Simple green production of silver nanoparticles facilitated by bacterial genomic DNA and their antibacterial activity.
Green synthesis of AgNPs has gained many research interests as a low cost and eco-friendly approach. This work reported on the use of bacterial genomic DNA as the alternative biopolymer for a green production of AgNPs under a neutral pH. Although both ssDNA and dsDNA could function as stabilizing agents during the synthesis process, the ssDNA, generated by pre-heating the dsDNA at 100 °C, was more efficient to produce AgNPs with higher yield as determined by the intensity of the surface plasmon resonance (SPR) peak of silver at 475 nm. The obtained AgNPs were spherical with the average diameter of 15.0 ± 7.6 nm, which their identity was confirmed by X-ray diffraction, high-resolution transmission electron microscopy, and selected area electron diffraction analyses. The synthesized AgNPs exhibited the potent antibacterial activity against both Escherichia coli and Staphylococcus aureus with the minimum bactericidal concentrations at 250 and 500 μg/ml, respectively, suggesting their potential antibacterial activity against both Gram-negative and Gram-positive bacteria.


A Study of Cytokeratin-7 Expression and Clinicopathological Correlation in Dysplasia and Squamous Cell Carcinoma of the Cervix.
Cytokeratin (CK) proteins play a vital role in cancer diagnosis, of which,CK-7 is a prominent marker of squamocolumnar junction cells corresponding to the the initiating site of cervical cancer.The current study is aimed to evaluate the expression pattern of CK-7 and to corelate with the clinicopathological features in patients with cervical dysplasia and invasive squamous cell carcinoma. The hysterectomy and biopsy specimens from women with cervical dysplasia (n=60) and carcinoma (n=60) were evaluated histopathologically and processed for immunohistochemistry (IHC) staining to assess for CK-7 expression. The relationship between CK-7 expression and tumor characteristics like histological type of cervical intraepithelial neoplasia (CIN), tumor type and grade was evaluated. Data was analyzed using the Chi-square test ,wherein the p value ≤ 0.05 were taken for statistical significance. Positive CK-7 expression was observed in 25 (41.67%) dysplasia and in 34 (56.67%) carcinoma cases. Majority of the cases were CIN III (n=31, 51.67%), large cell non-keratinizing tumor type (n=54, 90%) and moderately differentiated grade of tumor (n=52, 86.67%), out of which 18 (58.1%), 34 (62.96%) and 30 (57.69%) cases were CK-7 positive, respectively. The difference in clinical diagnosis and tumor characteristics over CK-7 expression was significant (p<0.05). The pattern of CK-7 expression in dysplasia and carcinoma cases were diffuse in 23 (38.33%) and 31 (51.67%) respectively and patchy in 2 (3.33%) and 3 (5%) of them, respectively. Significant positive CK-7 expression in cervical dysplasia and carcinoma indicates a good clinical course and its role as a useful predictable marker for cancer progression.


Neovascular fundus abnormalities in peripheral uveitis.
Neovascular fundus abnormalities are an unusual complication of peripheral uveitis. Peripheral retinal neovascularization was seen in 11 patients, six of whom had retinal angioma-like lesions. Most of the patients had loss of vision caused by vitreous hemorrhage. In four additional patients with peripheral uveitis, neovascularization developed either at the disc or elsewhere in the posterior pole.


The effect of familiarity on within-person age judgements from voices.
Listeners can perceive a person's age from their voice with above chance accuracy. Studies have usually established this by asking listeners to directly estimate the age of unfamiliar voices. The recordings used mostly include cross-sectional samples of voices, including people of different ages to cover the age range of interest. Such cross-sectional samples likely include not only cues to age in the sound of the voice but also socio-phonetic cues, encoded in how a person speaks. How age perpcetion accuracy is affected when minimizing socio-phonetic cues by sampling the same voice at different time points remains largely unknown. Similarly, with the voices in age perception studies being usually unfamiliar to listeners, it is unclear how familiarity with a voice affects age perception. We asked listeners who were either familiar or unfamiliar with a set of four voices to complete an age discrimination task: listeners heard two recordings of the same person's voice, recorded 15 years apart, and were asked to indicate in which recording the person was younger. Accuracy for both familiar and unfamiliar listeners was above chance. While familiarity advantages were apparent, accuracy was not particularly high: familiar and unfamiliar listeners were correct for 68.2% and 62.7% of trials, respectively (chance = 50%). Familiarity furthermore interacted with the voices included. Overall, our findings indicate that age perception from voices is not a trivial task at all times - even when listeners are familiar with a voice. We discuss our findings in the light of how reliable voice may be as a signal for age.


Rise of the Pigs: Utilization of the Porcine Model to Study Musculoskeletal Biomechanics and Tissue Engineering During Skeletal Growth.
Large animal models play an essential role in the study of tissue engineering and regenerative medicine (TERM), as well as biomechanics. The porcine model has been increasingly used to study the musculoskeletal system, including specific joints, such as the knee and temporomandibular joints, and tissues, such as bone, cartilage, and ligaments. In particular, pigs have been utilized to evaluate the role of skeletal growth on the biomechanics and engineered replacements of these joints and tissues. In this review, we explore the publication history of the use of pig models in biomechanics and TERM discuss interspecies comparative studies, highlight studies on the effect of skeletal growth and other biological considerations in the porcine model, and present challenges and emerging opportunities for using this model to study functional TERM.


[Relationship of cyclooxygenase-2 and multidrug resistance associated factors to chemosensitivities in gastrointestinal carcinomas].
To investigate the relationship of cyclooxygenase-2 (COX-2), p-glycoprotein(P-gp), glutathione S-transferase-pi (GST-pi), and topoisomerase II alpha (Topo II alpha) to chemosensitivities in gastrointestinal tract carcinomas. The tumor tissue samples were collected from 84 specimens of gastrointestinal carcinomas. The expressions of COX-2, P-gp, GST-pi, and Topo II alpha were determined immunohistochemically. The chemosenisitivity of each sample to 9 drugs were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The positive rates of COX-2, P-gp, GST-pi and Topo II alpha were 48.8%, 76.2%, 78.6% and 66.7% respectively. The expression of COX-2 was correlated with the expression of P-gp and Topo II alpha significantly (r = 0.287, 0.256, both P < 0.05). In terms of relationships of four MDR-related factors expression to inhibition rate of tumor cells, the inhibition rates of PTX, eADM and OPT in COX-2 strong expression group were significantly lower than those in COX-2 weak expression group (t = 2.21, 3.11, 2.09; all P < 0.05). The inhibition rates of PTX, OXA and DDP in P-gp strong expression group were lower than those in weak group (t = 2.54, 2.47, 2.05; all P < 0.05). There were lower inhibition rates for 5-Fu in GST-pi strong expression group (t = 2.13, P < 0.05), and higher inhibition rates for VCR, PTX and eADM in TopoII alpha strong expression group (t = -2.29, -2.12, - 2.26, all P < 0.05). The overexpressions of MDR-related factors in gastrointestinal carcinomas were only associated with the chemosensitivity to some of the chemotherapeutic agents, but not all. MDR related factors may be not specific and accurate predictors for the clinical chemosensitivity.


American Indian and Alaska Native veterans in the Indian Health Service: Health status, utilization, and cost.
Many rural American Indian and Alaska Native (AIAN) veterans receive care from the Indian Health Service (IHS). United States Department of Veterans Affairs (VA) has reimbursement agreements with some IHS facilities and tribal programs and seeks to expand community partnerships in tribal areas, but details of how AIAN veterans use IHS are unknown. We aimed to assess the health status, service utilization patterns, and cost of care of veterans who use IHS. We used comprehensive and integrated IHS data to compare health status, health service utilization and treatment cost of veterans (n = 12,242) to a matched sample of non-veterans (n = 12,242). We employed logistic, linear, or negative binomial regressions as appropriate, by sex and overall. Compared to non-veterans, veterans had lower odds of having hypertension, renal disease, all-cause dementia, and alcohol or drug use disorders, but had similar burden of other conditions. In service utilization, veterans had lower hospital inpatient days; patterns were mixed across outpatient services. Unadjusted treatment costs for veterans and non-veterans were $3,923 and $4,145, respectively; veteran adjusted treatment costs were statistically lower. Differences in significance by sex were found for health conditions and service use. AIAN veterans, compared to AIAN non-veterans, were not less healthy, nor did they require more intensive or more costly care under IHS. Our results indicate the viability and importance of expanding IHS-VA partnerships in community care.


The effectiveness of potent dental adhesives on the viability of LPS challenged human gingival fibroblasts.
Dental adhesives are necessary for the retention of specific dental restorations utilized to repair the anatomy of the tooth after dental decay is removed. Adhesives come into contact with healthy and diseased periodontal tissues. Porphyromonas gingivalis is a gram negative bacterial pathogen, and lipopolysaccharide (LPS-PG) is an endotoxin found in gingival connective tissues of patients who suffer from periodontal disease. The presence of the endotoxin causes inflammation. This study aims to evaluate the effectiveness of potent dental adhesives when human gingival fibroblasts are challenged with LPS-PG. The fibroblasts were exposed to the dental adhesives polymethly methacrylate (PMMA), OptiBond®, and Prime & Bond® which were purchased from Patterson Dental, a national dental materials supplier. The human gingival fibroblasts (HGF-1, ATCC® CRL-2014™) were purchased from American Type Culture Collection (ATCC). The porphyromonas gingival lipopolysaccharide (LPS-PG) was purchased from Fisher Scientific (Pittsburg, PA). No significant differences in metabolic behavior was detected among the groups (p<0.132). While the glutathione assay determined that there was not any significant increase in oxidative stress levels; the lactate dehydrogenase assay identified significant cellular damage in the group exposed to combinations of the Prime & Bond® adhesives and LPS-PG at 48 hour intervals (p<0.003). No significant changes were noted in cellular morphology at any phases, and all cells demonstrated typical fibroblast spindle shape.


Selection and Validation of Appropriate Reference Genes for qRT-PCR Analysis in Isatis indigotica Fort.
Due to its sensitivity and specificity, real-time quantitative PCR (qRT-PCR) is a popular technique for investigating gene expression levels in plants. Based on the Minimum Information for Publication of Real-Time Quantitative PCR Experiments (MIQE) guidelines, it is necessary to select and validate putative appropriate reference genes for qRT-PCR normalization. In the current study, three algorithms, geNorm, NormFinder, and BestKeeper, were applied to assess the expression stability of 10 candidate reference genes across five different tissues and three different abiotic stresses in Isatis indigotica Fort. Additionally, the IiYUC6 gene associated with IAA biosynthesis was applied to validate the candidate reference genes. The analysis results of the geNorm, NormFinder, and BestKeeper algorithms indicated certain differences for the different sample sets and different experiment conditions. Considering all of the algorithms, PP2A-4 and TUB4 were recommended as the most stable reference genes for total and different tissue samples, respectively. Moreover, RPL15 and PP2A-4 were considered to be the most suitable reference genes for abiotic stress treatments. The obtained experimental results might contribute to improved accuracy and credibility for the expression levels of target genes by qRT-PCR normalization in I. indigotica.


Pitx genes are redeployed in adult myogenesis where they can act to promote myogenic differentiation in muscle satellite cells.
Skeletal muscle retains a resident stem cell population called satellite cells. Although mitotically quiescent in mature muscle, satellite cells can be activated to produce myoblast progeny to generate myonuclei for skeletal muscle homoeostasis, hypertrophy and repair. Regulation of satellite cell function in adult requires redeployment of many of the regulatory networks fundamental to developmental myogenesis. Involved in such control of muscle stem cell fate in embryos are members of the Pitx gene family of bicoid-class homeodomain proteins. Here, we investigated the expression and function of all three Pitx genes in muscle satellite cells of adult mice. Endogenous Pitx1 was undetectable, whilst Pitx2a, Pitx2b and Pitx2c were at low levels in proliferating satellite cells, but increased during the early stages of myogenic differentiation. By contrast, proliferating satellite cells expressed robust amounts of Pitx3, with levels then decreasing as cells differentiated, although Pitx3 remained expressed in unfused myoblasts. To examine the role of Pitx genes in satellite cell function, retroviral-mediated expression of Pitx1, all Pitx2 isoforms or Pitx3, was used. Constitutive expression of any Pitx isoform suppressed satellite cell proliferation, with the cells undergoing enhanced myogenic differentiation. Conversely, myogenic differentiation into multinucleated myotubes was decreased when Pitx2 or Pitx3 levels were reduced using siRNA. Together, our results show that Pitx genes play a role in regulating satellite cell function during myogenesis in adult.


Problem and solution: the spiritual dimension of clergy sexual abuse and its impact on survivors.
In this paper, we offer a way to understand the spiritual dimension of clergy-perpetrated sexual abuse. Spirituality is defined as a search for the sacred--a process of discovery, conservation, and transformation that evolves over the lifespan. We describe the ways in which clergy-perpetrated sexual abuse impacts negatively on the individual's search for the sacred and the ways in which spirituality can serve as a valuable resource for survivors. We then consider how clinicians can draw on the client's spirituality as a source of solutions to problems and how clinicians can address the spiritual problems raised by clergy-perpetrated sexual abuse. Perhaps the greatest challenge for mental health professionals is to become better acquainted with the multifaceted nature of spiritual life.


Palladium-Catalyzed Atroposelective Kinetic C-H Olefination and Allylation for the Synthesis of C-B Axial Chirality.
The direct C-H functionalization of 1,2-benzazaborines, especially asymmetric version, remains a great challenge. Here we report a palladium-catalyzed enantioselective C-H olefination and allylation reactions of 1,2-benzazaborines. This asymmetric approach is a kinetic resolution (KR), providing various C-B axially chiral 2-aryl-1,2-benzazaborines and 3-substituted 2-aryl-1,2-benzazaborines in generally high yields with excellent enantioselectivities (selectivity (S) factor up to 354). The synthetic potential of this reaction is showcased by late-stage modification of complex molecules, scale-up reaction, and applications.


Brain-Specific Oxysterols and Risk of Schizophrenia in Clinical High-Risk Subjects and Patients With Schizophrenia.
Accumulating evidence from clinical, genetic, and epidemiologic studies suggest that schizophrenia might be a neuronal development disorder. While oxysterols are important factors in neurodevelopment, it is unknown whether oxysterols might be involved in development of schizophrenia. The present study investigated the relationship between tissue-specifically originated oxysterols and risk of schizophrenia. A total of 216 individuals were recruited in this study, including 76 schizophrenia patients, 39 clinical high-risk (CHR) subjects, and 101 healthy controls (HC). We investigated the circulating levels of brain-specific oxysterol 24(S)-hydroxycholesterol (24OHC) and peripheral oxysterol 27-hydroxycholesterol (27OHC) in all participants and analyzed the potential links between the oxysterols and specific clinical symptoms in schizophrenic patients and CHR. Our data showed an elevation of 24OHC in both schizophrenia patients and CHR than that in HC, while a lower level of 27OHC in the schizophrenia group only. The ratio of 24OHC to 27OHC was only increased in the schizophrenic group compared with CHR and HC. For the schizophrenic patients, the circulating 24OHC levels are significantly associated with disease duration, positively correlated with the positive and negative syndrome total scores, while the 27OHC levels were inversely correlated with the positive symptom scores. Together, our data demonstrated the disruption of tissue-specifically originated cholesterol metabolism in schizophrenia and CHR, suggesting the circulating 24OHC or 24OHC/27OHC ratio might not only be a potential indicator for risk for schizophrenia but also be biomarkers for functional abnormalities in neuropathology of schizophrenia.


Configural and contextual prioritization in object-based attention.
When attention is directed to a location within an object, other locations within that object also enjoy an attentional advantage. Recently we demonstrated that this object-based advantage is mediated by increased attentional priority assigned to locations within an already attended object and not to early sensory enhancement due to the "spread" of attention within the attended object (Shomstein & Yantis, 2002). At least two factors might contribute to the assignment of attentional priority, one related to the configuration of objects in a scene and the other related to the probability of target appearance in each location imposed by task contingencies. We investigated the relative contribution of these factors by cuing one end of one of a pair of rectangles; a subsequent target appeared most often in the cued location. We manipulated attentional priority setting by varying (1) the probability that a target would appear in each of two uncued locations and (2) the cue to target stimulus onset asynchrony (SOA). On invalidly cued trials, the target appeared in the high-probability location (defined by an absolute spatial location, e.g., upper right) 83% of the time and in the low-probability location (e.g., lower left) 17% of the time. In both conditions, uncued targets appeared in the cued object half the time and in the uncued object half the time. At short SOAs, the same-object and probability effects were approximately additive. However, at longer SOAs, the same-object effects disappeared, and reaction times depended exclusively on location probability. These results suggest that observers adopt an implicit configural scanning strategy (in which unattended locations within an attended object have high priority) or an implicit contextual scanning strategy (in which objectively high-probability locations have high priority) depending on task contingencies and the amount of time that is available to deploy attention.


Modern coronary rehabilitation. New concepts in care.
Contemporary rehabilitative care for coronary patients involves individualized recommendations and applications. The challenge to the physician is to select those services that are appropriate for a given patient, on the basis of both medical recommendations and patient preferences, so as to encourage progressive independence in rehabilitative care. The physician, patient, and rehabilitation professional can then define the desired outcome of each intervention, in both a quantitative and a time-based format. Physical activity goals can often be rapidly met, whereas risk reduction addresses longer-term outcomes. Exercise test-based risk stratification can identify the high-risk subset of coronary patients, who require supervision of exercise testing, often with ECG monitoring. Low-risk patients can exercise independently. Modest-intensity dynamic exercise is beneficial and has greater adherence and safety than high-intensity exercise. Isometric exercise is recommended once patients attain a reasonable dynamic (aerobic) exercise capacity. Education and counseling are necessary to implement reduction of coronary risk factors. Technological advances that may help in delivery of educational services include videocassettes and computer interactive programs for home use. Information shared with family members has added benefit, because they may also have coronary risk attributes. Innovative approaches may improve the effectiveness and efficiency of long-term rehabilitative care.


Quantifying the trade-off between parameter and model structure uncertainty in life cycle impact assessment.
To enhance the use of quantitative uncertainty assessments in life cycle impact assessment practice, we suggest to quantify the trade-off between parameter uncertainty, i.e. any uncertainty associated with data and methods used to quantify the model parameters, and model structure uncertainty, i.e. the uncertainty about the relations and mechanisms being studied. In this paper we show the trade-off between the two types of uncertainty in a case of maize production with a focus on freshwater ecotoxicity due to pesticide application in The Netherlands. Parameter uncertainty in pesticide emissions, chemical-specific data, effect and damage data, and fractions of metabolite formation of degradation products was statistically quantified via probabilistic simulation, i.e. Monte Carlo simulation. Model structure uncertainties regarding the concentration-response model to be included, the selection of the damage model, and the inclusion of pesticide transformation products were assessed via discrete choice analysis. We conclude that to arrive at a minimum level of overall uncertainty the linear concentration-response model is preferable, while the transformation products may be excluded. Selecting the damage model has a relatively low influence on the overall uncertainty. Our study shows that quantifying the trade-off between different types of uncertainty can help to identify optimal model complexity from an uncertainty point of view.


[Coexistence of pulmonary tuberculosis and alcoholism in Poland].
The aim of study was to determine a number of alcoholics in new diagnosed cases of bacteriological confirmed pulmonary tuberculosis in 1989-1990. Data were obtained from the Central Register of Tuberculosis. It was found that the number of alcoholics among new registered patients with tuberculosis increased from 8.8% to 10.5%. Young patients were more than 60% group. Results of treatment of severe types of pulmonary tuberculosis in alcoholics were also not so effective as in typical patients.


Effects of Myxococcus fulvus KYC4048 Metabolites on Breast Cancer Cell Death.
Using MCF7 breast cancer cells, we tested the anticancer activity of metabolites from 130 strains of myxobacteria newly isolated in South Korea. Of these, three strains whose metabolites had high anticancer activity and low cell toxicity were selected and identified by their fruiting body morphology, cell morphology, and 16S rRNA sequence. Strains KYC4030 and KYC4048 were determined to be Myxococcus fulvus, whereas strain KYC4081 was identified as Corallococcus coralloides. We found that metabolites of M. fulvus KYC4048 demonstrated no toxicity in normal cells but specifically induced cancer cell death by suppressing the expression of WNT2B. This discovery highlights the value of assessing the metabolic and biomedical potential of myxobacteria, even those that are already known but were isolated from new areas, and the possible use of metabolites from M. fulvus KYC4048 in cancer treatment.


Epithelial sodium channel is involved in H2S-induced acute pulmonary edema.
Acute pulmonary edema is one of the major outcomes of exposure to high levels of hydrogen sulfide (H2S). However, the mechanisms involved in H2S-induced acute pulmonary edema are still poorly understood. Therefore, the present study is designed to evaluate the role of epithelial sodium channel (ENaC) in H2S-induced acute pulmonary edema. The Sprague-Dawley rats were exposed to sublethal concentrations of inhaled H2S, then the pulmonary histological and lung epithelial cell injury were evaluated by hematoxylin-eosin staining and electron microscopy, respectively. In addition to morphological investigation, our results also revealed that H2S exposure significantly decreased the alveolar fluid clearance and increased the lung tissue wet-dry ratio. These changes were demonstrated to be associated with decreased ENaC expression. Furthermore, the extracellular-regulated protein kinases 1/2 pathway was demonstrated to be implicated in H2S-mediated ENaC expression, because PD98059, an ERK1/2 antagonist, significantly mitigated H2S-mediated ENaC down-regulation. Therefore, our results show that ENaC might represent a novel pharmacological target for the treatment of acute pulmonary edema induced by H2S and other hazardous gases.


The effects of ultraviolet C on in vitro nucleosome assembly and stability.
The effects of ultraviolet C (UVC) irradiation on nucleosome assembly and its stability were investigated quantitatively using an in vitro nucleosome assembly system comprising a plasmid DNA of pBR322 and core histones isolated from rat ascites hepatoma cells. Nucleosomal formation was estimated by analyzing the resulting DNA supercoils. When UVC-irradiated (3000 J/m2) DNA was used as a substrate for the nucleosome assembly system, the nucleosomal formation efficiency was reduced by half compared with nonirradiated DNA. On the other hand, when the reconstituted nucleosomes (minichromosomes) on the nonirradiated DNA were irradiated with UVC (3000 J/m2), about half each were disrupted and retained. These results indicate that it is difficult for UV-damaged DNA regions to supercoil around the histone octamers to form nucleosomes and that the histone octamers in the UV-damaged nucleosomes tend to be dissociated from DNA.


Distributed control for geometric pattern formation of large-scale multirobot systems.
Introduction: Geometric pattern formation is crucial in many tasks involving large-scale multi-agent systems. Examples include mobile agents performing surveillance, swarms of drones or robots, and smart transportation systems. Currently, most control strategies proposed to achieve pattern formation in network systems either show good performance but require expensive sensors and communication devices, or have lesser sensor requirements but behave more poorly. Methods and result: In this paper, we provide a distributed displacement-based control law that allows large groups of agents to achieve triangular and square lattices, with low sensor requirements and without needing communication between the agents. Also, a simple, yet powerful, adaptation law is proposed to automatically tune the control gains in order to reduce the design effort, while improving robustness and flexibility. Results: We show the validity and robustness of our approach via numerical simulations and experiments, comparing it, where possible, with other approaches from the existing literature.


Milestones in breast cancer treatment.
Modern treatment started in the 1880s with Halsted's mastectomy. The next milestone-a century later-was breast-conserving surgery, with equivalent survival but better esthetic outcomes than mastectomy. Sentinel node biopsy, introduced in the 1990s, was a milestone that permitted avoidance of axillary dissection if the sentinel node was disease-free. Chemotherapy was established for early breast cancer in the 1980s and its efficacy continues to improve; however side effects remain a concern, particularly since chemotherapy does not benefit most patients. External whole breast irradiation was introduced with conservative surgery, as it reduces recurrences. By the 2000s, 3-week regimens had been shown equivalent to standard 6-week regimens-easing pressure on patients and radiation centers. Intraoperative partial breast irradiation is potentially more beneficial as it permits complete local treatment in a single session; however, trials show that patients must be very carefully selected. From the 1990s irradiation technology was combined with imaging and computer technologies to produce equipment that directs radiation to more precisely defined target volumes, allowing increased dose to the target and markedly reduced dose to nearby tissues. Irradiation systems are evolving rapidly but are being implemented without data on long-term morbidity or efficacy, while costs rise steeply. The first targeted treatment was tamoxifen, a selective estrogen receptor inhibitor. Since its widespread use starting in the 1980s, tamoxifen has saved the lives or prolonged the survival of millions with estrogen-positive disease; it is cheap and has limited (but not negligible) side effects. The same cannot be said of newer targeted treatments like trastuzumab and pertuzumab, which, although effective against human epidermal growth factor receptor 2-positive cancer, come with important side effects and huge costs. Breast cancer mortality is declining in rich countries, but treatments have become more demanding and more expensive, so the outlook for the increasing numbers of women worldwide who develop the disease is uncertain.


Ultrasonic evaluation of trophoblastic disease and the response to chemotherapy.
Ultrasound is an established method of confirming the presence of a hydatidiform mole in utero. However, in agreement with other investigations, we have often noted that the appearance of this entity is less specific than originally reported. To elucidate this, the ultrasonic patterns of 26 patients with trophoblastic disease and 27 with other entities were reviewed. Since there is a paucity of literature with regard to the response of choriocarcinoma to chemotherapy, determined by ultrasound, we simultaneously studied the relationship between findings of the ultrasonograms and the levels of hCG-beta-subunit in sera. We noted variable ultrasonic features in trophoblastic disease, and the sonograms of the choriocarcinoma have occasionally been confused with those of hydatidiform mole. If special attention is directed to the thickness of the placenta-like echoes as well as the sonolucent areas within it, the diagnosis of partial hydatidiform mole may be feasible. We also noted a rough correlation between ultrasonic appearances and the hCG-beta-subunit value, determined during chemotherapy for choriocarcinoma.


Early enteral nutrition after total gastrectomy for gastric cancer.
To assess the difference between early enteral nutrition (EEN group) and total parenteral nutrition (TPN group) after total gastrectomy for gastric cancer. The nutrition index, liver function, patient generated subjective global assessment (PG-SGA) score, the post-operation complications, the hospital stay and hospitalization expense of the postoperative patient after total gastrectomy, admitted to our Department of Surgery from May 2011 to May 2013 were analyzed retrospectively. A total of 72 patients including 37 cases in the EEN group and 35 cases in the TPN group were recruited. Hypoalbuminemia gradually improved in the EEN group about 3-5 days, but it did not increase until average 21 days in the TPN group. The body weight decreased in the EEN group during the first 2 weeks and recovered gradually in 21 days; body weight in the TPN group was significantly lower than the EEN group at 21 days (p<0.05). There were significant differences in both the groups (p<0.05) in nutrition indicators. The incidence of complications in the EEN group and TPN group were 8.1% and 25.7% respectively, with no significant differences (p>0.05). The days of hospital stays in the EEN and in the TPN group were up to 12.2 ± 2.5 d vs 14.9 ± 2.9 d (p<0.05) and the hospitalization expenses were 36472 ± 4833 CNY vs 40140 ± 3927 CNY (p<0.05), respectively. Compared with TPN, EEN was safe and well tolerated and can shorten the hospital stay as well as reduce costs incurred with total gastrectomy for gastric cancer.


Reliability of point-of-collection testing devices for drugs of abuse in oral fluid: A systematic review and meta-analysis.
Point-of-collection testing (POCT) devices for drugs of abuse are used to screen for the presence of psychoactive substances (PAS) in different types of settings and environments. However, these quick and advantageous tools also present disadvantages, including low-reliability measures in comparison to chromatographic assays. Therefore, this article presents a systematic review and meta-analysis of studies evaluating the reliability of measurements of PAS detection in oral fluid using POCT devices. The reliability measures for detection of the five most important drug classes - cocaine, amphetamines, benzodiazepines, cannabinoids and opioids, are reported. The article also presents a subgroup analysis considering the reliability estimates for the different POCT devices that were evaluated by the studies contemplated in the review. A discussion considering the strengths and limitations of POCT techniques was performed in order to guide policymakers, traffic agents and other professionals who also conduct such tests. The use of POCT devices often involves legal and moral aspects of the subjects tested, which demands critical evaluation of these devices before they are implemented in different settings.


Parameter recovery for the rating scale model using PARSCALE.
The purpose of the present study was to investigate item and trait parameter recovery for Andrich's rating scale model using the PARSCALE computer program. The four factors upon which the simulated data matrices varied were (a) the distribution of the scale values for the items (skewed or uniform), (b) the number of category response options (4 or 5), (c) the distribution of known trait levels (normal or skewed), and (d) the sample size (60, 125, 250, 500, or 1,000). Each condition was replicated 10 times resulting in 400 data matrices. Accurate item and trait parameter estimates were obtained for all sample sizes examined. As expected, sample size seemed to have little influence on the recovery of trait parameters but did influence item parameter recovery. The distribution of known trait levels did not seriously impact the item parameter recovery. It was concluded that Andrich's rating scale model allows for the use of considerably smaller calibration samples than are typically recommended for other polytomous IRT models.


Endobronchial laser therapy.
We have sought to briefly outline the history and current role of laser therapy in airway obstruction. A primary goal in the use of laser therapy is the safe, effective, and rapid palliation of symptoms owing to tracheal or bronchial obstruction. This seems clearly supported in the literature despite some variation in definitions as to measurement of success. Objective criteria for improvement has also been studied, with authors noting improvement in walk tests, spirometric studies, and caliber of airways after treatment in significant percentages of patients. Patient survival, as noted by Ramser and Beamis, may not be the proper endpoint when discussing therapy, which for malignant causes, is meant to be palliative. Noting this, there are many benign conditions that may be effectively treated with laser therapy with a possible "cure" for some lesions defined as "carcinoma in situ." We believe laser therapy in the treatment of airway obstruction is an important tool that has proven beneficial in the therapy of benign and malignant lesions of the airway. Although future studies should prospectively examine survival characteristics, the current evidence firmly supports the use of laser as a useful modality of therapy in our endeavors to provide palliative and potentially curative care to our patients with lung disease.


[Rituximab induced remission of pemphigus vulgaris: 2 cases].
Pemphigus vulgaris frequently requires corticoids and immuno-suppressive drugs. The disease and the side effects of the drugs severely affect the quality of life, and sometime the vital prognosis of the patients. Other treatments than corticosteroids and immunosuppressive drugs are needed. We report 2 additional cases of pemphigus vulgaris uncontrolled by corticoids and immuno-suppressive drugs that responded spectacularly to rituximab. One patient had a recently onset disease, that was active despite 1,5 mg/kg/day prednisone and 1,5 g/day mycophenolate. She had a complete remission during 15 months after rituximab treatment. At relapse, another rituximab cycle led to a prompt remission. The other patient had longstanding pemphigus vulgaris complicated by cutaneous infections on prednisone (20 mg/d), immunosuppressive drugs and intravenous immune globulins. She had a prompt and complete remission after rituximab. Rituximab seems to be a promising drug for refractory pemphigus vulgaris. The benefit to risk ratio of this drug in this new indication must be precisely documented.


Increased iodine uptake by obese strain thyroid glands transplanted to normal chick embryos.
The Obese strain (OS) of chickens spontaneously develops autoimmune thyroiditis. Since a defect or abnormality of the thyroid gland may be involved in this disease experiments were performed to compare the iodine uptake of OS with normal thyroid glands. To minimize the interaction of the OS immune system with the thyroid gland during these studies, thyroids were removed from 16-day-old embryos and transferred to the chorioallantoic membrane (CAM) of 9-day-old normal White Leghorn (NWL) embryos. NWL thyroid glands were transferred to the same CAM. Six days later the 20-hr 131I uptake of the transplants was determined. Twenty OS thyroid lobes had a mean 131I uptake of 2960 +/- 740 cpm, whereas the NWL thyroids incorporated significantly less iodine (890 +/- 160 cpm; p less than 0.025). These results, along with a previous report suggest that an abnormality of the thyroid gland might be an important factor in the development of autoimmune thyroiditis.


Effects of age-related hearing loss and hearing aid experience on sentence processing.
Age-related hearing loss typically affects the hearing of high frequencies in older adults. Such hearing loss influences the processing of spoken language, including higher-level processing such as that of complex sentences. Hearing aids may alleviate some of the speech processing disadvantages associated with hearing loss. However, little is known about the relation between hearing loss, hearing aid use, and their effects on higher-level language processes. This neuroimaging (fMRI) study examined these factors by measuring the comprehension and neural processing of simple and complex spoken sentences in hard-of-hearing older adults (n = 39). Neither hearing loss severity nor hearing aid experience influenced sentence comprehension at the behavioral level. In contrast, hearing loss severity was associated with increased activity in left superior frontal areas and the left anterior insula, but only when processing specific complex sentences (i.e. object-before-subject) compared to simple sentences. Longer hearing aid experience in a sub-set of participants (n = 19) was associated with recruitment of several areas outside of the core speech processing network in the right hemisphere, including the cerebellum, the precentral gyrus, and the cingulate cortex, but only when processing complex sentences. Overall, these results indicate that brain activation for language processing is affected by hearing loss as well as subsequent hearing aid use. Crucially, they show that these effects become apparent through investigation of complex but not simple sentences.


Neurocognitive skills and vulnerability for psychosis in depression and across the psychotic spectrum: findings from the PRONIA Consortium.
Neurocognitive deficits are a core feature of psychosis and depression. Despite commonalities in cognitive alterations, it remains unclear if and how the cognitive deficits in patients at clinical high risk for psychosis (CHR) and those with recent-onset psychosis (ROP) are distinct from those seen in recent-onset depression (ROD). This study was carried out within the European project 'Personalized Prognostic Tools for Early Psychosis Management', and aimed to characterise the cognitive profiles of patients with psychosis or depression. We examined cognitive profiles for patients with ROP (n = 105), patients with ROD (n = 123), patients at CHR (n = 116) and healthy controls (n = 372) across seven sites in five European countries. Confirmatory factor analysis identified four cognitive factors independent of gender, education and site: speed of processing, attention and working memory, verbal learning and spatial learning. Patients with ROP performed worse than healthy controls in all four domains (P < 0.001), whereas performance of patients with ROD was not affected (P > 0.05). Patients at CHR performed worse than healthy controls in speed of processing (P = 0.001) and spatial learning (P = 0.003), but better than patients with ROP across all cognitive domains (all P ≤ 0.01). CHR and ROD groups did not significantly differ in any cognitive domain. These findings were independent of comorbid depressive symptoms, substance consumption and illness duration. These results show that neurocognitive abilities are affected in CHR and ROP, whereas ROD seems spared. Although our findings may support the notion that those at CHR have a specific vulnerability to psychosis, future studies investigating broader transdiagnostic risk cohorts in longitudinal designs are needed.


Probabilistic methods of identifying genes in prokaryotic genomes: connections to the HMM theory.
In this paper, we review developments in probabilistic methods of gene recognition in prokaryotic genomes with the emphasis on connections to the general theory of hidden Markov models (HMM). We show that the Bayesian method implemented in GeneMark, a frequently used gene-finding tool, can be augmented and reintroduced as a rigorous forward-backward (FB) algorithm for local posterior decoding described in the HMM theory. Another earlier developed method, prokaryotic GeneMark.hmm, uses a modification of the Viterbi algorithm for HMM with duration to identify the most likely global path through hidden functional states given the DNA sequence. GeneMark and GeneMark.hmm programs are worth using in concert for analysing prokaryotic DNA sequences that arguably do not follow any exact mathematical model. The new extension of GeneMark using the FB algorithm was implemented in the software program GeneMark.fba. Given the DNA sequence, this program determines an a posteriori probability for each nucleotide to belong to coding or non-coding region. Also, for any open reading frame (ORF), it assigns a score defined as a probabilistic measure of all paths through hidden states that traverse the ORF as a coding region. The prediction accuracy of GeneMark.fba determined in our tests was compared favourably to the accuracy of the initial (standard) GeneMark program. Comparison to the prokaryotic GeneMark.hmm has also demonstrated a certain, yet species-specific, degree of improvement in raw gene detection, ie detection of correct reading frame (and stop codon). The accuracy of exact gene prediction, which is concerned about precise prediction of gene start (which in a prokaryotic genome unambiguously defines the reading frame and stop codon, thus, the whole protein product), still remains more accurate in GeneMarkS, which uses more elaborate HMM to specifically address this task.


Swallowing and Temporomandibular Disorders in Adults.
Temporomandibular disease (TMD) etiology is multifactorial and is related to many perpetuating, predisposing, and initiating factors. The daytime parafunctions may have an important role in TMD pathogenesis. The most frequent parafunctions analyzed were the static parafunction (ie, clenching) and the dynamic parafunction (ie, grinding). In the present paper, the authors evaluated the swallowing (an oral function/parafunction) with the surface electromyography in patients with TMD. Twenty patients with TMD problems (nonhealthy patients, NHP) (mean age: 33 ± 1.994; 8 men and 12 women) and 20 healthy matched subjects (HP) (34.4 ± 2.782; 6 men and 14 women) were selected and examined. On each patient, an 8-channel surface electromyography was done during saliva swallowing. Nonhealthy patients presented higher masseter and temporalis activation (P < 0.05) and an unbalancing of temporalis and submental muscles activation (P < 0.05) than the HP. Nonhealthy patients presented a time of swallow higher than HP (P < 0.001). Nonhealthy patients presented a higher muscles activation and time of swallow than HP and a decrease of muscles balancing activation.


Efficient Propulsion and Hovering of Bubble-Driven Hollow Micromotors underneath an Air-Liquid Interface.
Bubble-driven micromotors have attracted substantial interest due to their remarkable self-motile and cargo-delivering abilities in biomedical or environmental applications. Here, we developed a hollow micromotor that experiences fast self-propulsion underneath an air-liquid interface by periodic bubble growth and collapse. The collapsing of a single microbubble induces a ∼1 m·s-1 impulsive jetting flow that instantaneously pushes the micromotor forward. Unlike previously reported micromotors propelled by the recoiling of bubbles, cavitation-induced jetting further utilizes the energy stored in the bubble to propel the micromotor and thus enhances the energy conversion efficiency by 3 orders of magnitude. Four different modes of propulsion are, for the first time, identified by quantifying the dependence of propulsion strength on microbubble size. Meanwhile, the vertical component of the jetting flow counteracts the buoyancy of the micromotor-bubble dimer and facilitates counterintuitive hovering underneath the air-liquid interface. This work not only enriches the understanding of the propulsion mechanism of bubble-driven micromotors but also gives insight into the physical aspects of cavitation bubble dynamics near the air-liquid interface on the microscale.


Association between NAFLD and risk of prevalent chronic kidney disease: why there is a difference between east and west?
There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. A total of 60,965 participants were analyzed, including 11,844 from the US and 51,229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p < 0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.


Motion Capture Depends Upon the Common Fate Factor Among Elements.
When observers move the head backwards and forwards while fixating on the center of the concentric circles that consist of oblique lines, they see illusory rotation of those circles. If several dots are superimposed on the proximity to the inner concentric circles, observers see the illusory rotation not only for the circles but also for the superimposed dots. This illusory rotation of the dots is based on motion capture. In this study, in order to understand the basis of the motion capture, we examined how motion signal with different directions (rotation, expansion/contraction, and horizontal translation) in terms of motion on a display, as well as illusory motion signal from the oblique components, affects the motion capture. If the stimulus presented rotation with expansion/contraction, or rotation with horizontal translation for the entire stimulus, then observers tended to perceive motion capture for the superimposed dots. However, if the stimulus presented only rotation of the circles, then observers tended to perceive induced motion for the superimposed dots. These results suggest that the existences of the common fate factor for the entire stimulus determine the means of allocating and integrating the motion signal in each element in the stimulus to generate motion capture.


Management for CBD stone-related mild to moderate acute cholangitis: urgent versus elective ERCP.
There is no doubt that urgent biliary decompression needs to be done in case of severe acute cholangitis. However, it remains to be determined how early biliary decompression should be performed and elective intervention would be comparable to urgent intervention, in case of mild to moderate choledocholithiasis associated cholangitis. One hundred ninety-five patients were enrolled who were diagnosed with mild to moderate cholangitis with common bile duct (CBD) stones between January 2006 and August 2010. They were divided into two groups according to door to intervention time, and urgent (≤24 h, n = 130) versus elective (>24 h, n = 82). Primary outcomes of this study were technical success rate (CBD stones removal) and clinical success rate (improvement of cholangitis) between the two groups. Hospital stay and intervention-related complications were also evaluated. There was no statistically significant difference in technical, clinical success rate and intervention-related complications between the urgent and elective groups (P = 0.737, 0.285, 0.398, respectively). Patients in the urgent group had significantly shorter hospitalization than in the elective group (6.8 vs. 9.2 days, P < 0.001), and furthermore, intervention to discharge time was also significantly shorter by 1.1 days in the urgent group (P = 0.035). In terms of laboratory parameters, initial CRP level was the only factor correlated with hospital stay and intervention to discharge time. This study demonstrates that urgent ERCP would be recommended in the management of patients with CBD stone-related mild to moderate acute cholangitis because of the advantage of short hospital stay and intervention to discharge time.


Fine motor activities in Head Start and kindergarten classrooms.
The purpose of this study was to describe and compare the fine motor activities in Head Start and kindergarten classrooms in order to open a dialogue between the two contexts about the fine motor activities children in preschool will face in kindergarten. Children in 10 Head Start and 10 kindergarten classrooms were observed for 1 day each. Time spent in activities was categorized into four groups: fine motor activities with no academic purpose, fine motor activities with academic purpose, academic activities with no fine motor component, and nonacademic activities with no fine motor component. Percentages of time were calculated and t tests were used for comparison between contexts. Children in Head Start spent 27%-46% (mean of 37%) of the in-class day in all fine motor activities whereas children in kindergarten spent 36%-66% (mean of 46%). For children in kindergarten, 42% of total fine motor activity time involved paper and pencil activities. In contrast, children in Head Start spent 10% of total fine motor activity time in paper and pencil activities. The higher mean percent of time spent in fine motor activities in kindergarten classrooms suggests a developmentally appropriate increase in fine motor demands. The percent of paper and pencil activity time the children engaged in substantially increased from Head Start to kindergarten. The findings describe a difference between the two environments, informing Head Start of the fine motor demands their graduates face in kindergarten.


Morphological changes of somatostatin neurons in the suprachiasmatic nucleus by hypophysectomy of the rat.
After hypophysectomy, behavioral circadian rhythmicities in the rat became indistinct and phase shift was observed. Therefore, it was thought that the suprachiasmatic nucleus (SCN), which is the circadian oscillator in mammals, was affected by hypophysectomy. We investigated the effects of hypophysectomy on SCN neurons using immunohistochemical staining. Wistar-Imamichi strain male rats were hypophysectomized at 60 days old. Their brains were fixed by acrolein perfusion at 10, 30 and 60 days after the operation, and then vasopressin (AVP)-, vasoactive intestinal polypeptide (VIP)- and somatostatin (SRIH)- neurons in the SCN were stained immunohistochemically. Ten days after the operation, SRIH-neurons were not found in the SCN. At 30 and 60 days after the operation, a few SRIH-positive cell bodies were recognized. In contrast, AVP- and VIP- neurons did not change in morphology in comparison with normal rats. These results suggest that hypophysectomy produces an essential change in SRIH neurons in the SCN, and that such change is responsible for the abnormal behavioral rhythms.


Effect of bait quantity and trap color on the trapping efficacy of the pheromone trap for the red palm weevil, Rhynchophorus ferrugineus.
The red palm weevil, Rhynchophorus ferrugineus (Olivier) (Curculionidae: Coleoptera), is not native to the United Arab Emirates (UAE). Since its arrival in 1985, it has been causing major damage to date palm trees. A primary control strategy has been the use of pheromone baited traps. The objectives of this study were to determine the quantity of bait, and the best trap color, to obtain the maximum catch of R. ferrugineus under field conditions in the UAE. Traps with 100, 300, or 500 g of dates as bait collected the same number of R. ferrugineus adults. Captures in black traps were significantly higher than captures in red, yellow, or white traps. Thus, using a black pheromone trap containing 100 g of dates can significantly enhance R. ferrugineus control efforts, and can help considerably in reducing the red palm weevil's deleterious impact on date palm production in UAE.


Reflective practice in medicine: The hidden curriculum challenge.
Despite the known benefits of reflection in various health care professions, it is still not a thriving practice in medical education. The literature suggests that this may be due to tensions between epistemological tenets of reflection and biomedicine. Further research is needed into experiences of doctors as they implement reflection in medical education settings. We set out to explore how these experiences were influenced by hidden curricula to provide insights into personal and contextual features of medical settings influencing engagement in reflection. Using an interpretative phenomenological analysis (IPA) approach, four semi-structured qualitative interviews were conducted virtually. Participants were doctors who graduated from a postgraduate diploma in clinical education with core reflective practice components. Interviews were recorded, transcribed, coded and analysed using IPA. Opportunities to review and amend transcriptions were provided. Three superordinate themes were identified including epistemological divergence, fear of showing vulnerability and reflection volte-face. Challenges in engaging in practices epistemologically different to predominant discourses in medicine were compounded by fears of vulnerability and a common antipathy towards reflection. All developed more accommodating perspectives towards reflection with shared experiences of a programme incorporating reflective practice. The hidden curriculum can have positive and negative impacts on doctors' engagement in reflection. In facilitating reflective practice for this group, we recommend assisting with awareness of ways of thinking and being in medicine, offering reassurance that reflection may initially feel like running contrary to predominant discourses and finally, role modelling openness to vulnerability to better integrate and promote meaningful engagement in reflection.


Prediction of a new two-dimensional valleytronic semiconductor MoGe2P4 with large valley spin splitting.
Recently, MoSi2N4 with large valley spin splitting was experimentally synthesized. However, materials with large valley spin splitting are still rare. We predict a new two-dimensional (2D) MoGe2P4 material. It has large valley spin splitting and excellent optical absorption properties. The results show that 2D MoGe2P4 is a direct semiconductor with a bandgap of 887 meV. Its valley spin splitting (ΔV) at the top of the valence band is 153 meV because of the inversion symmetry breaking and spin-orbit coupling (SOC). 2D MoGe2P4 transforms from a semiconductor to a metal under a biaxial strain of 6%. ΔV increases monotonically from 137 meV to 157 meV under biaxial strain. In addition, the lowest exciton state of 2D MoGe2P4 is near 770 nm, and the optical absorption coefficient in the ultraviolet range is higher than that of MoS2. Our results suggest that 2D MoGe2P4 has excellent potential for applications in valley electronics and optoelectronic devices.


Transcriptional responses of Arabidopsis thaliana during wilt disease caused by the soil-borne phytopathogenic bacterium, Ralstonia solanacearum.
Bacterial wilt is a common disease that causes severe yield and quality losses in many plants. In the present study, we used the model Ralstonia solanacearum-Arabidopsis thaliana pathosystem to study transcriptional changes associated with wilt disease development. Susceptible Col-5 plants and RRS1-R-containing resistant Nd-1 plants were root-inoculated with R. solanacearum strains harbouring or lacking the matching PopP2 avirulence gene. Gene expression was marginally affected in leaves during the early stages of infection. Major changes in transcript levels took place between 4 and 5 days after pathogen inoculation, at the onset of appearance of wilt symptoms. Up-regulated genes in diseased plants included ABA-, senescence- and basal resistance-associated genes. The influence of the plant genetic background on disease-associated gene expression is weak although some genes appeared to be specifically up-regulated in Nd-1 plants. Inactivation of some disease-associated genes led to alterations in the plant responses to a virulent strain of the pathogen. In contrast to other pathosystems, very little overlap in gene expression was detected between the early phases of the resistance response and the late stages of disease development. This observation may be explained by the fact that above-ground tissues were sampled for profiling whereas the bacteria were applied to root tissues. This exhaustive analysis of Arabidopsis genes whose expression is modulated during bacterial wilt development paves the way for dissecting plant networks activated by recognition of R. solanacearum effectors in susceptible plants.


Micro-CT Evaluation of Spontaneous Apexification of an Immature Tooth following Trauma.
This case reports on the micro-computerised tomography (CT) images of a periapical calcified dome following spontaneous apexification as a subsequence of trauma. An immature, maxillary central incisor was found to be non-vital one month following trauma. The tooth had minimal signs of structural damage; however, there was radiographic evidence of spontaneous apexification. The tooth suffered a second traumatic episode two years later and was decoronated to facilitate bone retention during osseous development. The patient presented with swelling and pain 36 months later, and the tooth root was extracted. The root was embedded in resin, and cross-sectional images were obtained using micro-CT. Analysis of the images provided insight into the structure of the calcified dome that formed following the first traumatic injury.


Differential fragmentation patterns of pectin oligogalacturonides observed by nanoelectrospray quadrupole ion-trap mass spectrometry using automated spectra interpretation.
Oligogalacturonides of different degrees of polymerization (DP) and methyl esterification (DE) were structurally analyzed by nanoESI quadrupole ion-trap mass spectrometry. The fragmentation patterns of the oligogalacturonides were compared using the program 'Virtual Expert Mass Spectrometrist' (VEMS) for structural annotation. In the analyzed oligogalacturonides of lower DP, the generation of C/Y ions, i.e. ions retaining the glycosidic oxygen, was higher than that of B/Z ions. In general, with oligogalacturonides of higher DP, the B/Z ions were generated more abundantly. Oligogalacturonides with free carboxylic acid groups underwent higher water loss compared to fully methyl-esterified oligogalacturonides under the same fragmentation conditions. Cross-ring cleavage, in which fragmentation occurs across the ring system of the galacturonate residue and signified by unique mass losses, was observed to be higher in fully methyl-esterified oligogalacturonides than in non-methyl-esterified ones. This study demonstrates the different fragmentation patterns of oligogalacturonides as influenced by the presence or absence of methyl ester groups. For a detailed analysis of unknown oligogalacturonides, cross-ring fragmentation gives more structural information than glycosidic bond cleavage. One implication of this is that more structural information is obtained when analyzing methyl-esterified oligogalacturonides than non-methyl-esterified ones in an ion-trap instrument. This is of particular importance in pectin chemistry, where mass spectrometry has become the technique of choice for structural determination. Although this study was not designed to explain the mechanisms of oligogalacturonide fragmentation, possible explanations for why non-methyl-esterified oligogalacturonides undergo more water loss than methyl-esterified ones will be postulated. In addition, the VEMS program was extended to automatically interpret and assign the fragment ions peaks generated in this study.


Snapshotted glass and gel transitions of stable colloidal dispersions after shear-driven aggregation in a microchannel.
Intense shear can lead to aggregation of colloids that are highly stable at rest. The aggregation process typically has an induction time, and then becomes explosive, leading to rapid phase transitions. We study the phase evolution during shear-driven aggregation in a short microchannel (MC) under intense shear for a colloid with a high interaction energy barrier that ensures high stability of particles and clusters before and after intense shear. The short residence time allows us to snapshot the phase evolution by repeatedly cycling the colloid in the MC. It is found that, depending on the particle concentration, in addition to a fluid of clusters and a solid-like gel, there is another solid-like state between them: Wigner glass of clusters. Their transitions occur over a large range of particle concentrations. We have proposed a phase diagram that describes how the transitions of the three phases evolve in the aggregation steady state in the colloidal interaction vs. particle concentration plane.


Ebola virus disease cluster in the United States--Dallas County, Texas, 2014.
Since March 10, 2014, Guinea, Liberia, and Sierra Leone have experienced the largest known Ebola virus disease (Ebola) epidemic with approximately 13,000 persons infected as of October 28, 2014. Before September 25, 2014, only four patients with Ebola had been treated in the United States; all of these patients had been diagnosed in West Africa and medically evacuated to the United States for care.


Different patterns of Akt and ERK feedback activation in response to rapamycin, active-site mTOR inhibitors and metformin in pancreatic cancer cells.
The mTOR pathway is aberrantly stimulated in many cancer cells, including pancreatic ductal adenocarcinoma (PDAC), and thus it is a potential target for therapy. However, the mTORC1/S6K axis also mediates negative feedback loops that attenuate signaling via insulin/IGF receptor and other tyrosine kinase receptors. Suppression of these feed-back loops unleashes over-activation of upstream pathways that potentially counterbalance the antiproliferative effects of mTOR inhibitors. Here, we demonstrate that treatment of PANC-1 or MiaPaCa-2 pancreatic cancer cells with either rapamycin or active-site mTOR inhibitors suppressed S6K and S6 phosphorylation induced by insulin and the GPCR agonist neurotensin. Rapamycin caused a striking increase in Akt phosphorylation at Ser(473) while the active-site inhibitors of mTOR (KU63794 and PP242) completely abrogated Akt phosphorylation at this site. Conversely, active-site inhibitors of mTOR cause a marked increase in ERK activation whereas rapamycin did not have any stimulatory effect on ERK activation. The results imply that first and second generation of mTOR inhibitors promote over-activation of different pro-oncogenic pathways in PDAC cells, suggesting that suppression of feed-back loops should be a major consideration in the use of these inhibitors for PDAC therapy. In contrast, metformin abolished mTORC1 activation without over-stimulating Akt phosphorylation on Ser(473) and prevented mitogen-stimulated ERK activation in PDAC cells. Metformin induced a more pronounced inhibition of proliferation than either KU63794 or rapamycin while, the active-site mTOR inhibitor was more effective than rapamycin. Thus, the effects of metformin on Akt and ERK activation are strikingly different from allosteric or active-site mTOR inhibitors in PDAC cells, though all these agents potently inhibited the mTORC1/S6K axis.


Enhancing cardiovascular risk prediction through AI-enabled calcium-omics.
Coronary artery calcium (CAC) is a powerful predictor of major adverse cardiovascular events (MACE). Traditional Agatston score simply sums the calcium, albeit in a non-linear way, leaving room for improved calcification assessments that will more fully capture the extent of disease. To determine if AI methods using detailed calcification features (i.e., calcium-omics) can improve MACE prediction. We investigated additional features of calcification including assessment of mass, volume, density, spatial distribution, territory, etc. We used a Cox model with elastic-net regularization on 2457 CT calcium score (CTCS) enriched for MACE events obtained from a large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). We employed sampling techniques to enhance model training. We also investigated Cox models with selected features to identify explainable high-risk characteristics. Our proposed calcium-omics model with modified synthetic down sampling and up sampling gave C-index (80.5%/71.6%) and two-year AUC (82.4%/74.8%) for (80:20, training/testing), respectively (sampling was applied to the training set only). Results compared favorably to Agatston which gave C-index (71.3%/70.3%) and AUC (71.8%/68.8%), respectively. Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were important determinants of increased risk, with dense calcification (>1000HU) associated with lower risk. The calcium-omics model reclassified 63% of MACE patients to the high risk group in a held-out test. The categorical net-reclassification index was NRI=0.153. AI analysis of coronary calcification can lead to improved results as compared to Agatston scoring. Our findings suggest the utility of calcium-omics in improved prediction of risk.


Poor performance status, urban residence and female sex predict inferior survival in pediatric advanced stage mature B-NHL in an Indian tertiary care center.
Advanced stage is a known prognostic factor in B-Non-Hodgkin Lymphoma (NHL); however, factors within advanced stage and overall data on pediatric B-NHL from India are lacking. This is a retrospective study wherein all consecutive pediatric (≤18 years) patients of advanced stage B-NHL (St. Jude stage 3 and 4) treated at our center from Jan 2003 to June 2016 with BFM-90 protocol were evaluated for outcome and pathology review. Total 140 patients were analyzed with median age 8 years; M:F ratio was 5.2:1; 36% patients presented within 30 days of symptom onset and 58% had rural residence. Burkitt lymphoma (66%) was commonest histopathological subtype; bone marrow was involved in 15% and CSF in 8% cases. Undernourishment was observed in 30% patients and 51% had ECOG performance status of 3&4. At 5 years, EFS was 52 ± 4% (CI 0.43-0.60) and OS was 61 ± 4% (CI 0.52-0.68). On multivariate analysis, poor performance status (p < 0.001) and urban residence (p = 0.016) emerged as significant negative prognostic factors for EFS; while for OS, female sex (p = 0.006), poor performance status (p < 0.001) and urban residence (p = 0.023) predicted inferior outcome. This is the largest study from south Asia on advanced stage pediatric B-NHL and it suggests undernourishment, poor performance status and gender bias to be unique features at presentation. Although, outcomes are comparable with other data from resource-challenged nations, yet they are 15-20% inferior than trial data from other developed countries. Further, poor performance status, female sex and urban residence for poor outcome were identified as unique prognostic factors.


Use of the International Classification for Nursing Practice in the construction of a care protocol.
to describe the use of the International Classification for Nursing Practice (ICNP®) in the construction of a nursing care protocol for children undergoing hematopoietic stem cell transplantation. experience report. nursing problems were defined based on complications identified in a previous study; later, the ICNP® enabled the organization and systematization of childcare. The care protocol consists of 40 nursing problems, with their human needs affected, diagnoses and nursing interventions. The axes Focus, Judgment, Location, Action, Means, Time, and Client were used in the elaboration of diagnoses and interventions proposed in the protocol. Final Considerations: the use of the classification allowed the establishment of nursing interventions compatible with the needs of the child undergoing transplantation, providing support for the care protocol. It made it possible to encourage the use of classification in this context, contribute to patient safety and strengthen professional practice.


Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions.
Embryo morphogenesis is impacted by dynamic changes in tissue material properties, which have been proposed to occur via processes akin to phase transitions (PTs). Here, we show that rigidity percolation provides a simple and robust theoretical framework to predict material/structural PTs of embryonic tissues from local cell connectivity. By using percolation theory, combined with directly monitoring dynamic changes in tissue rheology and cell contact mechanics, we demonstrate that the zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively predict and experimentally verify hallmarks of PTs, including power-law exponents and associated discontinuities of macroscopic observables. Finally, we show that this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions causing random and, consequently, uniform changes in cell connectivity. Collectively, our theoretical and experimental findings reveal the structural basis of material PTs in an organismal context.


Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause.
The protection afforded by postmenopausal oestrogen replacement against cardiovascular disease is not fully explained by changes in plasma lipoproteins. To investigate the effect of oestrogen on arterial tone, Doppler ultrasound was used to assess blood flow characteristics in the internal carotid arteries of 12 postmenopausal women. Patients were studied pretreatment and at weeks 4, 6, 9, and 22 of therapy with transdermal oestradiol 50 micrograms/day. The pulsatility index (PI), which is thought to represent impedance to blood flow distal to the point of sampling, was measured from the flow velocity waveform. 11 of the 12 patients were within 5 years of menopause; 1 was 8 years postmenopausal but had experienced bleeding 4 years after menopause. In the 11 women there was a highly significant correlation (r = 0.77) between time since menopause and baseline PI. A similar correlation (r = 0.74) was observed when the episode of postmenopausal bleeding was redefined as time of menopause in the twelfth patient. For all 12 patients, there was a significant negative correlation (r = -0.70) between change in PI during transdermal oestradiol therapy and mean of baseline plus week 22 PI value. For all correlations between changes in PI and time since menopause, the longer the time the greater the fall in PI. These results, and previous observations of a reduction in uterine artery PI with oestradiol treatment, suggest that oestrogen has a generalised effect on the arterial system.


Near-infrared reflectance spectroscopy for predicting amino acids content in intact processed animal proteins.
Near-infrared calibrations were developed for the instantaneous prediction of amino acids composition of processed animal proteins (PAPs). Two sample presentation modes were compared (ground vs intact) for demonstrating the viability of the analysis in the intact form, avoiding the need for milling. Modified partial least-squares (MPLS) equations for the prediction of amino acids in PAPs were developed using the same set of samples (N = 92 PAPs) analyzed in ground and intact form and in three cups differing in the optical window size. The standard error for cross validation (SECV) and the coefficient of determination (1-VR) values yielded with the calibrations developed using the samples analyzed in the intact form showed similar or even better accuracy than those obtained with finely ground samples. The excellent predictive ability (1-VR > 0.90; CV < 3.0%) obtained for the prediction of amino acids in intact processed animal proteins opens an enormous expectative for the on-line implementation of NIRS technology in the processing and marketing of these important protein feed ingredients, alleviating the costs and time associated with the routine quality controls.


Communication between spaces formed by fasciae of male external genitalia and perineum: computed tomographic cadaveric study and clinical significance.
The purposes were to evaluate the communication and the extent of the spaces formed by fasciae of the male external genitalia and the perineum and to correlate the spaces with clinical observations regarding anatomic progression of diseases. Multi-detector row computed tomography (CT) was performed through the perineum and the pelvis of 5 fresh cadavers injected with contrast material in the space between dartos and Buck fasciae of the penis. Two of the 5 cadavers, injected with the contrast material mixed with blue ink, were dissected to confirm the observations made on multi-detector row computed tomography. Computed tomographic images of 11 patients with diseases involving the potential spaces formed by the fasciae of the male genitalia and the perineum were correlated with observations made on CT of the cadavers. The contrast material filling the scrotal cavity extended posteriorly in the perineum, remained far below the urogenital diaphragm, and reached superiorly to the potential space along Scarpa fascia in all cadavers. At cadaveric dissection, the ink-stained spaces were confined by the fascial planes involving Colles, Buck, dartos, and Scarpa fasciae. Spread of disease in the 11 patients (6 patients with localized genital edema, 4 with Fournier gangrene, and 1 with bulbous urethral rupture) was confined in the spaces demonstrated on CT images of the cadavers. Free communication and disease spread occur within the confines of the superficial perineal, scrotal, penile, and abdominal wall spaces formed by Colles, Buck, dartos, and Scarpa fasciae.


Metabolic complications of HIV and AIDs.
Numerous anecdotal reports, clinical observations, and newly published studies provide evidence of the growing interest and concern about body shape changes and metabolic complications seen in HIV infection. At first believed to be a single complication caused by the protease inhibitor class of antiretroviral therapy, the focus of research is shifting to distinct syndromes with multiple causes. In this unfolding story, peripheral fat atrophy, central fat accumulation, dyslipidemia, and glucose disregulation characterize the more commonly recognized syndromes. Osteoporosis and osteopenia have been recently observed. While the etiologies await discovery, the long-term consequences of these metabolic changes demand the expertise of clinicians not formerly considered "front-line" in HIV/AIDS treatment, such as orthopaedic nurses.


Quantum thermal diode based on two interacting spinlike systems under different excitations.
We demonstrate that two interacting spinlike systems characterized by different excitation frequencies and coupled to a thermal bath each, can be used as a quantum thermal diode capable of efficiently rectifying the heat current. This is done by deriving analytical expressions for both the heat current and rectification factor of the diode, based on the solution of a master equation for the density matrix. Higher rectification factors are obtained for lower heat currents, whose magnitude takes their maximum values for a given interaction coupling proportional to the temperature of the hotter thermal bath. It is shown that the rectification ability of the diode increases with the excitation frequencies difference, which drives the asymmetry of the heat current, when the temperatures of the thermal baths are inverted. Furthermore, explicit conditions for the optimization of the rectification factor and heat current are explicitly found.


Seismic cycles, size of the largest events, and the avalanche size distribution in a model of seismicity.
We address several questions on the behavior of a numerical model recently introduced to study seismic phenomena, which includes relaxation in the plates as a key ingredient. First, we make an analysis of the scaling of the largest events with system size and show that, when parameters are appropriately interpreted, the typical size of the largest events scale as the system size, without the necessity to tune any parameter. Second, we show that the temporal activity in the model is inherently nonstationary and obtain from here justification and support for the concept of a "seismic cycle" in the temporal evolution of seismic activity. Finally, we ask for the reasons that make the model display a realistic value of the decaying exponent b in the Gutenberg-Richter law for the avalanche size distribution. We explain why relaxation induces a systematic increase in b from its value b≃0.4 observed in the absence of relaxation. However, we have not been able to justify the actual robustness of the model in displaying a consistent b value around the experimentally observed value b≃1.


A dose-finding trial with a novel ingenol derivative (ingenol disoxate: LEO 43204) for field treatment of actinic keratosis on full face or 250 cm2 on the chest.
Actinic keratoses (AKs) may progress to squamous cell carcinoma and can occur in cancerized fields as sub-clinical and clinically visible lesions. Ingenol disoxate gel is a topical field therapy for AK. This Phase I/II trial aimed to assess the safety and efficacy of ingenol disoxate on full face or chest in patients with AKs. Part 1 was a phase-I, open-label, dose-escalation trial investigating the maximum tolerated dose of ingenol disoxate. Part 2 was a phase-II, randomized, double-blind, vehicle-controlled trial; patients were randomized 1:1:1:1 to ingenol disoxate 0.018%, 0.012%, 0.006% gel or vehicle for 2 consecutive days. Reduction in AK count from baseline at Week 8 was significantly higher than with vehicle for all doses of ingenol disoxate gel (0.018%, 79.0%; 0.012%, 73.4%; 0.006%, 69.7%; vehicle; 42.3%; p < .001). Local skin responses peaked at Day 3 for all doses, rapidly declined, and reached mild levels at Week 2. Most adverse events were mild or moderate in intensity, and were most commonly application site pain/pruritus. Ingenol disoxate gel is efficacious and well tolerated as field treatment for AKs on the full face or chest. Clinical Trial No.: NCT01922050.


Self-organized graphene nanosheets with corrugated, ordered tip structures for high-performance flexible field emission.
Patterned reduced graphene oxide (rGO) films with vertically aligned tip structures are fabricated by a straightforward self-assembly method. The size, uniformity of the patterns, and alignment of the tips are successfully controlled according to the concentration of a GO/octadecylamine (ODA)-dispersed solution. The surface energy difference between the GO/ODA solution and a self-assembled water droplet is a critical parameter for determining the pattern structure. Numerous rGO nanosheets are formed so as to be vertically aligned with respect to the substrate during film fabrication at GO concentrations below 2.0 g/L. These samples provide high field-emission characteristics. The patterned rGO arrays are highly flexible with preservation of the field emission properties, even at large bending angles. This is attributed to the high crystallinity, emitter density, and good chemical stability of the rGO arrays, as well as the strong interactions between the rGO arrays and the substrate.


Fission yeast Dss1 associates with the proteasome and is required for efficient ubiquitin-dependent proteolysis.
Human DSS1 associates with BRCA2, a tumour suppressor protein required for efficient recombinational DNA repair, but the biochemical function of DSS1 is not known. Orthologues of DSS1 are found in organisms such as budding yeast and fission yeast that do not have BRCA2-related proteins, indicating that DSS1 has a physiological role independent of BRCA2. The DSS1 orthologue in Saccharomyces cerevisiae has been shown to associate with the 26 S proteasome and, in the present paper, we report that in the distantly related fission yeast Schizosaccharomyces pombe, Dss1 associates with the 19 S RP (regulatory particle) of the 26 S proteasome. A role for S. pombe Dss1 in proteasome function is supported by three lines of evidence. First, overexpression of two components of the 19 S RP, namely Pad1/Rpn11 and Mts3/Rpn12, rescued the temperature-sensitive growth defect of the dss1 mutant. Secondly, the dss1 mutant showed phenotypes indicative of a defect in proteasome function: growth of the dss1 mutant was inhibited by low concentrations of L-canavanine, an amino acid analogue, and cells of the dss1 mutant accumulated high molecular mass poly-ubiquitylated proteins. Thirdly, synthetic growth defects were found when the dss1 mutation was combined with mutations in other proteasome subunit genes. These findings show that DSS1 has an evolutionarily conserved role as a regulator of proteasome function and suggest that DSS1 may provide a link between BRCA2 and ubiquitin-mediated proteolysis in human cells.


Technical aspects of laparoscopic ovarian autograft in ewes after cryopreservation by slow-cooling protocol.
Iatrogenic ovarian failure and infertility are long term-term side effects of anticancerous gonadotoxic treatments in children or women of reproductive year. Ovarian cortex cryopreservation can be a solution to preserve immature germinal cells before gonadotoxic treatment, for later transplantation. The aim of our study was to prove the efficiency of a laparoscopic technique for orthotopic graft after a slow-freezing/thawing protocol, and to evaluate the effect of ovarian cryopreservation and autograft on the primordial follicle survival rate. Experimental surgical study was performed on 6- to 12-month-old ewes. The study was approved by the ethic committee of the Lyon-veterinary-school. The left ovary was removed by laparoscopy and cut in half, and medulla was excised. In group 1 (n = 6), autograft was performed immediately on the right ovary, and in group 2 (n = 6), graft was performed after a slow-freezing/thawing protocol. The second hemi-ovary served as an ungrafted control fragment. A polypropylene/polyglactin mesh was included between graft and base to separate the two structures, to help histological analysis. The mean graft performance time was 71 +/- 8 min in the first group and 57 +/- 10 min in the second. Freezing did not affect the number of primordial follicles. In the ungraft control fragments, the global anomaly rate (cytoplasm plus nuclear anomaly) increased after freezing (p < 0.05). Others results did not reach signification. Pelvic adhesion occurred only once. The post-graft primordial follicle survival rate was 5.1 +/- 2.8% in the non-frozen group vs. 6.3 +/- 2.3% after freezing/thawing. Kruskal-Wallis and Wilkoxon non-parametric tests were used for statistical analysis. Laparoscopy seems to be a well-adapted technique for ovarian tissue orthotopic autograft. The main follicle loss occurs before graft revascularization. Our orthotopic graft's procedure has to be improved to obtain a better graft's neovascularization, and to have a better long-term post-graft primordial follicle survival rate.


Asymptomatic Urolithiasis Complicated by Nephrocutaneous Fistula.
Asymptomatic spontaneous nephrocutaneous fistula is a rare and severe complication of chronic urolithiasis. We report a case of 56-year-old woman with a nephrocutaneous fistula (NFC) which developed from a superinfected urinoma following calyceal rupture due to an obstructing calculus in the left ureter. The patient was clinically asymptomatic and came to the emergency department for a painless left flank fluctuating mass. This urinoma was superinfected, with a delayed development of renal abscesses and perirenal phlegmon found on contrast-enhanced uro-computed tomography (CT), responsible for left renal vein thrombophlebitis and left psoas abscess. Thereafter, a 99 mTc dimercaptosuccinic acid (DMSA) scintigraphy revealed a nonfunctional left kidney, leading to the decision of left nephrectomy. Chronic urolithiasis complications are rare and only few cases are reported in medical literature. A systematic medical approach helped selecting the best imaging modality to help diagnosis and treatment. Indeed, uro-CT scan and renal scintigraphy with 99 mTc-DMSA are the most sensitive imaging modalities to investigate morphological and functional urinary tract consequences of NFC, secondary to chronic urolithiasis.


No response to hepatitis B vaccine in infants born to HBsAg(+) mothers is associated to the transplacental transfer of HBsAg.
No or low hepatitis B (HB) vaccine response is more frequent in infants from HBsAg(+) mothers than those from HBsAg(-). Our previous study found temporary positivity of HBsAg in infants from HBsAg(+) mothers. In this study, we hypothesized that HBsAg in infant blunt immune response to standard hepatitis B vaccination. A total of 328 consecutive HBsAg(+) mothers and their offspring were enrolled. Blood samples were taken from mothers and their infants and quantified for HBsAg, anti-HBs titer and HBV DNA load concentration; Placenta samples were collected to stain for HBsAg. First, 6.7% infants (22/328) showed anti-HBs titer lower than 10 mIU/mL after HB vaccination (non-response to HB vaccine). HBsAg(+) newborns showed higher risk of non-response than HBsAg(-) infants (13.0% versus 5.0%, p = 0.016). Infants from high HBsAg titer mothers displayed higher risk of HBsAg positivity at birth than those from low titer mothers (45.3% versus 2.8%, p < 0.001). HBsAg titer in mothers of HBsAg(+) newborns was much higher than mothers of HBsAg(-) newborns (p < 0.001). All those data supported HBsAg can be transferred through placenta. Our hypothesis was further reinforced by immunostaining with specific antibody against HBsAg, a substantial higher prevalence (87.5% versus 30.8%, p = 0.024) and stronger immunostaining (p = 0.008) was demonstrated in HBsAg(+) group comparing with placenta of the HBsAg(-) group. No response to HB vaccine in infants of HBsAg(+) mothers was associated to the transplacental transfer of HBsAg.


S100A8/A9 Drives Neuroinflammatory Priming and Protects against Anxiety-like Behavior after Sepsis.
Sepsis commonly results in acute and chronic brain dysfunction, which dramatically increases the morbidity associated with this common disease. Chronic brain dysfunction in animal models of sepsis survival is linked to persistent neuroinflammation and expression of multiple cytokines. However, we have found previously that microglia predominantly upregulate the damage associated molecule S100A8/A9 after sepsis. In this article, we show that S100A8/A9 is increased in the brains of patients who died of sepsis and that S100A8 is expressed in astrocytes and myeloid cells. Using a mouse model of sepsis survival, we show that S100A8/A9 is persistently expressed in the brain after sepsis. S100A9 expression is necessary for recruitment of neutrophils to the brain and for priming production of reactive oxygen species and TNF-α secretion in microglia and macrophages. However, despite improving these indices of chronic inflammation, S100A9 deficiency results in worsened anxiety-like behavior 2 wk after sepsis. Taken together, these results indicate that S100A8/A9 contributes to several facets of neuroinflammation in sepsis survivor mice, including granulocyte recruitment and priming of microglial-reactive oxygen species and cytokine production, and that these processes may be protective against anxiety behavior in sepsis survivors.


Mitochondrial function and redox control in the aging eye: role of MsrA and other repair systems in cataract and macular degenerations.
Oxidative stress occurs when the level of prooxidants exceeds the level of antioxidants in cells resulting in oxidation of cellular components and consequent loss of cellular function. Oxidative stress is implicated in wide range of age-related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself. In the anterior segment of the eye, oxidative stress has been linked to lens cataract and glaucoma while in the posterior segment of the eye oxidative stress has been associated with macular degeneration. Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O(2)(-)) production. Superoxide production precedes subsequent reactions that form potentially more dangerous reactive oxygen species (ROS) species such as the hydroxyl radical (OH), hydrogen peroxide (H(2)O(2)) and peroxynitrite (OONO(-)). The major source of ROS in the mitochondria, and in the cell overall, is leakage of electrons from complexes I and III of the electron transport chain. It is estimated that 0.2-2% of oxygen taken up by cells is converted to ROS, through mitochondrial superoxide generation, by the mitochondria. Generation of superoxide at complexes I and III has been shown to occur at both the matrix side of the inner mitochondrial membrane and the cytosolic side of the membrane. While exogenous sources of ROS such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins may contribute to the oxidative milieu, mitochondria are perhaps the most significant contribution to ROS production affecting the aging process. In addition to producing ROS, mitochondria are also a target for ROS which in turn reduces mitochondrial efficiency and leads to the generation of more ROS in a vicious self-destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Fig. 1). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr) protein repair system and other redox systems play key roles in the function and maintenance of the aging eye.


Single payers and multiple lists: must everyone get the same coverage in a universal health plan?
In spite of recent political setbacks for the movement toward universal health insurance, considerable support remains for the idea. Among those supporting such plans, most assume that a universal insurance system, especially if it is a single-payer system, would offer a single list of basic covered services. This paper challenges that assumption and argues for the availability of multiple lists of services in a universal insurance system. The claim is made that multiple lists will be both more efficient and more fair. Any single list will fund some services that are quite attractive to some people, but only marginally attractive to others. Thus any single-list plan will fund some services that produce only marginal benefit for the resources used. Moreover, since some people will hold values quite compatible with the single list and others will hold values leading to preferences for unfunded services, some people will get much more benefit from any single list than other people will. Fairness and efficiency require providing an entitlement to universal access to health insurance that could be purchased by typical consumers for a fixed price of perhaps $3500. By permitting everyone to pick their preferred list of services available at that price, each person will efficiently use his or her entitlement while getting more equal opportunity for benefits.


Skin colour and vitamin D: An update.
Homo sapiens evolved in East Africa and had dark skin, hair, and eyes, in order to protect against deleterious consequences of intensive UV radiation at equatorial latitudes. Intensive skin pigmentation was thought to bear the risk of inefficient vitamin D3 synthesis in the skin. This initiated the hypothesis that within the past 75 000 years, in which humans migrated to higher latitudes in Asia and Europe, the need for vitamin D3 synthesis served as an evolutionary driver for skin lightening. In this review, we summarize the recent archeogenomic reconstruction of population admixture in Europe and demonstrate that skin lightening happened as late as 5000 years ago through immigration of lighter pigmented populations from western Anatolia and the Russian steppe but not primarily via evolutionary pressure for vitamin D3 synthesis. We show that variations in genes encoding for proteins being responsible for the transport, metabolism and signalling of vitamin D provide alternative mechanisms of adaptation to a life in northern latitudes without suffering from consequences of vitamin D deficiency. This includes hypotheses explaining differences in the vitamin D status and response index of European populations.


Participant protection with the use of records: ethical issues and recommendations.
This article explores the ethical concerns and protections that may be required when individually identifiable data originally collected solely for clinical or administrative purposes are used in research or evaluation. It asks the following broad question with respect to the interim policy developed by the Substance Abuse and Mental Health Services Administration (SAMHSA) to protect the rights and welfare of participants in its programs: For those programs and projects not classified as research, are the protections and system for review adequate? Background information on SAMHSA's interim policy is provided, along with issues and questions related to the use of clinical and administrative records in research and evaluation. The article concludes with recommendations for modifying the existing participant protection guidelines, based on the preceding discussion of issues and questions.


Complete Desorption of Hybrid Nanoclays Composed of Hydrotalcite and Disperse Dye.
Clays are considered great nanoadsorbents for many materials, including textile dyes. The use of these materials for cleaning textile wastewater is well known; however, it is not at all common to find applications for the hybrid materials formed from the clay and dye. In this work, a dye-loaded clay material was used to make new dye baths and colour a polyester textile substrate. The same hybrid could be used several times as it did not use all the adsorbed dye in a single dyeing. The hybrid obtained from hydrotalcite (nanoclay) and the dispersed red 1 dye was analysed by measuring the colour obtained, carrying out an X-ray diffraction analysis that provided information after each desorption-dyeing process, and using infrared spectroscopy to analyse the specific bands of each characteristic group. Both analyses showed that the amount of dye present in the hybrid decreases. Thermogravimetry (TGA), surface area and porosity measurements (BET), and X-ray photoelectron spectroscopy (XPS) tests were conducted. Chemical stability was assessed by subjecting the hybrid to the actions of different reagents. In addition, colour fastness tests were carried out after dyeing and washing the polyester test tubes to check for the correct fixing of the dye to the fibre. These fastness results showed that the dyeing was carried out correctly and as if it was a conventional dyeing process.