trans-piceatannol in peanut callus led to the application of chitin as a potential elicitor.
It is well-known that the invasion of microbes such as fungi in some plants, including peanut, can induce the biosynthesis of stilbenoids such as trans-resveratrol and trans-piceatannol. However, in a recent study it was found that not all kinds of microorganisms possessed such potential. The Gram-negative bacterium Pseudochrobactrum asaccharolyticum isolated from the peanut callus failed to act as an elicitor. After systematic investigation, the different inductive effects between fungi and Gram-negative bacteria were attributed to the chitin content of the cell wall. Results showed significantly more trans-resveratrol and trans-piceatannol was induced by fungi (8.92-16.35 and 2.15-7.01 microg/g of fresh calluses, respectively) than by bacteria (1.77-2.72 and 0.16-0.52 microg/g of fresh calluses, respectively), regardless of species and viability. Such great differences prompted the direct utilization of chitin, the distinctive component of fungal cell wall, as an elicitor. The results that trans-resveratrol induced by chitin was about two-thirds the amount induced by sterilized fungi, whereas trans-piceatannol (2.55+/-0.60 microg/g) was close to that by sterilized fungi, revealed chitin is not only an important fungal constituent responsible for the induction of trans-resveratrol and trans-piceatannol but also an efficient elicitor by itself. These findings suggested sterilized fungi and chitin can be used as a safe and fast elicitor, as far as the risk of viable microbes is concerned, to induce trans-resveratrol and trans-piceatannol in the well-controlled peanut tissue culture.


Evaluation of the Impacts of Formulation Parameters on the Pharmacokinetics and Bioequivalence of Risperidone Orodispersible Film: a Physiologically Based Pharmacokinetic Modeling Approach.
The purpose of this study was to investigate the impacts of the formulation parameters on the pharmacokinetics and bioequivalence of risperidone orodispersible film (ODF) using physiologically based pharmacokinetic model. The pharmacokinetic profiles of two risperidone ODFs, which exhibit different in vitro dissolution, were examined in Beagle dogs after supralingual administration. Subsequently, a physiologically based pharmacokinetic (PBPK) model was constructed to evaluate the in vivo performance of risperidone ODF. The parameter sensitivity analysis (PSA) was used to access the impacts of formulation parameters on the pharmacokinetics of risperidone. Moreover, the validated PBPK model was applied to predict human pharmacokinetic profiles and examine the bioequivalence of these two ODFs. These two ODFs displayed similar risperidone pharmacokinetic profiles in dogs. The parameter sensitivity analysis indicated that the changes in the solubility, particle size, particle density, and diffusion coefficient did not have obvious influence on the in vivo properties of risperidone ODF. Alternation of the in vitro complete dissolution time in water from 15 to 30 min led to a 30% decrease in Cmax and 20% of increase in Tmax. AUC0-∞ would be decreased if risperidone was not fully released within 1 h. As both ODFs completely released risperidone within 15 min, the difference in the extent of in vivo absorption, intestinal regional absorption location, and plasma concentration-time curves between these two ODFs was almost negligible. Consequently, a bioequivalence was foreseen in humans. The in vitro cumulative dissolution percentage in water at 15 min was found to be the major determinant on the in vivo properties of risperidone ODF. PBPK modeling appears to be an innovative strategy to guide the development of risperidone ODF.


[A bupivacaine-morphine combination by intrathecal route: correlation between pain relief and postoperative neuroendocrine response].
The purpose of the present study was to assess the repercussion of morphine injected in the intrathecal space on postoperative neuroendocrine response and the correlation with pain relief in the postop period. We studied 50 healthy patients (ASA I-II) submitted to orthopaedic surgery under general anaesthesia (N = 25) or spinal anaesthesia (N = 25). In the group under general anaesthesia we observed a hypersecretion of ADH, ACTH, cortisol and aldosterone during and after surgery. In the group un spinal anaesthesia, it was evident, on the contrary, a blockade of the neuroendocrine response during surgery, as well as an attenuation during postoperative period. Intraoperative and postoperative bleeding with spinal anaesthesia was significantly lower (p less than 0.01; p less than 0.05 respectively) than with general anaesthesia. Postoperative analgesia was excellent in group with spinal anaesthesia; the average duration of analgesia was 16.3 hours. We conclude that small intrathecal doses of morphine have beneficial effects and may be used usefulness in orthopaedic surgery.


[Cereal related complaints in children].
There's a lot of attention for gluten-free diets on social media. Doctors get many questions about gluten sensitivity or possible wheat allergy. With some basic knowledge, it's easier to give answers to these questions and to prevent unnecessary and sometimes harmful diets. This article gives basic information about cereals, gluten, grasses and their crossreactivity. We give an overview about the differences between celiac disease, gluten sensitivity and IgE-mediated wheat allergy. We also describe diagnostics, treatment and natural history of coeliakie, gluten sensitivity and wheat or cereal allergy.


Modeling of Miniemulsion Polymerization of Styrene with Macro-RAFT Agents to Theoretically Compare Slow Fragmentation, Ideal Exchange and Cross-Termination Cases.
A 5-dimensional Smith-Ewart based model is developed to understand differences for reversible addition-fragmentation chain transfer (RAFT) miniemulsion polymerization with theoretical agents mimicking cases of slow fragmentation, cross-termination, and ideal exchange while accounting for chain length and monomer conversion dependencies due to diffusional limitations. The focus is on styrene as a monomer, a water soluble initiator, and a macro-RAFT agent to avoid exit/entry of the RAFT leaving group radical. It is shown that with a too low RAFT fragmentation rate coefficient it is generally not afforded to consider zero-one kinetics (for the related intermediate radical type) and that with significant RAFT cross-termination the dead polymer product is dominantly originating from the RAFT intermediate radical. To allow the identification of the nature of the RAFT retardation it is recommended to experimentally investigate in the future the impact of the average particle size (dp) on both the monomer conversion profile and the average polymer properties for a sufficiently broad dp range, ideally including the bulk limit. With decreasing particle size both a slow RAFT fragmentation and a fast RAFT cross-termination result in a stronger segregation and thus rate acceleration. The particle size dependency is different, allowing further differentiation based on the variation of the dispersity and end-group functionality. Significant RAFT cross-termination is specifically associated with a strong dispersity increase at higher average particle sizes. Only with an ideal exchange it is afforded in the modeling to avoid the explicit calculation of the RAFT intermediate concentration evolution.


Structural and functional changes in the canine shoulder after cessation of immobilization.
The functional and structural consequences of remobilization of the glenohumeral joint after 12 weeks of immobilization were studied in 10 beagle dogs. The dogs were grouped in pairs: 2 were used as controls, and in 8 others 1 forelimb was immobilized. At the end of 12 weeks, 2 dogs in the experimental group were euthanized, as were the 2 dogs used as controls. The cast was removed from the other 6 dogs, and the remobilized animals were euthanized in pairs at the end of 4, 8, and 12 weeks. It was found that after 12 weeks of immobilization, the passive range of motion was markedly impaired, intraarticular pressure was raised during movements, and the filling volume of the joint cavity was reduced. Histologically, the capsule showed synovial lining hyperplasia and vascular proliferation in the wall. Immunohistochemical labeling for collagen Types I and III failed to show an increase of fibrous collagens in the capsular wall. Both the functional and structural changes were unaltered after 4 weeks of remobilization, but after 8 weeks they began to reverse, and they returned to normal levels after 12 weeks. Both functional and structural changes after 12 weeks of immobilization of the uninjured glenohumeral joint are reversible by remobilization. The collagen composition of the capsule seems unrelated to the degree of capsular contraction that occurs during 12 weeks of immobilization and subsequent remobilization.


A DATA-DRIVEN APPROACH TO PRIOR EXTRACTION FOR SEGMENTATION OF LEFT VENTRICLE IN CARDIAC MR IMAGES.
In this paper, we propose a data-driven approach that extracts prior information for segmentation of the left ventricle in cardiac MR images of transplanted rat hearts. In our approach, probabilistic priors are generated from prominent features, i.e., corner points and scale-invariant edges, for both endo-and epi-cardium segmentation. We adopt a level set formulation that integrates probabilistic priors with intensity, texture, and edge information for segmentation. Our experimental results show that with minimal user input, representative priors are correctly extracted from the data itself, and the proposed method is effective and robust for segmentation of the left ventricle myocardium even in images with very low contrast. More importantly, it avoids inter- and intra- observer variations and makes accurate quantitative analysis of low-quality cardiac MR images possible.


Empirical performance of a new user cohort method: lessons for developing a risk identification and analysis system.
Observational healthcare data offer the potential to enable identification of risks of medical products, but appropriate methodology has not yet been defined. The new user cohort method, which compares the post-exposure rate among the target drug to a referent comparator group, is the prevailing approach for many pharmacoepidemiology evaluations and has been proposed as a promising approach for risk identification but its performance in this context has not been fully assessed. To evaluate the performance of the new user cohort method as a tool for risk identification in observational healthcare data. The method was applied to 399 drug-outcome scenarios (165 positive controls and 234 negative controls across 4 health outcomes of interest) in 5 real observational databases (4 administrative claims and 1 electronic health record) and in 6 simulated datasets with no effect and injected relative risks of 1.25, 1.5, 2, 4, and 10, respectively. Method performance was evaluated through Area Under ROC Curve (AUC), bias, and coverage probability. The new user cohort method achieved modest predictive accuracy across the outcomes and databases under study, with the top-performing analysis near AUC >0.70 in most scenarios. The performance of the method was particularly sensitive to the choice of comparator population. For almost all drug-outcome pairs there was a large difference, either positive or negative, between the true effect size and the estimate produced by the method, although this error was near zero on average. Simulation studies showed that in the majority of cases, the true effect estimate was not within the 95 % confidence interval produced by the method. The new user cohort method can contribute useful information toward a risk identification system, but should not be considered definitive evidence given the degree of error observed within the effect estimates. Careful consideration of the comparator selection and appropriate calibration of the effect estimates is required in order to properly interpret study findings.


The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients.
Despite extensive research, no reliable biological marker for chronic fatigue syndrome (CFS) has yet been identified. However, hyperactivation of melanotrophs in the pituitary gland and increased levels of plasma alpha-melanocyte-stimulating hormone (alpha-MSH) have recently been detected in an animal model of chronic stress. Because CFS is considered to be caused partly by chronic stress events, increased alpha-MSH plasma levels may also occur in CFS patients. We therefore examined alpha-MSH levels in CFS patients. Fifty-five CFS patients, who were previously diagnosed within 10 years of with the disease, were enrolled in this study. Thirty healthy volunteers were studied as controls. Fasting bloods samples were collected in the morning and evaluated for their plasma levels of alpha-MSH, adrenocorticotropic hormone (ACTH), serum cortisol and dehydroepiandrosterone sulfate (DHEA-S). Mean levels of alpha-MSH were compared between the CFS and control groups using Welch's t test. The mean plasma alpha-MSH concentration in the CFS group (17.9 +/- 1.0 pg/mL) was significantly higher than that in healthy controls (14.5 +/- 1.0 pg/mL, p = 0.02). However, there was a wide range of values in the CFS group. The factors correlated with the plasma alpha-MSH values were analyzed using Spearman's rank correlation. A negative correlation was found between the duration of the CFS and the plasma alpha-MSH values (p = 0.04, rs = -0.28), but no correlations with ACTH, cortisol or DHEA-S levels were identified (p = 0.55, 0.26, 0.33, respectively). The CFS patients were divided into two groups: patients diagnosed for <or= 5 years' duration, and those diagnosed for 5-10 years' duration. They were compared with the healthy controls using one-way ANOVA and Tukey-Kramer multiple comparison tests. The mean alpha-MSH concentration in the <or= 5 years group was 20.8 +/- 1.2 pg/mL, which was significantly higher than that in the healthy controls (p < 0.01). There was no significant difference between the 5-10 year group (15.6 +/- 1.4 pg/mL) and the healthy controls. CFS patients with a disease duration of <or= 5 years had significantly higher levels of alpha-MSH in their peripheral blood. alpha-MSH could be a potent biological marker for the diagnosis of CFS, at least during the first 5 years after onset of the disease.


How widespread is stable protein S-nitrosylation as an end-effector of protein regulation?
Over the last 25 years protein S-nitrosylation, also known more correctly as S-nitrosation, has been progressively implicated in virtually every nitric oxide-regulated process within the cardiovascular system. The current, widely-held paradigm is that S-nitrosylation plays an equivalent role as phosphorylation, providing a stable and controllable post-translational modification that directly regulates end-effector target proteins to elicit biological responses. However, this concept largely ignores the intrinsic instability of the nitrosothiol bond, which rapidly reacts with typically abundant thiol-containing molecules to generate more stable disulfide bonds. These protein disulfides, formed via a nitrosothiol intermediate redox state, are rationally anticipated to be the predominant end-effector modification that mediates functional alterations when cells encounter nitrosative stimuli. In this review we present evidence and explain our reasoning for arriving at this conclusion that may be controversial to some researchers in the field.


Long-term tumor resistance induced by laser photo-immunotherapy.
An ideal treatment modality for metastasizing tumors should eradicate the primary tumor and elicit a systemic, tumor-selective response leading to elimination of metastases and long-term tumor resistance. Also, it should be induced by local treatment at the primary site, to limit adverse systemic effects. A new method for treating metastatic tumors which utilizes a combination of a near-infrared laser, a photosensitizer and an immunoadjuvant has been developed. It involves intra-tumor injection of the sensitizer/adjuvant solution, followed by local non-invasive laser irradiation. It has produced regression and total eradication of treated primary tumors and untreated metastases at remote sites against mammary tumors in rats. Successfully treated tumor-bearing rats showed total tumor resistance to subsequent tumor rechallenge. Our histochemical results showed that sera from cured tumor-bearing rats contained antibodies that bound strongly to the plasma membrane of both living and preserved tumor cells. Western blot analysis of tumor cell proteins using sera from successfully treated rats as the source of primary antibodies also showed distinct bands, indicating induction of tumor-selective antibodies. Our findings indicate that a systemic, long-term effect on metastatic tumors can be induced by local application of laser photo-immunotherapy.


Typing of Neisseria gonorrhoeae isolates by phenotypic and genotypic techniques in New Delhi, India.
The objective of this study is to investigate gonococcal isolates using phenotypic and genotypic methods. Sixty gonococcal isolates obtained were examined. Strains were divided into 9 resistant phenotypes: Chromosomally mediated penicillin-resistant Neisseria gonorrhoeae (CMRNGP), penicillinase-producing NG (PPNG), chromosomally mediated tetracycline-resistant NG (CMRNGT), TRNG, PPNG and TRNG, CMRNGPT, quinolone resistant NG (QRNG), Azithro R, and decreased susceptibility (DS) to ceftriaxone. These isolates were also subjected to auxotyping and NG-multi-antigen sequence typing (MAST). Of 60 isolates, 32 (53.33%) PPNG and only one was CMRNGP; 16 (26.66%) were CMRNGT, while 18 (30%) were TRNG. Both PPNG and TRNG found in 13 (21.66%) and none were CMRNGPT. QRNG was seen in 93.33%, 5% Azithromycin R, and 6.66% were DS to ceftriaxone. Based on auxotyping, 24 (40%) nonrequiring, 16 (26.66%) were proline requiring, 13 (21.66%) arginine requiring while 7 (11.66%) belonged to others. The most common ST was 6058 (32.5%). The discriminatory indices of antibiogram, auxotyping and NG-MAST were 0.77, 0.72, and 0.95, respectively. NG-MAST is the method of choice for epidemiological studies.


[Effect of heat injured keratinocytes supernatant on biological behavior of fibroblasts].
To observe the effect of the supernatant of heat injured keratinocytes (KC) on biological behavior of the dermal fibroblasts (Fb). Human dermal Fb were isolated and cultured. A model of heat injured KC (HaCaT) was reproduced in vitro. Supernatant of normal KC and the supernatant of KC culture 12 hours after heat injury were collected and diluted with non-serum DMEM in 1:1 volume ratio to make normal KC conditioned medium (NKCM) and heat injury KC conditioned medium (HKCM) respectively. Fb was respectively treated with non-serum DMEM and 2 kinds of conditioned medium. (1) The proliferation of Fb was detected with MTT method at post culture hour (PCH) 12, 24, 36, 48. (2) The apoptosis of Fb was determined by flow cytometry at PCH 12 (Fb were heat injured in advance; Fb without heat treatment was used as control). (3) At PCH 24, expression of a-SMA in Fb cytoplasm was determined with immunofluorescence method; expression of a-SMA mRNA in Fb was determined with real-time quantified PCR. Data were processed with one-way analysis of variance, and pairwise comparison among groups with LSD-t test. (1) The proliferation of Fb: the absorbance value of Fb cultured with HKCM at PCH 12, 24, 36, 48 was respectively higher than that of Fb cultured with non-serum DMEM (with t value respectively 1.89, 2.35, 2.02, 1.94, and P values all below 0.01). There were significant statistical differences between the absorbance values of Fb cultured with HKCM and those of Fb cultured with NKCM at PCH 12, 24, and 48 (at PCH 12, t = 1.83, P < 0.01; at PCH 24, t = 2.91, P < 0.05; at PCH 48, t = 1.83, P < 0.05). (2) Apoptosis of Fb cultured with HKCM was diminished as compared with that of Fb cultured with NKCM and of Fb without treatment (t = 3.31, P < 0.05; t = 1.47, P < 0.01). (3) The expression of alpha-SMA (red fluorescence) in Fb cultured with non-serum DMEM or NKCM was less as seen under fluorescence scope, and it was obviously increased in Fb cultured with HKCM. (4) The relative expression amount of alpha-SMA mRNA in Fb cultured with HKCM was 1.32 +/- 0.06, which was higher than that both in Fb cultured with NKCM (1.14 +/- 0.07, t = 2.51, P < 0.05) and in Fb cultured with non-serum DMEM (1.00 +/- 0.09, t = 1.77, P < 0.05). The supernatant of KC 12 hours after heat injury can obviously promote the proliferation of Fb, inhibit its apoptosis and accelerate transdifferentiation of Fb to myofibroblasts.


Multiple morbidity is associated with increased problems of food access in hospital: a cross-sectional survey utilising the Cumulative Illness Rating Scale.
Problems of undernutrition are common in hospital in-patients. Multiple morbidity increases with age and may contribute to nutritional risks. This research aimed to determine whether increased burden of long-term conditions is associated with patients' difficulties gaining access to food in hospital. A survey was implemented in 29 wards at four hospitals using a questionnaire measure of patients' experiences of food access and the Cumulative Illness Rating Scale (CIRS) to evaluate the burden of long-term illness in each patient. Experiences of food access were evaluated in relation to CIRS score category using random effects logistic regression to adjust for age group, sex and clustering by ward. Data were analysed for 764/1154 (66%) eligible participants, including 384 women. The median age was 60 years (range 18-96 years). CIRS scores were analysed using the categories 0 (104 patients), 1-3 (197), 4-6 (285), 7-9 (144) and ≥10 (34). When the CIRS was zero, 10% of patients experienced physical problems with food access, whereas, when the CIRS was ≥10, 41% experienced physical barriers to food access, adjusted odds ratio 3.65 (1.14-11.7, P = 0.029). Problems with food quality were experienced by 13% with CIRS = 0 and 32% with CIRS ≥ 10 (adjusted odds ratio 3.97, 1.35-11.6, P = 0.012). Participants with greater morbidity were more likely to report that depression, breathing difficulties or chewing and swallowing difficulties affected the amount of food that they ate at mealtimes. Patients with multiple morbidities are more vulnerable to experiencing physical barriers to accessing food and increased concerns with food quality. Assessing barriers to food access is particularly important in multiple morbidity.


Inflammatory Bowel Diseases: the genetic revolution.
The genetic component of Inflammatory Bowel Diseases is among the best known for complex genetic disorders. If the functional candidate gene approach was rarely fruitful in the past, genome-wide scans allowed finding several susceptibility genes for Crohn disease including NOD2, IL23R, ATG16L1, IRGM, TNFSF15, a region close to PTGER4, PTPN2, PTPN22, NKX2-3 and many others. Only one gene, ECM1, has been reported for ulcerative colitis alone. We now need to further explore these new genes before to understand their biological role. However they clearly demonstrate the importance of innate immunity and autophagy for Crohn's disease and of the TH-17 differentiation for ulcerative colitis, Crohn's disease and other inflammatory disorders.


Income inequality, social capital and self-rated health and dental status in older Japanese.
The erosion of social capital in more unequal societies is one mechanism for the association between income inequality and health. However, there are relatively few multi-level studies on the relation between income inequality, social capital and health outcomes. Existing studies have not used different types of health outcomes, such as dental status, a life-course measure of dental disease reflecting physical function in older adults, and self-rated health, which reflects current health status. The objective of this study was to assess whether individual and community social capital attenuated the associations between income inequality and two disparate health outcomes, self-rated health and dental status in Japan. Self-administered questionnaires were mailed to subjects in an ongoing Japanese prospective cohort study, the Aichi Gerontological Evaluation Study Project in 2003. Responses in Aichi, Japan, obtained from 5715 subjects and 3451 were included in the final analysis. The Gini coefficient was used as a measure of income inequality. Trust and volunteering were used as cognitive and structural individual-level social capital measures. Rates of subjects reporting mistrust and non-volunteering in each local district were used as cognitive and structural community-level social capital variables respectively. The covariates were sex, age, marital status, education, individual- and community-level equivalent income and smoking status. Dichotomized responses of self-rated health and number of remaining teeth were used as outcomes in multi-level logistic regression models. Income inequality was significantly associated with poor dental status and marginally significantly associated with poor self-rated health. Community-level structural social capital attenuated the covariate-adjusted odds ratio of income inequality for self-rated health by 16% whereas the association between income inequality and dental status was not substantially changed by any social capital variables. Social capital partially accounted for the association between income inequality and self-rated health but did not affect the strong association of income inequality and dental status.


Evaluation of immunogen delivery by DNA immunization using non-invasive bioluminescence imaging.
The efficacy of DNA vaccines is highly dependent on the methods used for their delivery and the choice of delivery sites/targets for gene injection, pointing at the necessity of a strict control over the gene delivery process. Here, we have investigated the effect of the injection site on gene expression and immunogenicity in BALB/c mice, using as a model a weak gene immunogen, DNA encoding firefly luciferase (Luc) delivered by superficial or deep injection with subsequent electroporation (EP). Immunization was assessed by monitoring the in vivo expression of luciferase by 2D- and 3D-bioluminescence imaging (BLI) and by the end-point immunoassays. Anti-Luc antibodies were assessed by ELISA, and T-cell response by IFN-γ and IL-2 FluoroSpot in which mouse splenocytes were stimulated with Luc or a peptide representing its immunodominant CD8+ T-cell epitope GFQSMYTFV. Monitoring of immunization by BLI identified EP parameters supporting the highest Luc gene uptake and expression. Superficial injection of Luc DNA followed by optimal EP led to a low level Luc expression in the mouse skin, and triggered a CD8+ T-cell response characterized by the peptide-specific secretion of IFN-γ and IL-2, but no specific antibodies. Intramuscular gene delivery resulted in a several-fold higher Luc expression and anti-Luc antibody, but induced low IL-2 and virtually no specific IFN-γ. Photon flux from the sites of Luc gene injection was inversely proportional to the immune response against GFQSMYTFV (p<0.05). Thus, BLI permitted to control the accuracy of gene delivery and transfection with respect to the injection site as well as the parameters of electroporation. Further, it confirmed the critical role of the site of DNA administration for the type and magnitude of the vaccine-specific immune response. This argues for the use of luminescent reporters in the preclinical gene vaccine tests to monitor both gene delivery and the immune response development in live animals.


Detection and treatment of an asymptomatic case of early esophageal cancer using chromoendoscopy and endoscopic mucosal resection.
Recent trends in the management of superficial esophageal cancer consist of improved detection and curative endoscopic therapy. However, successful endoscopic therapy has not been reported in Taiwanese patients with this disease. We describe the case of a male, 38-year-old habitual drinker admitted for a general health check-up, whose endoscopic examination revealed a slightly depressed discolored lesion in the middle esophagus. Chromoendoscopy with 3% Lugol's iodine solution showed a mesh-like unstained pattern occupying approximately two-thirds of the circumferential esophageal mucosa. Spraying with 2% toluidine blue solution stained a 3 x 6 cm suspect area pale blue. Endoscopic biopsy confirmed squamous cell carcinoma. Histopathologic examination revealed the lesion was a type IIc superficial esophageal cancer. Endoscopic ultrasonography showed the lesion was limited to the epithelial layer with no evidence of lymph node involvement. The lesion was removed en bloc using endoscopic mucosectomy. Microscopic examination of the resected specimen demonstrated that the depth of invasion was confined to the epithelial layer except for some areas with small nests of tumor cells within the lamina propria. Balloon dilatation to prevent post mucosectomy stricture was performed and the patient recovered uneventfully. At 1 year of follow-up, the patient was alive without any endoscopic signs of local recurrence. This case suggests that chromoendoscopy in combination with endoscopic resection is likely to benefit patients with early-stage esophageal cancer.


The mechanisms of cobalt chloride-induced protection against acetaminophen hepatotoxicity.
The mechanism by which cobalt chloride protects hamsters from acetaminophen-induced hepatotoxicity has been reexamined. In agreement with earlier studies, cobalt chloride treatment produced a 1.5-fold increase in hepatic glutathione levels and a decrease in the cytochrome P-450-dependent oxidative metabolism of acetaminophen. Cobalt chloride treatment also suppressed the sulfation while enhancing the glucuronidation of acetaminophen. The suppression of sulfation was most marked at low, non-hepatotoxic doses, whereas the enhancement of glucuronidation was greatest at higher hepatotoxic doses of acetaminophen. Collectively, the data suggest that the protective effect of cobalt chloride treatment on acetaminophen hepatotoxicity results from a combination of the suppression of the toxic pathway of cytochrome P-450 oxidation, an increase in the protective capacity of glutathione, and an enhancement of the nontoxic pathway of glucuronidation.


The Potential of L-Arginine in Prevention and Treatment of Disturbed Carbohydrate and Lipid Metabolism-A Review.
L-arginine, an endogenous amino acid, is a safe substance that can be found in food. The compound is involved in synthesis of various products responsible for regulatory functions in the body. Particularly noteworthy is, among others, nitric oxide, a signaling molecule regulating carbohydrate and lipid metabolism. The increasing experimental and clinical data indicate that L-arginine supplementation may be helpful in managing disturbed metabolism in obesity, regulate arterial blood pressure or alleviate type 2 diabetes symptoms, but the mechanisms underlying these effects have not been sufficiently elucidated. This review aims to present the up-to-date information regarding the current uses and health-promoting potential of L-arginine, its effects on nitric oxide, carbohydrate and lipid metabolisms, based on the results of in vivo, in vitro studies, and clinical human trials. Available literature suggests that L-arginine may have beneficial effects on human health. However, some studies found that higher dietary L-arginine is associated with worsening of an existing disease or may be potential risk factor for development of some diseases. The mechanisms of regulatory effects of L-arginine on carbohydrate and lipid metabolism have not been fully understood and are currently under investigation.


Effect of quality of life improvement on type 2 diabetes patients' self-esteem.
To study the effects of the quality of life (QoL) improvement on their QoL and self-esteem. This was a random controlled clinical trial study on 123 type 2 diabetes patients admitted to the Diabetes Clinic in Imam Khomeini Hospital at Ardebil, Iran from April 2009 to June 2010. The 30-70 years old participants are afflicted with type 2 diabetes, and randomly divided into 2 groups (experimental group n=61, and control group n=62). The questionnaires were composed of sociodemographic status, Farrel & Grant, and Rosenberg's self-esteem questionnaires and the quality of life (QoL) improvement plan was codified to educate and evaluate them. A p<0.05 was considered significant. Our study showed that subjects in the experimental group had low self-esteem (13%) before QOL training, and they had moderate self-esteem after the intervention (39%), however, the control group had moderate self-esteem (62.5%) in the pre-test, and changed to low self-esteem (12.9%) in the post-test, and there was significant difference in the previous and next intervention (p<0.05). The QoL improvement had positive effects on diabetic's self-esteem, and QOL as improved may help to reduce the side effects of type 2 diabetes process.


Non-coding RNAs regulation of macrophage polarization in cancer.
Noncoding RNA (ncRNA) transcripts that did not code proteins but regulate their functions were extensively studied for the last two decades and the plethora of discoveries have instigated scientists to investigate their dynamic roles in several diseases especially in cancer. However, there is much more to learn about the role of ncRNAs as drivers of malignant cell evolution in relation to macrophage polarization in the tumor microenvironment. At the initial stage of tumor development, macrophages have an important role in directing Go/No-go decisions to the promotion of tumor growth, immunosuppression, and angiogenesis. Tumor-associated macrophages behave differently as they are predominantly induced to be polarized into M2, a pro-tumorigenic type when recruited with the tumor tissue and thereby favoring the tumorigenesis. Polarization of macrophages into M1 or M2 subtypes plays a vital role in regulating tumor progression, metastasis, and clinical outcome, highlighting the importance of studying the factors driving this process. A substantial number of studies have demonstrated that ncRNAs are involved in the macrophage polarization based on their ability to drive M1 or M2 polarization and in this review we have described their functions and categorized them into oncogenes, tumor suppressors, Juggling tumor suppressors, and Juggling oncogenes.


Binding and cleavage of nucleic acids by the "hairpin" ribozyme.
The "hairpin" ribozyme derived from the minus strand of tobacco ringspot virus satellite RNA [(-)sTRSV] efficiently catalyzes sequence-specific RNA hydrolysis in trans (Feldstein et al., 1989; Hampel & Triz, 1989; Haseloff & Gerlach, 1989). The ribozyme does not cleave DNA. An RNA substrate analogue containing a single deoxyribonucleotide residue 5' to the cleavage site (A-1) binds to the ribozyme efficiently but cannot be cleaved. A DNA substrate analogue with a ribonucleotide at A-1 is cleaved; thus A-1 provides the only 2'-OH required for cleavage. These results support cleavage via a transphosphorylation mechanism initiated by attack of the 2'-OH of A-1 on the scissile phosphodiester. The ribozyme discriminates between DNA and RNA in both binding and cleavage. Results indicate that the 2'-OH of A-1 functions in complex stabilization as well as cleavage. The ribozyme efficiently cleaves a phosphorothioate diester linkage, suggesting that the pro-Rp oxygen at the scissile phosphodiester does not coordinate Mg2+.


Comparative Chemical Profiles and Phytotoxic Activity of Essential Oils of Two Ecospecies of Pulicaria undulata (L.) C.A.Mey.
The Asteraceae (Compositae) family is one of the largest angiosperm families that has a large number of aromatic species. Pulicaria undulata is a well-known medicinal plant that is used in the treatment of various diseases due to its essential oil (EO). The EO of both Saudi and Egyptian ecospecies were extracted via hydrodistillation, and the chemical compounds were identified by GC-MS analysis. The composition of the EOs of Saudi and Egyptian ecospecies, as well as other reported ecospecies, were chemometrically analyzed. Additionally, the phytotoxic activity of the extracted EOs was tested against the weeds Dactyloctenium aegyptium and Bidens pilosa. In total, 80 compounds were identified from both ecospecies, of which 61 were Saudi ecospecies, with a preponderance of β-pinene, isoshyobunone, 6-epi-shyobunol, α-pinene, and α-terpinolene. However, the Egyptian ecospecies attained a lower number (34 compounds), with spathulenol, hexahydrofarnesyl acetone, α-bisabolol, and τ--cadinol as the main compounds. The chemometric analysis revealed that the studied ecospecies and other reported species were different in their composition. This variation could be attributed to the difference in the environmental and climatic conditions. The EO of the Egyptian ecospecies showed more phytotoxic activity against D. aegyptium and B. pilosa than the Saudi ecospecies. This variation might be ascribed to the difference in their major constituents. Therefore, further study is recommended for the characterization of authentic materials of these compounds as allelochemicals against various weeds, either singular or in combination.


[SPECIFIC FEATURES OF LEGAL REGULATIONS OF ORGAN TRANSPLANTATION IN THE MOST DEVELOPED COUNTRIES].
The purpose of the article is to study the positive experience of the most developed countries in the field of transplantation and implementation of activities related to transplantation in order to determine possible ways to improve legal regulation in this area in Ukraine. It has been concluded that the formation and implementation of the state policy in the researched area is influenced by the model of consent for organs, tissue and cells transplantation introduced in the state, for example, the model of presumed consent (Spain), the model of donation or deed of gift (USA, Korea). It has been indicated that an effective infrastructure in the field of transplantation was formed in foreign countries; state authorities were created to coordinate the activities and manage the distribution, expansion and transplantation of "imported" organs. It has been offered to introduce such a positive experience of implementing transplantation into other countries of the world as: the availability of donors registration (USA, Korea), the exchange of information about donors and recipients (USA), the culture of organs donation (Spain), the implementation of propaganda and advertising activities on organs donation regulated at the legislative level (Spain), continuous professional development of medical employees involved in transplantation activities (Spain), the courtesy program for donors and support for their families (Korea), legislative norms on the protection of the rights of living donors (Spain, Korea).


Research Advances on the Interactions between Rabies Virus Structural Proteins and Host Target Cells: Accrued Knowledge from the Application of Reverse Genetics Systems.
Rabies is a lethal zoonotic disease caused by lyssaviruses, such as rabies virus (RABV), that results in nearly 100% mortality once clinical symptoms appear. There are no curable drugs available yet. RABV contains five structural proteins that play an important role in viral replication, transcription, infection, and immune escape mechanisms. In the past decade, progress has been made in research on the pathogenicity of RABV, which plays an important role in the creation of new recombinant RABV vaccines by reverse genetic manipulation. Here, we review the latest advances on the interaction between RABV proteins in the infected host and the applied development of rabies vaccines by using a fully operational RABV reverse genetics system. This article provides a background for more in-depth research on the pathogenic mechanism of RABV and the development of therapeutic drugs and new biologics.


Mutagenesis of tGCN5 core region reveals two critical surface residues F90 and R140.
Tetrahymena General Control Non-Derepressor 5 (tGCN5) is a critical regulator of gene transcription via acetylation of histones. Since the acetylation ability has been attributed to the "core region", we perform mutagenesis of residues within the tGCN5 "core region" in order to identify those critical for function and stability. Residues that do not participate in catalysis are identified, mutated and characterized for activity, structure and thermodynamic stability. Variants I107V, Q114L, A121T and A130S maintain the acetylation function relative to wild-type tGCN5, while variants F90Y, F112R and R140H completely abolish function. Of the three non-functional variants, since F112 is mutated into a non-homologous charged residue, a loss in function is expected. However, the remaining two variants are mutated into homologous residues, suggesting that F90 and R140 are critical for the activity of tGCN5. While mutation to homologous residue maintains acetylation of histone H3 for the majority of the variants, the two surface-exposed residues, F90 and R140, appear to be essential for tGCN5 function, structure or stability.


Pedobacter lentus sp. nov. and Pedobacter terricola sp. nov., isolated from soil.
Two Gram-negative, non-motile, pleomorphic bacterial strains, DS-40(T) and DS-45(T), were isolated from a soil sample collected from Dokdo, Korea, and their exact taxonomic positions were investigated by using a polyphasic approach. Strains DS-40(T) and DS-45(T) grew optimally at 25 degrees C and pH 6.5-7.5 in the presence of 0-1.0 % (w/v) NaCl. They contained MK-7 as the predominant menaquinone and possessed iso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 3 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH) as the major fatty acids. The DNA G+C contents of strains DS-40(T) and DS-45(T) were 36.0 and 36.8 mol%, respectively. Strains DS-40(T) and DS-45(T) shared a 16S rRNA gene sequence similarity of 96.7 % and demonstrated a mean DNA-DNA relatedness level of 12 %. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strains DS-40(T) and DS-45(T) were most closely phylogenetically affiliated with the genus Pedobacter of the family Sphingobacteriaceae. Strains DS-40(T) and DS-45(T) exhibited 16S rRNA gene sequence similarity values of 91.4-93.7 and 89.9-91.6 % with respect to the type strains of Pedobacter and Sphingobacterium species, respectively. Phenotypic and chemotaxonomic properties, together with the phylogenetic data, support the assignment of strains DS-40(T) and DS-45(T) as two distinct species within the genus Pedobacter. On the basis of phenotypic, phylogenetic and genetic data, strains DS-40(T) and DS-45(T) represent two novel species of the genus Pedobacter, for which the names Pedobacter lentus sp. nov. and Pedobacter terricola sp. nov. are proposed, respectively. The respective type strains are DS-40(T) (=KCTC 12875(T)=JCM 14593(T)) and DS-45(T) (=KCTC 12876(T)=JCM 14594(T)).


Effects of indomethacin on brain blood flow, cerebral metabolism, and sagittal sinus prostanoids after hypoxia.
We tested the hypotheses that during recovery from hypoxia, newborn piglets exhibit a posthypoxic cerebral hyperemia, indomethacin-pretreated piglets exhibit a posthypoxic cerebral hypoperfusion, and that the changes caused by indomethacin are dose dependent and related to the loss of prostanoids. We studied piglets exposed to 40 min of hypoxia after pretreatment with high (5 mg/kg, n = 9) or low (0.3 mg/kg, n = 8) doses of indomethacin or placebo (n = 9) and allowed to recover for 120 min. In the placebo and low-dose pretreatment groups, total and regional brain blood flow increased during hypoxia but returned to baseline 10 min after hypoxia. High-dose indomethacin pretreatment was associated with a posthypoxic hypoperfusion to certain brain regions at 10 min of recovery to values similar to those after indomethacin treatment before the onset of hypoxia. During and after hypoxia, the cerebral metabolic rate of oxygen was preserved in both the placebo and low-dose groups and decreased significantly during hypoxia in the high-dose group. Sagittal sinus prostacyclin was reduced significantly in both indomethacin-treated groups throughout the study. We conclude that a posthypoxic hyperemia is not observed in newborn piglets. This finding was not altered by pretreatment with a therapeutic dose of indomethacin, whereas a pharmacological dose was associated with selective hypoperfusion to certain brain regions both before hypoxia and during recovery from hypoxia.


Where is nursing in the electronic health care record?
The authors explore the possibilities for documenting professional nursing practice in an electronic health record. Recognizing that there are a variety of approaches to electronic documentation, the intent of this discussion is to generate a general rather than a particular approach to this issue. Nurses themselves must determine the ways in which professional nursing care will be captured in the electronic systems used in their facilities. Questions that arise from nursing include: How can nurses balance generalized care and protocol management with the need for documentation of each individual's nursing needs and particular experiences? How can the goals of nursing care be incorporated into the record? How can nursing actions/interventions be clearly communicated to all members of the health care team? In what ways can an electronic record document collaboration with the client to determine individualized outcomes of care and treatment? In considering these questions a number of issues arise: the selection of standardized languages to be used in the records, the title of the record, the tension between coding and text, the accessibility and transferability of the record, the ability to retrieve data on nursing outcomes through data mining techniques, ownership of the record, and privacy/security of the information stored. Although the paper will make no attempt to answer these questions it will draw on relevant journal articles to provide a context for this pivotal change in that way we account for health care practice.


Dynamic ligand exchange in reactions of samarium diiodide.
Mechanistic studies show the importance of iodide displacement by additives that accelerate reactions of samarium diiodide. The key feature important for acceleration of reaction rate is the use of proton donors and other additives that have a high enough affinity for Sm(II) to displace iodide yet do not saturate the coordination sphere inhibiting substrate reduction.


Verbal marking of affect by children with Asperger Syndrome and high functioning autism during spontaneous interactions with family members.
Verbal marking of affect by older children with Asperger Syndrome (AS) and high functioning autism (HFA) during spontaneous interactions is described. Discourse analysis of AS and HFA and typically developing children included frequency of affective utterances, affective initiations, affective labels and affective explanations, attribution of affective responses to self and others, and positive and negative markers of affect. Findings indicate that children with AS and HFA engaged in a higher proportion of affect marking and provided a higher proportion of affective explanations than typically developing children, yet were less likely to initiate affect marking sequences or talk about the affective responses of others. No significant differences were found between groups in terms of the marking of positive and negative affect.


Anaerobic bacterial endophthalmitis in the rabbit.
Anaerobic bacterial endophthalmitis was studied in rabbits following intravitreal injection of live Fusobacterium necrophorum. Clinical response, bacterial recovery, and histopathology were studied. An inoculum of approximately 50 organisms produced endophthalmitis in 59% of injected eyes, while 1000 or more organisms produced endophthalmitis in 100% of injected eyes. The course and severity of disease seemed to be independent of the concentration of bacteria above a minimal inoculum size. Affected eyes showed progressive endophthalmitis. Histopathologic changes corresponded to the clinical gradation of endophthalmitis, including progressive retinal necrosis.


Community-level characteristics associated with variation in rates of homelessness among families and single adults.
We modeled rates of family and single-adult homelessness in the United States in metropolitan and nonmetropolitan regions and as a function of community-level demographic, behavioral, health, economic, and safety net characteristics. We entered community-level characteristics and US Department of Housing and Urban Development point-in-time counts for a single night in January 2009 into separate mixed-effects statistical analyses that modeled homelessness rates for 4 subpopulations: families and single adults in metropolitan and nonmetropolitan regions. Community-level factors accounted for 25% to 50% of the variance in homelessness rates across models. In metropolitan regions, alcohol consumption, social support, and several economic indicators were uniquely associated with family homelessness, and drug use and homicide were uniquely associated with single-adult homelessness. In nonmetropolitan regions, life expectancy, religious adherence, unemployment, and rent burden were uniquely associated with family homelessness, and health care access, crime, several economic indicators, and receipt of Supplemental Security Income were uniquely associated with single-adult homelessness. Considering homeless families and single adults separately enabled more precise modeling of associations between homelessness rates and community-level characteristics, indicating targets for interventions to reduce homelessness among these subpopulations.


Introducing HIV/AIDS to South African health sciences students.
Given the burden of HIV/AIDS in South Africa, there is a need to introduce students to the issues health professionals face about the disease. We developed an introductory peer-led workshop on HIV/AIDS for first year students covering a range of biomedical and social issues. To evaluate the workshops, volunteer students were randomly allocated to participate in one of the workshops or not. At follow-up, students who participated in the workshops showed positive changes in their attitudes and skills regarding HIV. They were also more likely to feel empathy towards HIV-infected people and be more comfortable with the prospect of working with HIV-infected patients, compared to controls. This programme represents a platform for introducing a 'golden thread' of HIV/AIDS into health sciences curricula in countries profoundly affected by the epidemic.


Sheep from low-methane-yield selection lines created on alfalfa pellets also have lower methane yield under pastoral farming conditions.
Selection lines of sheep with low and high CH yield (g/kg DMI; CH/DMI) are being developed on the basis of feeding pelleted alfalfa hay at 2.0 times maintenance ME requirements in respiration chambers, but their divergence under predominant grazing conditions, as in New Zealand, is not known. The objectives of this study were to determine CH emissions and rumen fermentation characteristics in sheep from low and high CH/DMI selection lines while grazing pasture. Two grazing experiments were conducted with 42 selection line ewes in March 2013 (Exp. 1) and 98 selection line progeny ewe hoggets in October/November 2014 (Exp. 2), with CH emissions estimated by the SF tracer technique and DMI estimated by titanium oxide in combination with natural long-chain -alkanes. Total daily CH production (g/d) was similar between high and low CH/DMI selection line sheep in Exp. 1 and lower for low CH/DMI progeny compared with high CH/DMI progeny in Exp. 2 ( < 0.05). The CH/DMI tended to be 20% lower for low CH/DMI line sheep compared with high CH/DMI selection line sheep in Exp. 1 ( < 0.10) and was 15% lower for the low CH/DMI line in Exp. 2 ( < 0.01). Total VFA concentration and concentrations (m) of acetate, butyrate, and isobutyrate plus isovalerate were lower ( < 0.05) for low CH/DMI line sheep compared with high CH/DMI selection line sheep in both experiments. The current study indicates that differences in CH/DMI and VFA concentrations in selection line sheep, previously established on alfalfa pellets, are also present to a similar magnitude when grazing pasture.


CCL22-based peptide vaccines induce anti-cancer immunity by modulating tumor microenvironment.
CCL22 is a macrophage-derived immunosuppressive chemokine that recruits regulatory T cells through the CCL22:CCR4 axis. CCL22 was shown to play a key role in suppressing anti-cancer immune responses in different cancer types. Recently, we showed that CCL22-specific T cells generated from cancer patients could kill CCL22-expressing tumor cells and directly influence the levels of CCL22 in vitro. The present study aimed to provide a rationale for developing a CCL22-targeting immunotherapy. Vaccination with CCL22-derived peptides induced CCL22-specific T-cell responses in both BALB/c and C57BL/6 mice, assessed by interferon-γ secretion ex vivo. Anti-tumor efficacy of the peptides was evaluated in mouse models engrafted with syngeneic tumor models showing a reduced tumor growth and prolonged survival of the treated mice. Vaccination induced changes in the cellular composition of immune cells that infiltrated the tumor microenvironment assessed with multicolor flow cytometry. In particular, the infiltration of CD8+ cells and M1 macrophages increased, which increased the CD8/Treg and the M1/M2 macrophage ratio. This study provided preclinical evidence that targeting CCL22 with CCL22 peptide vaccines modulated the immune milieu in the tumor microenvironment. This modulation led to an augmentation of anti-tumor responses. This study provided a rationale for developing a novel immunotherapeutic modality in cancer.


The "flipped classroom" approach: Stimulating positive learning attitudes and improving mastery of histology among medical students.
Traditional medical education methodologies have been dramatically impacted by the introduction of new teaching approaches over the past few decades. In particular, the "flipped classroom" format has drawn a great deal of attention. However, evidence regarding the effectiveness of the flipped model remains limited due to a lack of outcome-based studies. In the present study, a pilot histology curriculum of the organ systems was implemented among 24 Traditional Chinese Medicine (TCM) students in a flipped classroom format at Jinan University. As a control, another 87 TCM students followed a conventional histology curriculum. The academic performance of the two groups was compared. In addition, a questionnaire was administered to the flipped classroom group. The test scores for the flipped classroom participants were found to be significantly higher compared to non-participants in the control group. These results suggest that students may benefit from using the flipped classroom format. Follow-up questionnaires also revealed that most of the flipped classroom participants undertook relatively more earnest preparations before class and were actively involved in classroom learning activities. The teachers were also found to have more class time for leading discussions and delivering quizzes rather than repeating rote didactics. Consequently, the increased teaching and learning activities contributed to a better performance among the flipped classroom group. This pilot study suggests that a flipped classroom approach can be used to improve histology education among medical students. However, future studies employing randomization, larger numbers of students, and more precise tracking methods are needed before definitive conclusions can be drawn. Anat Sci Educ 10: 317-327. © 2016 American Association of Anatomists.


[Demographic factors and pregnancy--who chooses abortion?].
The number of pregnancies terminated as induced abortions has been analysed from data recorded in the Norwegian Birth Registry and the Norwegian Abortion File at the Central Bureau of Statistics. During the time period 1 January 1979 to 31 December 1991, 871,439 pregnant women were registered. Among single women the proportion of pregnancies terminated as induced abortions varied between 40 and 75% throughout the study period. Cohabitant women chose abortion significantly more often than married women. Among married women the proportion of pregnancies interrupted varied with the woman's age and the number of children. Among women 20-34 years of age with one or no child, more than 97% of the pregnancies proceeded to term. Women undergoing abortion comprise a heterogeneous group, judged by demographic factors. Future studies must focus on social factors as well as demographic factors, in order to uncover the complexity of the reasons for choosing abortion.


Use of Contrast-Enhanced Ultrasound in Carotid Atherosclerotic Disease: Limits and Perspectives.
Contrast-enhanced ultrasound (CEUS) has recently become one of the most versatile and powerful diagnostic tools in vascular surgery. One of the most interesting fields of application of this technique is the study of the carotid atherosclerotic plaque vascularization and its correlation with neurological symptoms (transient ischemic attack, minor stroke, and major stroke) and with the characteristics of the "vulnerable plaque" (surface ulceration, hypoechoic plaques, intraplaque hemorrhage, thinner fibrous cap, and carotid plaque neovascularization at histopathological analysis of the sample after surgical removal). The purpose of this review is to collect all the original studies available in literature (24 studies with 1356 patients enrolled) and to discuss the state of the art, limits, and future perspectives of CEUS analysis. The results of this work confirm the reliability of this imaging study for the detection of plaques with high risk of embolization; however, a shared, user-friendly protocol of imaging analysis is not available yet. The definition of this operative protocol becomes mandatory in order to compare results from different centers and to validate a cerebrovascular risk stratification of the carotid atherosclerotic lesions evaluated with CEUS.


Non-connected versus interconnected macroporosity in poly(2-hydroxyethyl methacrylate) polymers. An X-ray microtomographic and histomorphometric study.
Poly(2-hydroxyethyl methacrylate) (pHEMA) has potentially broad biomedical applications: it is biocompatible and has a hardness comparable to bone when bulk polymerized. Porous biomaterials allow bone integration to be increased, especially when the pores are interconnected. In this study, three types of porogens (sugar fibers, sucrose crystals, and urea beads) have been used to prepare macroporous pHEMA. The pore volume and interconnectivity parameters of the porosity were measured by X-ray microtomography and image analysis. Sucrose crystals, having a high volumetric mass, gave large pores that were located on the block sides. Urea beads and sugar fibers provided pores with the same star volume (2.65 +/- 0.46 mm3 and 2.48 +/- 0.52 mm3, respectively) but which differed in interconnectivity index, fractal dimension, and Euler-Poincarés number. Urea beads caused non-connected porosity, while sugar fibers created a dense labyrinth within the polymer. Interconnectivity was proved by carrying out surface treatment of the pHEMA (carboxymethylation in water), followed by von Kossà staining, which detected the carboxylic groups. Carboxymethylated surfaces were observed on the sides of the blocks and on the opened or interconnected pores. The disconnected pores were unstained. Macroporous polymers can be prepared with water-soluble porogens. X-ray microtomography appears a useful tool to measure porosity and interconnectedness.


SLC25A22 Promotes Proliferation and Metastasis of Osteosarcoma Cells via the PTEN Signaling Pathway.
Osteosarcoma is a highly malignant bone tumor. However, due to the high complexity of the occurrence and metastasis of osteosarcoma, the exact mechanism promoting its development and progression remains to be elucidated. This study highlights the causal link between solute carrier family 25 member 22 (SLC25A22) and the development, progression, and metastasis of osteosarcoma. SLC25A22 is upregulated in human osteosarcoma and predicts a poor prognosis. The upregulation of SLC25A22 in osteosarcoma tissues was significantly associated with cell proliferation, invasion, and metastasis. Studies of functional gain (overexpression) and loss (knockdown) showed that SLC25A22 significantly increases the ability of osteosarcoma cells to proliferate, as well as invade and metastasize in vitro. At the same time, the expression of SLC25A22 promoted the progression of the cellcycle of osteosarcoma cell lines and inhibited the apoptosis of osteosarcoma cells. Analysis using a mouse xenograft model showed that xenografts of SLC25A22 stable overexpressing osteosarcoma cells had a significant increase in tumor volume and weight compared to the control group. Lung metastasis models in mice showed that expression of SLC25A22 promoted lung metastasis of osteosarcoma in vivo. Furthermore, SLC25A22 inhibited phosphatase and tensin homolog expression and increased phosphorylation of protein kinase b (Akt) and Focal Adhesion Kinase (FAK) in the phosphatase and tensin homolog signaling pathway. In summary, SLC25A22 is highly expressed in osteosarcoma, promoting osteosarcoma cell proliferation and invasion by inhibiting the phosphatase and tensin homolog signaling pathway.


Dynamic structure of the calmodulin-binding domain of the plasma membrane Ca-ATPase in native erythrocyte ghost membranes.
We have used frequency-domain fluorescence resonance energy transfer (FRET) and anisotropy measurements to identify the structural properties of wheat germ calmodulin (CaM) bound to either the plasma membrane Ca-ATPase (PM-Ca-ATPase) in native erythrocyte ghost membranes or a peptide (C25W) that has an identical sequence to the CaM-binding domain on the PM-Ca-ATPase. Cross-linking experiments using benzophenone labeled CaM in conjunction with immunoblots using antibodies specific for either CaM or the PM-Ca-ATPase indicate that one molecule of CaM selectively binds one PM-Ca-ATPase polypeptide chain in native erythrocyte ghost membranes. There are no other proteins in the erythrocyte membrane that bind CaM with high affinity, permitting the measurement of the structural properties of CaM bound to the PM-Ca-ATPase in native erythrocyte ghost membranes. FRET measurements between the fluorophore pyrene maleimide (PMal) located at Cys27 in calcium binding loop I and nitrotyrosine139 in calcium binding loop IV on wheat germ CaM indicate that the average spatial separation and conformational heterogeneity associated with the two opposing globular domains of CaM are virtually identical upon CaM binding to either the PM-Ca-ATPase or C25W. Measurements of the solvent accessibility and segmental rotational dynamics of PMal-CaM bound to either the PM-Ca-ATPase or C25W further indicate that the local environment around the pyrene label located at Cys27 is very similar. However, the overall rotational dynamics of CaM bound to the PM-Ca-ATPase is much slower (phi 2 = 83 +/- 14 ns) than observed when CaM binds C25W (phi 2 = 10.3 +/- 0.5 ns). This implies that CaM is tightly associated with the CaM-binding domain of the PM-Ca-ATPase and that the observed rotational motion of pyrenylmaleimide labeled CaM is characteristic of the global motion of the CaM-binding domain on the PM-Ca-ATPase. The similar conformational heterogeneity and local environment of CaM bound to either the PM-Ca-ATPase or C25W indicates that CaM binds to a contiguous sequence of amino acids on the Ca-ATPase that are analogous to C25W and that there are no significant interactions with other structural elements within the PM-Ca-ATPase. The rate of rotational motion associated with CaM bound to the PM-Ca-ATPase is consistent with hydrodynamic calculation in which the calmodulin-binding domain located at the carboxyl-terminus of the PM-Ca-ATPase has a stable and defined tertiary structure that is independent of the other cytoplasmic domains of the PM-Ca-ATPase.