Synergistic effect of garcinol and curcumin on antiproliferative and apoptotic activity in pancreatic cancer cells.
Pancreatic cancer (PaCa) is a major health concern due to its aggressiveness and early metastasis. Current treatments for PaCa are limited by development of resistance against therapy. As an alternative strategy, we assessed the combinatorial effect of dietary compounds, garcinol and curcumin, on human PaCa cells (BxPC-3 and Panc-1). A significant (P < 0.05) dose-dependent reduction in cell viability and increase in apoptosis were observed in both cell lines as compared to untreated controls. A combination index (CI) value < 1, for a two-way comparison of curcumin and garcinol, suggests synergism. The potency (Dm) of the combination of garcinol and curcumin was 2 to 10 fold that of the individual agents. This indicates that curcumin and garcinol in combination exhibit a high level of synergism, with enhanced bioactivity, thereby reducing the required effective dose required for each individually. This combinatorial strategy may hold promise in future development of therapies against PaCa.


Replication and Refinement of an Algorithm for Automated Drusen Segmentation on Optical Coherence Tomography.
Here, we investigate the extent to which re-implementing a previously published algorithm for OCT-based drusen quantification permits replicating the reported accuracy on an independent dataset. We refined that algorithm so that its accuracy is increased. Following a systematic literature search, an algorithm was selected based on its reported excellent results. Several steps were added to improve its accuracy. The replicated and refined algorithms were evaluated on an independent dataset with the same metrics as in the original publication. Accuracy of the refined algorithm (overlap ratio 36-52%) was significantly greater than the replicated one (overlap ratio 25-39%). In particular, separation of the retinal pigment epithelium and the ellipsoid zone could be improved by the refinement. However, accuracy was still lower than reported previously on different data (overlap ratio 67-76%). This is the first replication study of an algorithm for OCT image analysis. Its results indicate that current standards for algorithm validation do not provide a reliable estimate of algorithm performance on images that differ with respect to patient selection and image quality. In order to contribute to an improved reproducibility in this field, we publish both our replication and the refinement, as well as an exemplary dataset.


Treatment of climacteric complaints with oestriol.
150 women with serious climacteric complaints were continuously treated from January, 1970, up to April, 1972, with Ovestin¿, an orally effective preparation containing 1 mg of oestriol per tablet. After one month of treatment subjective complaints were already considerably improved. Oestrogenic activity was markedly increased, according to vaginal smears and total gonadotrophin excretion in the urine. Its high tolerance and beneficial therapeutic effect make Ovestin the preparation of choice in the treatment of the climacteric syndrome.


Dynamic cerebral autoregulation during and after handgrip exercise in humans.
The purpose of the present study was to examine the effect of static exercise on dynamic cerebral autoregulation (CA). In nine healthy subjects at rest before, during, and after static handgrip exercise at 30% maximum voluntary contraction, the response to an acute drop in mean arterial blood pressure and middle cerebral artery mean blood velocity was examined. Acute hypotension was induced nonpharmacologically via rapid release of bilateral thigh occlusion cuffs. Subjects were instructed to avoid executing a Valsalva maneuver during handgrip. To quantify dynamic CA, the rate of regulation (RoR) was calculated from the change in cerebral vascular conductance index during the transient fall in blood pressure. There was no significant difference in RoR between rest (mean+/-SE; 0.278+/-0.052/s), exercise (0.333+/-0.053/s), and recovery (0.305+/-0.059/s) conditions (P=0.747). In addition, there was no significant difference in the rate of absolute cerebral vasodilatory response to acute hypotension between three conditions (P=0.737). This finding indicates that static exercise and related elevations in blood pressure do not alter dynamic CA.


CD1d-mediated lipid presentation by CD11c+ cells regulates intestinal homeostasis.
Intestinal homeostasis relies on a continuous dialogue between the commensal bacteria and the immune system. Natural killer T (NKT) cells, which recognize CD1d-restricted microbial lipids and self-lipids, contribute to the regulation of mucosal immunity, yet the mechanisms underlying their functions remain poorly understood. Here, we demonstrate that NKT cells respond to intestinal lipids and CD11c+ cells (including dendritic cells (DCs) and macrophages) are essential to mediate lipid presentation within the gut ultimately controlling intestinal NKT cell homeostasis and activation. Conversely, CD1d and NKT cells participate in the control of the intestinal bacteria composition and compartmentalization, in the regulation of the IgA repertoire and in the induction of regulatory T cells within the gut. These changes in intestinal homeostasis require CD1d expression on DC/macrophage populations as mice with conditional deletion of CD1d on CD11c+ cells exhibit dysbiosis and altered immune homeostasis. These results unveil the importance of CD11c+ cells in controlling lipid-dependent immunity in the intestinal compartment and reveal an NKT cell-DC crosstalk as a key mechanism for the regulation of gut homeostasis.


Homeostasis and Defense at the Surface of the Eye. The Conjunctival Microbiota.
The literature on ocular microbiome has grown tremendously over the past decade, and our knowledge of the different aspects and roles in homeostasis and protection is continuously growing. The development of 16 S rRNA sequencing has allowed the field to characterize communities of bacteria in health and ocular disease. Efforts should continue to further elucidate the interplay between microbiome and key players, such as age, comorbidities, and contact lens usage in order to have better control of the sight-threatening complications.


The antihypertensive efficacy of verapamil in the elderly evaluated by ambulatory blood pressure measurement.
To assess the efficacy, tolerability and pharmacokinetics of verapamil in the elderly, ten patients with blood pressure greater than 160/90 mmHg were studied in a randomized double-blind placebo-controlled cross-over trial. Nine patients aged 75 (+/- 4.9) years completed the study. After titration, doses of verapamil varying from 40 to 120 mg (40 mg in four, 80 mg in one and 120 mg in four patients) twice daily for six weeks were taken. Mean (+/- SEM) clinic lying blood pressure was reduced on verapamil from 187 +/- 6.8/100 +/- 4.1 to 167 +/- 4.6/86 +/- 3.1 mmHg, [P less than 0.001). Mean ambulatory blood pressure was reduced from 174 +/- 1.4/95 +/- 1.0 to 169 +/- 1.3/90 +/- 0.8 mmHg, (P less than 0.01). Lying heart rate was significantly reduced but glomerular filtration rate, renal blood flow and mental function, were not altered by treatment. The mean plasma half-life of verapamil was 6.9 +/- 1.1 hours. Side effects were minimal. We conclude that verapamil is an effective blood pressure lowering agent in the elderly.


Human autoantibodies that react with both cell nuclei and plasma membranes display specificity for the octamer of histones H2A, H2B, H3, and H4 in high salt.
Sera of some patients with systemic lupus erythematosus and related diseases contain a polyclonal antibody population (cross-reactive antinuclear antibodies [X-ANA]) that react specifically with both core mononucleosomes and plasma membranes of viable nucleated cells. Native mononucleosomes and nucleosome cores assembled from long DNA and the inner histones were indistinguishable in terms of inhibition of binding of X-ANA to nuclei of tissue sections and to polynucleosomes on the walls of plastic tubes. In contrast, mononucleosomes selectively depleted of histones H2A and H2B did not inhibit these reactions. A method was developed for isolation of X-ANA from serum that took advantage of the dual specificity of these antibodies. Immunosedimentation in sucrose density gradients revealed that 125I-labeled Fab' fragments of highly pure X-ANA formed complexes with the inner histones H2A, H2B, H3, and H4 in 2 M NaCL, but not in 0.15 M salt. These results indicate that X-ANA recognize an epitope of the inner histone in 2 M salt, and that in 0.15 M NaCL this epitope is not formed unless the histones interact with DNA to generate a nucleosome structure. Furthermore, in light of the previous demonstration that the epitope is destroyed by trypsin, it may be localized in the N-terminal region of histone H2A or H2B.


[Maternal mortality in the Huichol area of Jalisco state, Mexico. The Study Group on Maternal Mortality].
With the aim of estimating the level of maternal mortality, a field survey in 349 Huichol families was carried out from August 1990 to August 1991, using an ad-hoc questionnaire. In 208 deliveries, five maternal deaths were recorded, rendering a maternal mortality rate of 2,403.8 per 100,000 live births. This is a considerably higher rate than those reported at the state and national levels, as well as in other municipalities of the region. All five deaths were due to direct maternal causes and took place during the puerperium. None of the patients received medical care. The high maternal mortality rate observed among Huichol groups can be explained by their disadvantageous social conditions, their lack of access to health care, and also their cultural patterns which, in turn, determine their reproductive behaviour. All these elements place Huichol groups among the worst served populations in Mexico.


Mimosa-inspired design of a flexible pressure sensor with touch sensitivity.
A bio-inspired flexible pressure sensor is generated with high sensitivity (50.17 kPa(-1)), quick responding time (<20 ms), and durable stability (negligible loading-unloading signal changes over 10 000 cycles). Notably, the key resource of surface microstructures upon sensor substrates results from the direct molding of natural mimosa leaves, presenting a simple, environment-friendly and easy scale-up fabrication process for these flexible pressure sensors.


Metal-Free Regiodivergent Addition of Carbon Nucleophiles to α,β-Unsaturated Electrophiles.
A mild and metal-free regiodivergent addition of carbon nucleophiles to α,β-unsaturated electrophiles was developed. Total 1,2-regioselectivity was observed in the addition of nitrobenzyl chloride derivative 1 to α,β-unsaturated aldehydes 2 in the presence of TDAE. Moreover, the reaction between p-nitrobenzyl chloride 1a and α,β-unsaturated iminium salts 4 led to the formation of the 1,4-adduct with total regioselectivity.


Lattice Boltzmann modeling of self-propelled Leidenfrost droplets on ratchet surfaces.
In this paper, the self-propelled motion of Leidenfrost droplets on ratchet surfaces is numerically investigated using a thermal multiphase lattice Boltzmann model with liquid-vapor phase change. The capability of the model for simulating evaporation is validated via the D(2) law. Using the model, we first study the performances of Leidenfrost droplets on horizontal ratchet surfaces. It is numerically shown that the motion of self-propelled Leidenfrost droplets on ratchet surfaces is owing to the asymmetry of the ratchets and the vapor flows beneath the droplets. It is found that the Leidenfrost droplets move in the direction toward the slowly inclined side from the ratchet peaks, which agrees with the direction of droplet motion in experiments [Linke et al., Phys. Rev. Lett., 2006, 96, 154502]. Moreover, the influences of the ratchet aspect ratio are investigated. For the considered ratchet surfaces, a critical value of the ratchet aspect ratio is approximately found, which corresponds to the maximum droplet moving velocity. Furthermore, the processes that the Leidenfrost droplets climb uphill on inclined ratchet surfaces are also studied. Numerical results show that the maximum inclination angle at which a Leidenfrost droplet can still climb uphill successfully is affected by the initial radius of the droplet.


Unexpectedly high bacteriochlorophyll a concentrations in neotropical tank bromeliads.
The contribution of bacteriochlorophyll a (BChl a) to photosynthetically driven electron transport is generally low in aquatic and terrestrial systems. Here, we provide evidence that anoxygenic bacterial phototrophy is widespread and substantial in water retained by tank bromeliads of a primary rainforest in French Guiana. An analysis of the water extracted from 104 randomly selected tank bromeliads using infrared fluorimetry suggested the overall presence of abundant anoxygenic phototrophic bacterial populations. We found that purple bacteria dominated these populations responsible for unusually high BChl a/chlorophyll a ratios (>50%). Our data suggest that BChl a-based phototrophy in tank bromeliads can have significant effects on the ecology of tank-bromeliad ecosystems and on the carbon and energy fluxes in Neotropical forests.


Clinical value of ST-segment change after return of spontaneous cardiac arrest and emergent coronary angiography in patients with out-of-hospital cardiac arrest: Diagnostic and therapeutic importance of vasospastic angina.
We investigated the association between initial ST-segment change after return of spontaneous circulation (ROSC) and the incidence of acute coronary lesions in patients with out-of-hospital cardiac arrest (OHCA), and clinical outcomes of patients with OHCA caused by vasospastic angina pectoris (VSA). Among 2779 OHCA patients in our institution, all patients with ROSC underwent emergent coronary angiography (CAG) except for those with an obvious extra-cardiac cause of OHCA. Initial ST-segment changes after ROSC were reviewed, and 30-day survival and neurological outcome (Cerebral Performance Category) were evaluated. Of the 155 patients, 52 (34%) had ST-segment elevation (STE) and 103 (66%) had non-STE. Significant coronary culprit lesions were present in 81% of patients with STE and in 33% of patients with non-STE ( P<.001). Percutaneous coronary intervention (PCI) was successful in 60 patients (93.8%) and failed in 4 patients (6.2%). Among 155 patients, 74 patients (47.7%) had favorable neurological prognosis, and 104 patients (67.1%) were alive at 30 days. ST-segment analysis showed good positive predictive value (81%) but low negative predictive value (68%) in diagnosing the presence of acute coronary lesions. VSA was found in 5 patients (9.6%) in the STE group and in 12 patients (11.7%) in the non-STE group. Of these 17 patients, 9 (52.9%) had favorable neurological outcome and 14 (82.4%) were alive at 30 days. An acute culprit lesion may be the cause of OHCA even in the absence of STE. In survivors of OHCA with normal coronary arteries, spasm provocation testing should be performed to detect VSA as a cause of the arrest.


Isolation and characterization of a gene coding for chitin deacetylase specifically expressed during fruiting body development in the basidiomycete Flammulina velutipes and its expression in the yeast Pichia pastoris.
Fv-pda, a gene coding for chitin deacetylase (CDA), was isolated from the basidiomycete Flammulina velutipes by differential display targeted for genes specifically expressed during fruiting body development. The fv-pda ORF comprises 250 amino acid residues and is interrupted by 10 introns. The fv-pda cDNA was expressed in the yeast Pichia pastoris, and the resulting recombinant FV-PDA was used for enzymatic characterization. The recombinant FV-PDA catalyses deacetylation of N-acetyl-chitooligomers, from dimer to pentamer, glycol chitin and colloidal chitin. The fv-pda was specifically expressed through the entire stage of fruiting body development, and the transcript was abundant in stipes of mature fruiting bodies. These results suggest that CDA plays an important role in the process of fruiting of F. velutipes.


[Comparative study of intraocular pressure measurements by Goldmann applanation tonometer, noncontact tonometer and TonoPen].
The purpose of the study was to compare the levels of the intraocular pressure (NOT) measured in one eye at the same moment by three different methods: by Goldmann applanation tonometer (AT), non-contact tonometer (BT) and Tono-Pen (TP). It was further set the average variability of the performed measurements for particular tonometric methods. NOT was assessed in 106 eyes of 106 subjects aged 7-77 years (average 34.3 +/- 17.1 years). NOT was measured at the same moment with BT, TP and AT. The obtained data were statistically analyzed. The average NOT was 16.55 +/- 2.95, 17.95 +/- 4.47 and 16.13 +/- 3.4 mmHg when AT, BT and TP were applied. Average variability of three measurements for AT, BT and TP was 1.51 +/- 0.96, 1.78 +/- 1.08 and 1.47 +/- 0.9 mmHg. Average NOT levels of the measured AT and TP were almost identical with a difference of 0.42 mmHg (p = 0.236). Average level of the intraocular pressure measured by BT was higher by 1.40 mmHg and 1.82 mmHg in comparison with AT and TP (p = 0.00002), respectively. NOT measurement produced almost identical average levels at AT and TP, whereas at BT the levels were much higher. Average variability of the three subsequent NOT measurements was the highest at BT, whereas at AT and TP the average variability was lower and nearly identical.


Carbon Fibers Embedded With Iron Selenide (Fe 3 Se 4 ) as Anode for High-Performance Sodium and Potassium Ion Batteries.
The development of sodium and potassium ion batteries (SIBs/KIBs) has seen tremendous growth in recent years due to their promising properties as a potential replacement for lithium-ion batteries (LIBs). Here, we report ultrafine iron selenide (Fe3Se4) nanoparticles embedded into one-dimensional (1D) carbon fibers (Fe3Se4@CFs) as a potential candidate for SIBs/KIBs. The Fe-based metal-organic framework particles (MOFP) are used as a Fe source to obtain highly dispersed Fe3Se4 nanoparticles in the product. The Fe3Se4@CF consisted of ultrafine particles of Fe3Se4 with an average particle size of ~10 nm loaded into CFs with an average diameter of 300 nm. The product exhibited excellent specific activity of ~439 and ~435 mAh/g at the current density of 50 mA/g for SIBs and KIBs, respectively. In addition, the as-prepared anodes (Fe3Se4@CFs) exhibited excellent capacity retention up to several hundred cycles (700 cycles for SIBs and 300 cycles for KIBs). The high activity and excellent stability of the developed electrodes make Fe3Se4@CFs a promising electrode for next-generation batteries.


Detection of IgG, IgA, IgM and IgE antibodies in invasive amoebiasis in endemic areas.
Entamoeba histolytica-specific serum IgG, IgA, IgM and IgE antibodies were assayed in cases of amoebiasis in an endemic area. Patient groups consisted of amoebic liver abscess (n = 18), preabscess hepatic amoebiasis (n = 22) and amoebic colitis (n = 30). Control subjects comprised 26 asymptomatic cyst passers, 13 giardiasis cases, 20 typhoid patients and 24 non-amoebic individuals. Serum IgG was assayed by ELISA, using a monoclonal anti IgG beta-galactosidase (IgG beta-gal) conjugate, a polyclonal avidin biotin horse radish peroxidase (AB-HRP), and a polyclonal anti IgG horse radish peroxidase (IgG HRP) conjugate. IgA and IgM were assayed by the beta-gal ELISA and IgE by AB-HRP. Diagnostically significant IgG and IgA while lower IgM and IgE antibody levels were seen in extraintestinal cases. About 40% of suspected pre-abscess hepatic amoebiasis cases were confirmed by antibody estimation. All isotype levels in most dysentery cases were in the range of the controls.


Robust and Elastic Polymer Membranes with Tunable Properties for Gas Separation.
Polymer membranes with the capability to process a massive volume of gas are especially attractive for practical applications of gas separation. Although much effort has been devoted to develop novel polymer membranes with increased selectivity, the overall gas-separation performance and lifetime of membrane are still negatively affected by the weak mechanical performance, low plasticization resistance and poor physical aging tolerance. Recently, elastic polymer membranes with tunable mechanical properties have been attracting significant attentions due to their tremendous potential applications. Herein, we report a series of urethane-rich PDMS-based polymer networks (U-PDMS-NW) with improved mechanical performance for gas separation. The cross-link density of U-PDMS-NWs is tailored by varying the molecular weight (Mn) of PDMS. The U-PDMS-NWs show up to 400% elongation and tunable Young's modulus (1.3-122.2 MPa), ultimate tensile strength (1.1-14.3 MPa), and toughness (0.7-24.9 MJ/m3). All of the U-PDMS-NWs exhibit salient gas-separation performance with excellent thermal resistance and aging tolerance, high gas permeability (>100 Barrer), and tunable gas selectivity (up to α[PCO2/PN2] ≈ 41 and α[PCO2/PCH4] ≈ 16). With well-controlled mechanical properties and gas-separation performance, these U-PDMS-NW can be used as a polymer-membrane platform not only for gas separation but also for other applications such as microfluidic channels and stretchable electronic devices.


Identification of bile acid and fatty acid species as candidate rapidly bactericidal agents for topical treatment of gonorrhoea.
Novel therapeutic strategies are urgently needed for Neisseria gonorrhoeae, given its increasing antimicrobial resistance. Treatment of oropharyngeal N. gonorrhoeae infections has proven particularly challenging, with most reported treatment failures of the first-line drug ceftriaxone occurring at this site and lower cure rates in recent trials of new antibiotics reported for oropharyngeal infections compared with other sites of infection. However, the accessibility of the oropharynx to topical therapeutics provides an opportunity for intervention. Local delivery of a therapeutic at a high concentration would enable the use of non-traditional antimicrobial candidates, including biological molecules that exploit underlying chemical sensitivities of N. gonorrhoeae but lack the potency or pharmacokinetic profiles required for effective systemic administration. Two classes of molecules that are thought to limit gonococcal viability in vivo, bile acids and short- and medium-chain fatty acids, were examined for rapid bactericidal activity. The bile acids deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA), but not other bile acid species, exerted extremely rapid bactericidal properties against N. gonorrhoeae, reducing viability more than 100 000-fold after 1 min. The short-chain fatty acids formic acid and hexanoic acid shared this rapid bactericidal activity. All four molecules are effective against a phylogenetically diverse panel of N. gonorrhoeae strains, including clinical isolates with upregulated efflux pumps and resistance alleles to the most widely used classes of existing antimicrobials. DCA and CDCA are both approved therapeutics for non-infectious indications and are well-tolerated by cultured epithelial cells. DCA and CDCA are attractive candidates for further development as anti-gonococcal agents.


Magnetic cellulose-TiO2 nanocomposite microspheres for highly selective enrichment of phosphopeptides.
Novel magnetic cellulose-TiO2 nanocomposite microspheres with high surface areas and magnetic susceptibility were fabricated, which exhibited remarkably selective enrichment of trace phosphopeptides from peptide mixtures.


Exploring the potential of open big data from ticketing websites to characterize travel patterns within the Chinese high-speed rail system.
Big data have contributed to deepen our understanding in regards to many human systems, particularly human mobility patterns and the structure and functioning of transportation systems. Resonating the recent call for 'open big data,' big data from various sources on a range of scales have become increasingly accessible to the public. However, open big data relevant to travelers within public transit tools remain scarce, hindering any further in-depth study on human mobility patterns. Here, we explore ticketing-website derived data that are publically available but have been largely neglected. We demonstrate the power, potential and limitations of this open big data, using the Chinese high-speed rail (HSR) system as an example. Using an application programming interface, we automatically collected the data on the remaining tickets (RTD) for scheduled trains at the last second before departure in order to retrieve information on unused transit capacity, occupancy rate of trains, and passenger flux at stations. We show that this information is highly useful in characterizing the spatiotemporal patterns of traveling behaviors on the Chinese HSR, such as weekend traveling behavior, imbalanced commuting behavior, and station functionality. Our work facilitates the understanding of human traveling patterns along the Chinese HSR, and the functionality of the largest HSR system in the world. We expect our work to attract attention regarding this unique open big data source for the study of analogous transportation systems.


Variety in bone marrow 18F-FDG uptake in Hodgkin lymphoma patients without lymphomatous bone marrow involvement: does it have an explanation?
To directly correlate fluorine-18 fluoro-2-deoxy-D-glucose (F-FDG) uptake of the iliac crest, as determined with PET, with both spatially matched histological bone marrow parameters and laboratory markers in Hodgkin lymphoma patients without lymphomatous bone marrow involvement at bone marrow biopsy. This retrospective study included 21 patients with newly diagnosed Hodgkin lymphoma who underwent F-FDG-PET and who had a lymphoma-negative bone marrow biopsy of the right posterior iliac crest. F-FDG-PET maximum standardized uptake value (SUVmax) was measured in the right posterior iliac crest and correlated to histological bone marrow parameters (cellularity, myeloid/erythroid ratio, degree of fibrosis, and reactive T- and B-lymphocytes) and laboratory markers (hemoglobin, C-reactive protein lactate dehydrogenase, and leukocyte and thrombocyte counts) using Pearson's correlation coefficient (R) for Gaussian data or Kendall's tau (τ) for non-Gaussian data. There was a significant moderate correlation between F-FDG-PET SUVmax and cellularity of the iliac crest (R=0.519, P=0.016). Furthermore, there was a significant strong inverse correlation between F-FDG-PET SUVmax of the iliac crest and hemoglobin level (R=-0.661, P=0.001) and there was a significant moderate correlation between F-FDG-PET SUVmax of the iliac crest and C-reactive protein level (τ=0.441, P=0.007). All other correlations, including F-FDG-PET SUVmax of the right iliac crest versus reactive T- and B-lymphocytes in the bone marrow, were not significant. The observations suggest increased bone marrow F-FDG uptake to be caused by red marrow hyperplasia because of anemia in Hodgkin lymphoma. Increased bone marrow F-FDG uptake is unlikely to be caused by inflammatory bone marrow changes.


[Hearing loss due to chemotherapy and radiation therapy in young children].
Modern treatment of pediatric cancer patients has improved survival and life expectancy. However, treatment is associated with significant side-effects, including hearing loss. Hearing impairment has an important impact on language, communication and social skills, as well as on academic performance in school. 1. Characterize hearing loss caused by treatment of pediatric cancer. 2. Define the impact of hearing loss on language development. 3. Describe techniques for intervention. A retrospective review of ten children averaging five years of age who were referred to MICHA, a center specializing in treating hearing impaired children. For each child, at least four hearing tests were obtained, various language acquisition tests administered and methods of interventions recorded. All the subjects had high-tone symmetric sensorineural hearing loss; at 4000 Hz it reached 80 dB HL. Low frequency tones were better preserved. Pure-tone thresholds were worse than speech reception thresholds. Hearing aids improved hearing thresholds. Nine out of the ten children experienced a delay in language acquisition. The treatment plan included: hearing aids, hearing training, intervention in language and communication skills, emotional support and preparation for elementary school. Hearing loss amongst pediatric cancer patients as a consequence of treatment is extremely common. Delays in acquisition of language skills are seen in the majority of these children. Pediatric cancer patients should be referred to a proper diagnostic and intervention program. They are likely to benefit from monitoring the hearing before, during and after treatment, and from interventions to improve their hearing, language and communication skills. In addition, audiometry and otoacoustic emissions should be used to identify early damage to the inner ear. Noise and further exposure to ototoxic medications should be avoided.


Second-line intra-arterial chemotherapy in advanced pancreatic adenocarcinoma.
The present study was conducted to evaluate activity and toxicity of the FLEC (folinic acid 100 mg/m2; 5-fluorouracil 1000 mg/m2; carboplatin 300 mg/m2; epirubicin 60 mg/m2) schedule as second-line treatment for progressive locally advanced or metastatic pancreatic cancer (LAMPC). FLEC was administered every 3 weeks with an angiographic catheter introduced into the tumor vascular bed. Thirty-two patients were enrolled. Twenty patients had a PS of 2. Twenty-five patients had metastatic disease to liver. Seven (21.9%) partial responses were observed (WHO criteria). Fifteen patients (46.9%) had stable disease and ten patients (31.2%) had progressive disease. The median OS from the diagnosis was 11.8 months. PS (p=0.0308) and pain (WHO scale, p=0.0222; analogic scale, p=0.0446) significantly improved after therapy. No patient discontinued treatment because of toxicity (NCI-CTC criteria). The current study shows that intraarterial chemotherapy is a good therapeutic option in second-line treatment of LAMPC.


Risk and Protective Factors for the Use of Illicit Drugs: Perspective of the Users.
This article aimed to describe the perspective of people who make harmful use of illicit substances on the contributions of risk and protective factors to the development of problems related to drug use. One hundred eleven participants were recruited from a health service for drug users in a city in the interior of the state of São Paulo through posters with information, distribution of brochures, and snowball sampling technique. The sample consists of 51.9% men and 48.1% women, with 81.3% single and 10.3% married. Among them, 54.2% of participants completed high school, 64.1% were Catholic, and 34% rarely practiced their religion. The results on risk factors were classified into three domains, namely, "personal characteristics and behaviors," "family circumstances," and "other social pressures," and those on protective factors were also classified into three domains, namely, "personal characteristics and behaviors," "family circumstances," and "circumstances in the community." The data make it possible to guide the incorporation of multiple strategies to protect the consumption of illicit drugs in human biopsychosocial development, especially among children and adolescents.


Facebook Recruitment of Vaccine-Hesitant Canadian Parents: Cross-Sectional Study.
There is concern over the increase in the number of "vaccine-hesitant" parents, which contributes to under-vaccinated populations and reduced herd immunity. Traditional studies investigating parental immunization beliefs and practices have relied on random digit dialing (RDD); however, this method presents increasing limitations. Facebook is the most used social media platform in Canada and presents an opportunity to recruit vaccine-hesitant parents in a novel manner. The study aimed to explore the use of Facebook as a tool to reach vaccine-hesitant parents, as compared with RDD methods. We recruited Canadian parents over 4 weeks in 2013-14 via targeted Facebook advertisements linked to a Web-based survey. We compared methodological parameters, key parental demographics, and three vaccine hesitancy indicators to an RDD sample of Canadian parents. Two raters categorized respondent reasons for difficulties in deciding to vaccinate, according to the model of determinants of vaccine hesitancy developed by the World Health Organization's Strategic Advisory Group of Experts on Immunization. The Facebook campaign received a total of 4792 clicks from unique users, of whom 1696 started the Web-based survey. The total response rate of fully completed unique Web-based surveys was 22.89% (1097/4792) and the survey completion rate was 64.68% (1097/1696). The total cost including incentives was reasonable (Can $4861.19). The Web-based sample yielded younger parents, with 85.69% (940/1097) under the age of 40 years as compared with 23.38% (408/1745) in the RDD sample; 91.43% (1003/1097) of the Facebook respondents were female as compared with 59.26% (1034/1745) in the RDD sample. Facebook respondents had a lower median age of their youngest child (1 year vs 8 years for RDD). When compared with the RDD sample, the Web-based sample yielded a significantly higher proportion of respondents reporting vaccines as moderately safe to not safe (26.62% [292/1097] vs 18.57% [324/1745]), partially or not at all up-to-date vaccination status of youngest child (22.06% [242/1097] vs 9.57% [167/1745]), and difficulty in making the decision to vaccinate their youngest child (21.06% [231/1097] vs 10.09% [176/1745]). Out of the Web-based respondents who reported reasons for the difficulties in deciding to vaccinate, 37.2% (83/223) reported lack of knowledge or trust due to conflicting information and 23.8% (53/223) reported the perception of the risk of the adverse effects of vaccines being higher than the risk of disease acquisition. We successfully recruited a large sample of our target population at low cost and achieved a high survey completion rate using Facebook. When compared with the RDD sampling strategy, we reached more vaccine-hesitant parents and younger parents with younger children-a population more likely to be making decisions on childhood immunizations. Facebook is a promising economical modality for reaching vaccine-hesitant parents for studies on the determinants of vaccine uptake.


Non-rigid registration and non-local principle component analysis to improve electron microscopy spectrum images.
Image registration and non-local Poisson principal component analysis (PCA) denoising improve the quality of characteristic x-ray (EDS) spectrum imaging of Ca-stabilized Nd2/3TiO3 acquired at atomic resolution in a scanning transmission electron microscope. Image registration based on the simultaneously acquired high angle annular dark field image significantly outperforms acquisition with a long pixel dwell time or drift correction using a reference image. Non-local Poisson PCA denoising reduces noise more strongly than conventional weighted PCA while preserving atomic structure more faithfully. The reliability of and optimal internal parameters for non-local Poisson PCA denoising of EDS spectrum images is assessed using tests on phantom data.


Comparison of Ramosetron with Palonosetron for Prevention of Postoperative Nausea and Vomiting in Patients Receiving Opioid-Based Intravenous Patient-Controlled Analgesia after Gynecological Laparoscopy.
We aimed to compare the effects of ramosetron and palonosetron in the prevention of postoperative nausea and vomiting (PONV) in patients that received opioid-based intravenous patient-controlled analgesia (IV-PCA) after gynecological laparoscopy. We reviewed the electronic medical records of 755 adults. Patients were classified into two groups, ramosetron (group R, n = 589) versus palonosetron (group P, n = 166). Based on their confounding factors, 152 subjects in each group were selected after the implementation of propensity score matching. The overall incidence of PONV at postoperative day (POD) 0 was lower in group R compared to group P (26.9% versus 36.8%; P = 0.043). The severity of nausea was lower in group R than in group P on postoperative day (POD) 0 (P = 0.012). Also, the complete responder proportion of patients was significantly higher in group R compared to that in group P on POD 0 (P = 0.043). In conclusion, ramosetron showed a greater efficacy in the prevention of postoperative nausea at POD 0 compared to palonosetron in patients after gynecological laparoscopy.


Child and youth participation in sexual health-related discussions, decisions, and actions in Njombe, Tanzania: A focused ethnography.
Sexual health is a signficant dimension of health among children and youth in Tanzania. Local discourses highlight concerns regarding HIV/AIDS and sexual violence. The aim of this study was to examine the experiences and participation of children and youth in sexual health-related discussions, decisions, and actions in Njombe; a Tanzanian rural community. A focused ethnography, with a participatory approach, was conducted over a 3.5 month period, using participant observation, group interviews, and analysis of key texts, as well as key informant advisors. Twenty-eight participants, 8-16 years of age, were recruited from a community Youth Peer Health Educator program and an HIV youth group. Four principal themes were identified: (a) knowledge and understanding of sexual health, (b) children/youth value sexual health education and discussion, (c) supports and barriers for participation in sexual health education, and (d) children/youth value participation in their own care and promotion of their health. Results demonstrated that these children/youth have the capacities, interests, and values to actively participate in matters affecting their health and sexual health. Specific barriers and supports to sexual health education were identified. The study demonstrated how young people's agency is socially mediated and can persist even when confronting significant barriers.


Ustiloxins, fungal cyclic peptides, are ribosomally synthesized in Ustilaginoidea virens.
Ustiloxins A and B are toxic cyclic tetrapeptides, Tyr-Val/Ala-Ile-Gly (Y-V/A-I-G), that were originally identified from Ustilaginoidea virens, a pathogenic fungus affecting rice plants. Contrary to our report that ustiloxin B is ribosomally synthesized in Aspergillus flavus, a recent report suggested that ustiloxins are synthesized by a non-ribosomal peptide synthetase in U.virens. Thus, we analyzed the U.virens genome, to identify the responsible gene cluster. The biosynthetic gene cluster was identified from the genome of U.virens based on homologies to the ribosomal peptide biosynthetic gene cluster for ustiloxin B identified from A.flavus. It contains a gene encoding precursor protein having five Tyr-Val-Ile-Gly and three Tyr-Ala-Ile-Gly motifs for ustiloxins A and B, respectively, strongly indicating that ustiloxins A and B from U.virens are ribosomally synthesized. Accession codes of the U.virens and A.flavus gene clusters in NCBI are BR001221 and BR001206, respectively. Supplementary data are available at Bioinformatics online.


A proposed classification of veterinary epidemiosurveillance networks.
With the signing of the General Agreement on Tariffs and Trade and the establishment of the World Trade Organisation, the trading environment for animal products has changed. Disease control measures can no longer be applied as trade barriers unless supported by scientific epidemiological data. In this context, it has become necessary, if not obligatory, to gain accurate and up-to-date knowledge about the epidemiological status of important infectious animal diseases. The role of veterinary epidemiosurveillance networks is therefore gaining importance. Furthermore, epidemiosurveillance contributes to the protection of animal populations from exotic or emerging diseases, as well as to the development and evaluation of disease control programmes. Despite the large diversity of surveillance networks, the authors propose a method of network classification. The criteria for classification are as follows: the type of disease being monitored (i.e., surveillance of exotic versus endemic diseases). The number of diseases concerned (i.e., focused networks versus broad-based networks). The area being covered (i.e., local, national or international networks). The population being monitored (i.e., whether the network is targeted at suspect or susceptible animals). The sampling strategy of the network (i.e., sample-based networks versus exhaustive networks). The method of collecting data (i.e., passive data collection versus active collection). The type of network management (i.e., autonomous management versus that which is integrated with other programmes). This classification is discussed and illustrated by examples published in the literature. It may aid in the future development of a grid for the evaluation of veterinary epidemiosurveillance networks.


A universal assay for screening expression libraries for carbohydrases.
Although many assays are available for the screening of expression libraries for carbohydrases, some enzymes cannot be detected because their substrates are incompatible with the existing assays. One thing that all carbohydrases have in common is that they increase the number of reducing ends when degrading their substrates. In this paper we explore the possibility of detecting this increase with the highly sensitive bicinchoninic acid (BCA) reducing value assay. This assay can be used for the detection of all carbohydrases degrading any polysaccharide; enzymes with either an exo- or an endo-type of mechanism can be detected at the same time. A cDNA library of Aspergillus tubigensis expressed in Kluyveromyces lactis clones, was screened with this assay for the presence of xylogalacturonan degrading enzyme(s). High background absorbances caused by culture medium, by proteins produced by the clones and by substrate could be dealt with by using the precautions described in this note. Three xylogalacturonase producing clones were found using this procedure.


Formation of mercapturic acids in rats after the administration of aralkyl esters.
1. Benzylmercapturic acid and hippuric acid were isolated from the urine of rats that had been injected subcutaneously with benzyl acetate. 2. 1-Menaphthylmercapturic acid and 1-naphthoic acid were isolated from the urine of rats after the subcutaneous injection of each of the following compounds: 1-menaphthyl alcohol and its acetate, propionate, butyrate and benzoate esters. 3. A quantitative method for determining 1-menaphthylmercapturic acid in urine was developed and used to measure the excretion of this compound in the urine of rats in the 4-day period after the subcutaneous injection of 1-menaphthyl alcohol and its acetate, propionate, butyrate and benzoate esters. 4. Chromatographic evidence was obtained for the presence of S-(1-menaphthyl)glutathione and S-(1-menaphthyl)-l-cysteine in bile collected from rats with cannulated bile ducts after the animals had been injected subcutaneously with each of the following compounds: S-(1-menaphthyl)glutathione, 1-menaphthyl acetate, propionate and butyrate. 5. Benzylmercapturic acid and 1-menaphthylmercapturic acid were isolated from the urine of rats that had been injected with sodium benzyl sulphate and sodium 1-menaphthyl sulphate respectively.


Forecasting model for Pea seed-borne mosaic virus epidemics in field pea crops in a Mediterranean-type environment.
An empirical model was developed to forecast Pea seed-borne mosaic virus (PSbMV) incidence at a critical phase of the annual growing season to predict yield loss in field pea crops sown under Mediterranean-type conditions. The model uses pre-growing season rainfall to calculate an index of aphid abundance in early-August which, in combination with PSbMV infection level in seed sown, is used to forecast virus crop incidence. Using predicted PSbMV crop incidence in early-August and day of sowing, PSbMV transmission from harvested seed was also predicted, albeit less accurately. The model was developed so it provides forecasts before sowing to allow sufficient time to implement control recommendations, such as having representative seed samples tested for PSbMV transmission rate to seedlings, obtaining seed with minimal PSbMV infection or of a PSbMV-resistant cultivar, and implementation of cultural management strategies. The model provides a disease forecast risk indication, taking into account predicted percentage yield loss to PSbMV infection and economic factors involved in field pea production. This disease risk forecast delivers location-specific recommendations regarding PSbMV management to end-users. These recommendations will be delivered directly to end-users via SMS alerts with links to web support that provide information on PSbMV management options. This modelling and decision support system approach would likely be suitable for use in other world regions where field pea is grown in similar Mediterranean-type environments.


Robust high-throughput prokaryote de novo assembly and improvement pipeline for Illumina data.
The rapidly reducing cost of bacterial genome sequencing has lead to its routine use in large-scale microbial analysis. Though mapping approaches can be used to find differences relative to the reference, many bacteria are subject to constant evolutionary pressures resulting in events such as the loss and gain of mobile genetic elements, horizontal gene transfer through recombination and genomic rearrangements. De novo assembly is the reconstruction of the underlying genome sequence, an essential step to understanding bacterial genome diversity. Here we present a high-throughput bacterial assembly and improvement pipeline that has been used to generate nearly 20 000 annotated draft genome assemblies in public databases. We demonstrate its performance on a public data set of 9404 genomes. We find all the genes used in multi-locus sequence typing schema present in 99.6 % of assembled genomes. When tested on low-, neutral- and high-GC organisms, more than 94 % of genes were present and completely intact. The pipeline has been proven to be scalable and robust with a wide variety of datasets without requiring human intervention. All of the software is available on GitHub under the GNU GPL open source license.


Vegetarian Dietary Patterns and Cognitive Function among Older Adults: The Adventist Health Study-2.
We explored effects on cognitive function of following plant-based vegetarian compared with non-vegetarian dietary patterns in otherwise healthy older community-dwelling members of the Adventist Health Study-2 cohort (n = 132). Cognition was assessed using a comprehensive neuropsychological battery; a principal components analysis derived processing speed, executive function, and memory/language factors. Mild memory impairment (MMI) (n = 26, 19.7%) was identified by memory tests. Vegetarians consumed (a) meats, fish, and dairy <1 time/month, (b) dairy ≥1 time/month and meats, and fish <1 time/month, or (c) fish ≥1 time/month, no limits on dairy, and meats <1 time/month. Dietary patterns were determined at baseline, for each decade, and at cognitive assessment; a diet stability score was calculated. Factor scores were not different between vegetarians and non-vegetarians, nor was dietary pattern associated with a lower odds of MMI. A more stable diet over the life course was associated with better memory/language [β = 0.021 SE(β) = 0.008; p = 0.01]. This exploratory study did not support differences in processing speed, executive function, or memory/language abilities between vegetarians and non-vegetarians but did suggest that a more stable dietary pattern which was characteristic of vegetarians was associated with better memory/language abilities.


[Silicosis, chronic bronchitis and smoking habits].
In 333 patients suffereing from silicosis the incidence of chronic bronchitis and/or obstruction of the respiratory tract has been correlated with cigarette smoking. The incidence of chronic bronchitis and/or airway obstruction in patients who had acquired either slight or severe silicosis in Switzerland was over 50%. A positive correlation between cigarette smoking and chronic bronchitis and/or airway obstruction could be found only in younger patients with slight silicosis. Chronic bronchitis and/or airway obstruction was not more frequent in foundry-workers suffering from silicosis where they had been exposed to fumes which irritated the respiratory tract. Deformation of the respiratory tract due to silicosis has a greater bearing on the development of chronic bronchitis and airway obstruction than immoderate cigarette smoking.


Media portrayal of nurses' perspectives and concerns in the SARS crisis in Toronto.
To describe nursing work life issues as portrayed in the media during the SARS crisis in Toronto. Content analysis of local and national news media documents in Canada. Media articles were sorted and classified by topic, and themes were identified. Themes were: (a) changing schemas of nursing practice: the new normal; (b) barriers to relational nursing work; (c) work life concerns: retention and recruitment; (d) nursing virtue: nurses as heroes and professionals; (e) paradoxical responses to nurses from the community; and (f) leadership in nursing during the SARS crisis. This analysis enhanced understanding of how nurses are portrayed in the media, but it indicated the significance of quality of work life and issues about work-home life. Some descriptions of the care and caring of nurses have made nursing seem like an important and influential profession to potential applicants who might previously have dismissed nursing as a career.


ICD-10 coding algorithms for defining comorbidities of acute myocardial infarction.
With the introduction of ICD-10 throughout Canada, it is important to ensure that Acute Myocardial Infarction (AMI) comorbidities employed in risk adjustment methods remain valid and robust. Therefore, we developed ICD-10 coding algorithms for nine AMI comorbidities, examined the validity of the ICD-10 and ICD-9 coding algorithms in detection of these comorbidities, and assessed their performance in predicting mortality. The nine comorbidities that we examined were shock, diabetes with complications, congestive heart failure, cancer, cerebrovascular disease, pulmonary edema, acute renal failure, chronic renal failure, and cardiac dysrhythmias. Coders generated a comprehensive list of ICD-10 codes corresponding to each AMI comorbidity. Physicians independently reviewed and determined the clinical relevance of each item on the list. To ensure that the newly developed ICD-10 coding algorithms were valid in recording comorbidities, medical charts were reviewed. After assessing ICD-10 algorithms' validity, both ICD-10 and ICD-9 algorithms were applied to a Canadian provincial hospital discharge database to predict in-hospital, 30-day, and 1-year mortality. Compared to chart review data as a 'criterion standard', ICD-9 and ICD-10 data had similar sensitivities (ranging from 7.1-100%), and specificities (above 93.6%) for each of the nine AMI comorbidities studied. The frequencies for the comorbidities were similar between ICD-9 and ICD-10 coding algorithms for 49,861 AMI patients in a Canadian province during 1994-2004. The C-statistics for predicting 30-day and 1 year mortality were the same for ICD-9 (0.82) and for ICD-10 data (0.81). The ICD-10 coding algorithms developed in this study to define AMI comorbidities performed similarly as past ICD-9 coding algorithms in detecting conditions and risk-adjustment in our sample. However, the ICD-10 coding algorithms should be further validated in external databases.


Double-Versus Single-Bundle Anterior Cruciate Ligament Reconstructive Surgery: A Prospective Study With >1 Year Follow-Up.
Background The increased prevalence of knee trauma predominantly adds to the anterior cruciate ligament (ACL) tear frequencies that require single- or double-bundle reconstructive surgeries. Few studies have demonstrated the superior results of double-bundle reconstruction compared to single-bundle approaches. This study investigated the knee function improvement capacity of both reconstruction techniques in patients with ACL tears. Methods Thirty cases with ACL tears have been enrolled and segregated equally in distinct (single-bundle versus double-bundle) batches. The diagnostic assessments were undertaken through comprehensive clinical history, knee radiographs, Lysholm scoring, the International Knee Documentation Committee (IKDC) scale, the Lachman analysis, the International Knee Documentation Committee (IKDC) scale, and the pivot shift method. Results After one year, there was a significant enhancement in the postoperative versus preoperative Lysholm scores in the single-bundle (58.5 ± 21.2 vs. 82.4 ± 26.2, p<0.001) and double-bundle (86.4 ± 22.8 vs 60.3 ± 19.2, p<0.001) groups. There was a significant improvement in the IKDC scores after a follow-up period of one year (p-value: 0.012 and p-value: 0.002, respectively) in both of the study batches. After a year of follow-up, Lysholm scores (p=0.352) and IKDC scores (p=0.574) between the study groups (82.4 ± 26.2 vs. 86.4 ± 22.8) were comparable. Conclusion The clinical outcomes remained comparable between subjects with single-bundle reconstruction versus double-bundle reconstruction subjects with ACL injuries. Findings were similar between the groups after one year and two years of surgical interventions.


Stretching globular polymers. II. Macroscopic cross-linked networks.
We expand upon the results for the force-extension behavior of single-collapsed polymer chains to consider the mechanical response of networks of cross-linked globular polymers in poor solvent. Force-strain curves are obtained under the affine deformation approximation for networked globules with both disordered and ordered globule conformations. Due to their large stored lengths, these networks would be capable of reaching extremely large strains. They also show anomalous nonmonotonic force-strain response, as a consequence of the nonmonotonic force-extension curves of their constituent globules. Finally, we consider the stability of ordered and disordered globules in these networks and propose means taken from biological and colloid science to stabilize networked globules.


Serological surveillance of healthcare workers to evaluate natural infection- and vaccine-derived immunity to SARS-CoV-2 during an outbreak in Dili, Timor-Leste.
Background Serosurveillance can be used to investigate the extent and distribution of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a population. Characterisation of humoral immune responses gives insight into whether immunity is infection- or vaccine-derived. Methods A longitudinal study of health care workers (HCWs) in Dili, Timor-Leste, was conducted during vaccine rollout (ChAdOx1) and a concurrent SARS-CoV-2 outbreak. Results A total of 324 HCWs were included at baseline (April-May 2021). Out of those, 32 (9.9%) were seropositive for anti-nucleocapsid protein (anti-N) IgG antibodies, indicating a significant sub-clinical infection among HCWs early in the local outbreak. Follow-up was conducted in 157 (48.5%) participants (July-September 2021), by which time there had been high uptake of vaccination (91.7%), and 86.0% were seropositive for anti-spike protein antibodies. Acquisition of anti-N antibodies was observed in partially vaccinated HCWs (30/76, 39.5%), indicating some post-dose-1 infections. Discussion Serosurveillance of HCWs may provide early warning of SARS-CoV-2 outbreaks and should be considered in non-endemic settings, particularly where there is limited availability/uptake of testing for acute infection. Characterisation of humoral immune responses may be used to assess vaccine impact and coverage. Such studies should be considered in national and international efforts to investigate and mitigate against future emerging pathogens.


Acellular dermal matrix and subepithelial connective tissue grafts for root coverage: A systematic review.
The aim of this systematic review was to evaluate whether patients with gingival recession would benefit from an acellular dermal matrix graft (ADMG) in ways that are comparable to the gold standard of the subepithelial connective tissue graft (SCTG). A systematic review and meta-analysis comparing ADMG to SCTG for the treatment of Miller Class I and II recession defects was conducted according to PRISMA guidelines. PubMed, Excerpta Medica Database, and Cochrane Central Register of Controlled Trials databases were searched up to March 2016 for controlled trials with minimum 6 months duration. The primary outcome was root coverage; secondary outcomes included attachment level change, keratinized tissue (KT) change, and patient-based outcomes. Both authors independently assessed the quality of each included trial and extracted the relevant data. From 158 potential titles, 17 controlled trials were included in the meta-analysis. There were no differences between ADMG and SCTG for mean root coverage, percent root coverage, and clinical attachment level gain. ADMG was statistically better than SCTG for gain in width of KT (-0.43 mm; 95% confidence interval: -0.72, -0.15). Only one study compared patient-based outcomes. This review found that an ADMG would be a suitable root coverage substitute for an SCTG when avoidance of the second surgical site is preferred.


[Comprehensive treatment of aquariculture water pollution by flocculant and complex strain].
In order to purify aquariculture water, decrease fish-disease and sewage discharge, the purification efficiency of several types of flocculants such as PFS, PDMDAAC, EM, and combining PFS-PDMDAAC, PFS-PDMDAAC-EM used for treatment of soft-shelled turlle pond water were studied, and optimal mathematical of water qualities effected by several types of purification method were established. The results showed that the comprehensive treatment had the best purifcation efficiency, the flocculation rate was above 98%, CODcr removed rate was above 95%, BOD5/CODcr of pond water and effluent decreased from 0.61 and 0.51 to 0.24 and 0.29 respectively, the biodegradable matter in waters have been effectively removed, when 30 mg.L-1 PFS, 0.5 mg.L-1 PDMDAAC and 30 ml.m-3 EM were added. The various major water qualities were keeded stabilization and had attained special aquariculture water quality standard. The water qualities of pond water and that of effluent were showed no difference, which had attained pollution-free discharge and ecological equilibrium aquariculture.


Case study of an adolescent spinal cord injured patient.
An adolescent SCI patient's constant resistant behaviors caused caregivers to reconsider the usual rehabilitation nursing focus of teaching for independence. Teaching goals were changed to focus on the most essential information and behaviors that would be needed for safe care after discharge. The family and the patient were able to learn these, and although no further progress has been made toward independence, it appears that the patient is being safely cared for in the community.


Epstein-Barr virus noncoding RNAs from the extracellular vesicles of nasopharyngeal carcinoma (NPC) cells promote angiogenesis via TLR3/RIG-I-mediated VCAM-1 expression.
Viral noncoding RNAs (Epstein-Barr virus-encoded RNAs, EBERs) are believed to play a critical role in the progression of lymphoma and nasopharyngeal carcinoma (NPC). However, the accurate mechanisms accounting for their oncogenic function have not been elucidated, especially in terms of interaction between tumor cells and mesenchymal cells. Here, we report that, in addition to NPC cells, EBERs are also found in endothelial cells in Epstein-Barr virus (EBV)-infected NPC parenchymal tissues, which implicates NPC-derived extracellular vesicles (EVs) in transmitting EBERs to endothelial cells. In support of this hypothesis, we first ascertained if EBERs could be transferred to endothelial cells via EVs isolated from NPC culture supernatant. Then, we clarified that EVs-derived EBERs could promote angiogenesis through stimulation of VCAM-1 expression. Finally, we explored the involvement of EBER recognition by TLR3 and RIG-I in NPC angiogenesis. Our observations collectively illustrate the significance and mechanism of EVs-derived EBERs in angiogenesis and underlie the interaction mechanisms between EBV-infected NPC cells and the tumor microenvironment.


[Laparotomy with splenectomy in Hodgkin's disease. Critical study of results in 123 patients].
123 laparotomies with splenectomy have been performed in 3 groups of patients. 1. 40 patients with infra-diaphragmatic relapses afer mantle field radiotherapy for supra-diaphragmatic disease. 2. 45 previously untreated patients. 3. 37 stages III B patients treated by intensive chemotherapy before splenectomy. Anatomical findings suggest that hematogenous dissemination may be responsible for spleen involvement and that spleen involvement may be suppressed by chemotherapy. In view of these data, chemotherapy in association with radiotherapy seems to be justified even in patients with apparently localised forms since the spleen may be involved in such patients at clinical presentation of the disease. From the preliminary results of studies which aim to appreciate the effectiveness of chemotherapy on splenic lesions, the need for routine laparotomy and splenectomy should be reevaluated.


Managing antibiotic resistance in nontuberculous mycobacterial pulmonary disease: challenges and new approaches.
Introduction: The incidence and prevalence rates of nontuberculous mycobacterial (NTM) pulmonary disease have been continuously increasing worldwide. However, the rate of successful treatment of this disease greatly needs improving, particularly when intrinsic (natural) drug resistance and acquired drug resistance in NTM pulmonary disease are associated with poor outcomes for patients. Areas covered: This review covers the major pathogens that cause NTM pulmonary disease caused by Mycobacterium avium complex, Mycobacterium abscessus, and Mycobacterium kansasii; the key drugs and recommended regimens used in the treatment of NTM pulmonary disease; the factors that contribute to resistance to the key drugs, including genetic factors and monotherapy; and the treatment strategies, including revised antibiotic regimens and surgery, that can be used to treat drug-resistant NTM pulmonary disease. Expert opinion: To avoid and overcome drug resistance in NTM pulmonary disease, the appropriate guideline-based treatments are essential, and clinical studies to evaluate new or repurposed drugs are urgently needed.


Regression-Based Network Estimation for High-Dimensional Genetic Data.
Given the continuous advancement in genome sequencing technology, large volumes of gene expression data can be easily obtained. However, the corresponding increase in genetic information necessitates adoption of a new approach for network estimation. Data dimensions increase with the progress in genome sequencing technology, thereby making it difficult to estimate gene networks by causing multicollinearity. Furthermore, such a problem also occurs when hub nodes exist, where gene networks are known to have regulator genes that can be interpreted as hub nodes. This study aims at developing methods that demonstrate good performance when handling high-dimensional data with hub nodes. We propose regression-based approaches as feasible solutions in this article. Elastic-net and adaptive elastic-net penalty regressions were applied to compensate for the disadvantages of existing regression-based approaches employing LASSO or adaptive LASSO. Experiments were performed to compare the proposed regression-based approaches with other conventional methods. We confirmed the superior performance of the regression-based approaches and applied it to actual genetic data to verify the suitability to estimate gene networks. As results, robustness of the proposed methods was demonstrated with respect to high-dimensional gene expression data.


Different abilities of the four FGFRs to mediate FGF-1 translocation are linked to differences in the receptor C-terminal tail.
Members of the fibroblast growth factor family bind to one or more of the four closely related membrane-spanning FGF receptors. In addition to signaling through the receptors, exogenous FGF-1 and FGF-2 are endocytosed and translocated to the cytosol and nucleus where they stimulate RNA and DNA synthesis. Here we have studied the ability of the four FGF receptors to facilitate translocation of exogenous FGF-1 to the cytosol and nucleus. FGFR1 and FGFR4 were able to mediate translocation, whereas FGFR2 and FGFR3 completely lacked this ability. By analyzing mutant FGFRs we found that the tyrosine kinase domain could be deleted from FGFR1 without abolishing translocation, whereas the C-terminal tail of the FGFRs, constituted by approximately 50 amino acids downstream of the kinase domain, plays a crucial role in FGF-1 translocation. Three amino acids residues within the C-terminal tail were found to be of particular importance for translocation. For FGFR2, the two amino acid substitutions Q774M and P800H were sufficient to enable the receptor to support FGF-1 translocation. The results demonstrate a striking diversity in function of the four FGFRs determined by their C-terminal domain.


Enterococcus faecium FC-K Derived from Kimchi Is a Probiotic Strain That Shows Anti-Allergic Activity.
A rise in the occurrence of allergic diseases is attributed to the dysregulated balance of type 1/type 2 immunity, where type 2 T-helper (Th2) cells predominate over type 1 T-helper (Th1) cells, leading to an abnormally increased production of IgE in response to unharmful antigens. Kimchi, a traditional Korean fermented food, is a rich source of beneficial lactic acid bacteria. In this study, we investigated the ability of Enterococcus faecium FC-K derived from kimchi to induce type I immunity in the presence of Th2 polarizing conditions in vitro and in vivo. Stimulation of mouse peritoneal macrophages with E. faecium FC-K induced the production of tumor necrosis factor alpha, interleukin (IL)-6, and IL-12. Under the in vitro Th2 conditions in which splenic T cells were activated in the presence of IL-4, E. faecium FC-K enhanced the ability of T cells to produce interferon (IFN)-γ. Using the ovalbumin (OVA)-induced allergy model, male BALB/c mice receiving E. faecium FC-K reduced the serum level of total IgE, but not that of OVA-specific IgE. Furthermore, the population of activated splenic B cells during OVA immunization was decreased in E. faecium FC-K-treated mice, accounting for a reduction of total IgE in the serum. Restimulating splenocytes from OVA-immunized mice with OVA ex vivo resulted in an increased production of IFN-γ, with no effect on IL-4, in E. faecium FC-Ktreated mice. These observations provide the evidence that E. faecium FC-K can be a beneficial probiotic strain that can modulate the Th2-mediated pathologic response.


Coronary blood flow in patients with cardiac syndrome X.
Epicardial coronary arteries are normal in patients with cardiac syndrome X. It is, however, unclear whether there is an abnormality at the level of microvascular circulation. In this study, our aim was to evaluate the epicardial coronary blood flow and myocardial perfusion in patients with cardiac syndrome X. Two hundred and three patients (mean age 53+/-10 years, 85 men) were included in the study. The diagnosis of cardiac syndrome X was made in patients who had a complaint of typical anginal chest pain and had ischemic findings on either myocardial perfusion scintigraphy or a treadmill exercise test, and whose coronary angiograms did not reveal any pathology. Fifty patients (mean age 54+/-11 years, 24 men) who had a complaint of typical anginal chest pain and had a normal myocardial perfusion test and normal coronary arteries were recruited as the control group. Epicardial coronary blood flow was evaluated with the thrombolysis in myocardial infarction frame count method and myocardial perfusion was evaluated with the myocardial blush grade method. A myocardial blush grade of < or =2 in any vessel was considered abnormal. Although the right coronary thrombolysis in myocardial infarction frame count was higher in patients with syndrome X (14.9+/-7.6 vs. 11.7+/-4.4 in controls; P=0.014), there were no statistically significant differences between the groups in terms of mean thrombolysis in myocardial infarction frame count in the coronary arteries. Abnormal myocardial blush grade was present in 85 patients (42.3%) with syndrome X, and in 17 patients (34.7%) in the control group (P>0.05). We found that the epicardial coronary blood flow, as assessed by thrombolysis in myocardial infarction frame count, and myocardial perfusion, as assessed by myocardial blush grade, were normal in patients with cardiac syndrome X.


Development of MWCNT/Magnetite Flexible Triboelectric Sensors by Magnetic Patterning.
The fabrication of low-electrical-percolation-threshold polymer composites aims to reduce the weight fraction of the conductive nanomaterial necessary to achieve a given level of electrical resistivity of the composite. The present work aimed at preparing composites based on multiwalled carbon nanotubes (MWCNTs) and magnetite particles in a polyurethane (PU) matrix to study the effect on the electrical resistance of electrodes produced under magnetic fields. Composites with 1 wt.% of MWCNT, 1 wt.% of magnetite and combinations of both were prepared and analysed. The hybrid composites combined MWCNTs and magnetite at the weight ratios of 1:1; 1:1/6; 1:1/12; and 1:1/24. The results showed that MWCNTs were responsible for the electrical conductivity of the composites since the composites with 1 wt.% magnetite were non-conductive. Combining magnetite particles with MWCNTs reduces the electrical resistance of the composite. SQUID analysis showed that MWCNTs simultaneously exhibit ferromagnetism and diamagnetism, ferromagnetism being dominant at lower magnetic fields and diamagnetism being dominant at higher fields. Conversely, magnetite particles present a ferromagnetic response much stronger than MWCNTs. Finally, optical microscopy (OM) and X-ray micro computed tomography (micro CT) identified the interaction between particles and their location inside the composite. In conclusion, the combination of magnetite and MWCNTs in a polymer composite allows for the control of the location of these particles using an external magnetic field, decreasing the electrical resistance of the electrodes produced. By adding 1 wt.% of magnetite to 1 wt.% of MWCNT (1:1), the electric resistance of the composites decreased from 9 × 104 to 5 × 103 Ω. This approach significantly improved the reproducibility of the electrode's fabrication process, enabling the development of a triboelectric sensor using a polyurethane (PU) composite and silicone rubber (SR). Finally, the method's bearing was demonstrated by developing an automated robotic soft grip with tendon-driven actuation controlled by the triboelectric sensor. The results indicate that magnetic patterning is a versatile and low-cost approach to manufacturing sensors for soft robotics.


Sclerosing hemangioma of the lung. Granulomatous variant.
We present a case of granulomatous sclerosing hemangioma of the lung in a 43-year-old white woman in whom a pulmonary nodule was found on a routine chest roentgenogram. Surgical resection of a well-circumscribed pulmonary nodule was performed. Histologically, the tumor showed the typical features of sclerosing hemangioma with the unusual feature of a florid granulomatous reaction. Immunohistochemical studies using antibodies for epithelial membrane antigen decorated the tumoral cells, while factor VIII was positive in the vascular structure. Histochemical stains for microorganisms yielded negative results.


Sedation and analgesia in patients on mechanical ventilation in pediatric intensive care units in Argentina.
Children in pediatric intensive care units (PICUs) are exposed to experiencing pain, stress and anxiety due to their disease, treatment or care setting. Adequate sedation and analgesia are key to their care, particularly in patients requiring mechanical ventilation (MV). To determine the usual practice in sedation and analgesia management in patients requiring MV in PICUs in Argentina. Descriptive, crosssectional, multi-center study conducted by means of e-mailed surveys. A total of 45 PICUs were surveyed, 18% (N= 8) of which follow a sedation and analgesia protocol strictly, while 58% (N= 26) follow an "implied" protocol based on routine practice. The most commonly used drugs were midazolam, for sedation, and fentanyl, for analgesia. In 31% (N= 14) of the PICUs, sedation was monitored through assessment scales (modified Ramsay and/or Comfort scales). In 4% (N= 2) of units, daily, scheduled interruptions of sedation was implemented. In patients who are difficult to sedate, dexmedetomidine was the most commonly used adjuvant. In 73% (N= 33) of the units, neuromuscular blocking agents were used in compliance with precise guidelines and under clinical monitoring. In 20% (N= 9) of the PICUs there was a sedation and analgesia weaning protocol in place, and morphine and lorazepam are the most commonly used drugs. Only a low percentage of surveyed PICUs had a protocol in place for the routine management of sedation and analgesia in patients on MV.


Sign language and autism.
Research findings and issues in teaching sign language to nonspeaking autistic children are reviewed. Data on over 100 children indicate that nearly all autistic children learn receptive and expressive signs, and many learn to combine signs. These children also exhibit marked improvement in adaptive behaviors. Speech skills are acquired by fewer children and may be developed through simultaneous speech and sign training. Possible explanations for these results are given, together with suggestions for future research and data collection. Recommended innovations include exposure to fluent signers and training in discourse and code-switching. Different sign language teaching methods need to be investigated more fully, including emphasis on training sign language within the children's total environment and with greater staff and parental participation.


Discovery of Novel Terpenoids from the Basidiomycete Pleurotus ostreatus through Genome Mining and Coculture Optimization.
In our previous work, postredienes A-C, three unusual linear sesterterpenes with high antifungal activities, were isolated from Pleurotus ostreatus SY10 when cocultured with Trametes robiniophila SY636. However, their titers were low, and exploration of newly biosynthesized trace analogues is required. Herein, genome mining analysis predicted that 17 gene clusters are involved in terpenoid biosynthesis in P. ostreatus. Thus, coculture conditions for strains SY10 and SY636 were optimized using a single-factor test and Box-Behnken design. As a result, the titers of postredienes A-C were increased by over 2.5-fold, reaching 1.28 to 8.40 mg/L. Moreover, five new terpenoids, named postredienes D-H (1-5), were successfully isolated. Compound 1 exhibited activities against the human pathogenic fungi Candida albicans and Cryptococcus neoformans comparable to those of amphotericin B. Compound 2 represents a novel sesterterpene with a five-membered ring at C-7. The absolute configurations of 1-5 were elucidated by making the methoxyphenylacetic acid esters and acetonide derivatives, combined with ECD and NMR calculation. Two potential gene clusters and relevant biosynthetic pathways for 1-5 were subsequently proposed based on real-time reverse transcription-quantitative PCR (RT-qPCR) analysis. The current study provides new insights into the research of terpenoid biosynthesis genes in P. ostreatus and other basidiomycetes.


A Modified Lateral Approach for Total Knee Replacement in Type 2 Valgus Deformity.
Total knee replacement for patients with osteoarthritis and valgus deformity remains challenging, with soft tissue balance often difficult to achieve. Most orthopedic surgeons use the medial parapatellar approach for total knee replacement. However, the lateral approach described in this case allows direct access to the pathology. The valgus deformity is corrected by using a modified lateral parapatellar arthrotomy with a staged and gradual release of the contracted lateral capsuloligamentous structures and the iliotibial tract. A Z-shaped dissection of the lateral retinaculum and careful dissection and preservation of the infrapatellar fat pad is performed. The creation of this laterally based vascularized flap provides the necessary tissue to cover the soft tissue gap resulting on the lateral aspect of the knee after valgus correction. The lateral approach has advantages, including ligament balancing and preservation of the medial retinaculum and the medial neurovascular structures for the supply of the patella. However, this approach should be used with caution by experienced surgeons. [Orthopedics. 2017; 40(5):313-316.].


Unusual electronic properties of clean and disordered zigzag graphene nanoribbons.
We revisit the problem of electron transport in clean and disordered zigzag graphene nanoribbons, and expose numerous hitherto unknown peculiar properties of these systems at zero energy, where both sublattices decouple because of chiral symmetry. For clean ribbons, we give a quantitative description of the unusual power-law dispersion of the central energy bands and of its main consequences, including the strong divergence of the density of states near zero energy, and the vanishing of the transverse localization length of the corresponding edge states. In the presence of off-diagonal disorder, which respects the lattice chiral symmetry, all zero-energy localization properties are found to be anomalous. Recasting the problem in terms of coupled Brownian motions enables us to derive numerous asymptotic results by analytical means. In particular the typical conductance gN of a disordered sample of width N and length L is shown to decay as exp(-CNw√L), for arbitrary values of the disorder strength w, while the relative variance of ln gN approaches a non-trivial constant KN. The dependence of the constants CN and KN on the ribbon width N is predicted. From the mere viewpoint of the transfer-matrix formalism, zigzag ribbons provide a case study with many unusual features. The transfer matrix describing propagation through one unit cell of a clean ribbon is not diagonalizable at zero energy. In the disordered case, we encounter non-trivial random matrix products such that all Lyapunov exponents vanish identically.


Recognition of depressive symptoms in the elderly: what can help the patient and the doctor.
The general public heavily underrecognizes depression and depressive symptoms. This underrecognition is more pronounced among elderly people, and this study is an initial attempt to quantify the problem in a Greek elderly sample. Additionally the authors attempt to identify patient-related factors, which can assist a subject to recognize the depressive symptoms and the general practitioner to note their existence. Members of senior citizen centers (n = 682) participated in presentations about "depression in the elderly" and completed a questionnaire including the GDS-4 scale, four questions concerning depression risk factors and a question concerning a recent visit to a physician for depressive symptoms. Amongst those participating, 35.8% presented depressive symptoms (GDS-4 > or = 2). The calculated rate for recognition of depression in the studied population was very low (17.3%). Patients with depressive symptoms were more often females and had a higher proportion of past history of depression and a lack of social support. Patients with a past history of depression and more severe forms of illness consulted a doctor more frequently. Finally, subjects suffering from depressive symptoms and comorbid medical illness were characterized by a higher proportion of past history, lack of support, and existence of multiple risk factors. The authors propose that the inclusion in public campaigns of activities with an experiential dimension, e.g., patient videos and the use of a very simple screening tool, such as the GDS-4 scale by general practitioners (GP), could be helpful in improving the recognition of depressive symptoms by the patient and his/her relatives and its diagnosis by the doctor. This proposition awaits formal proof in future studies.


[The effects of protein and amino acids on DNA synthesis in regenerating liver].
In order to estimate the effects of protein and amino acids on regenerating liver, the induction of enzymes involved in synthesis of DNA was studied in rats fed protein free diet. In the regenerating livers of rats of the protein free diet, increase of liver weight and DNA content were stopped 48 hours after hepatectomy, and induction of DNA synthesizing enzymes such as dCMP deaminase, ribonucleotide reductase, and thymidine kinase were depressed and shortened. On the other hand, induction of protein or RNA synthesizing enzymes such as polyamine, ornithine decarboxylase, and tyrosine aminotransferase were not depressed by protein deprivation. The results indicate that protein deprivation inhibits the DNA synthesizing enzymes specifically, and regenerating liver cells can not enter S phase of cell cycle. When rats were maintained solely by total parenteral nutrition after hepatectomy, amino acids were essential for induction of DNA synthesizing enzymes. In particular, induction of these enzymes were regulated by 7 amino acids include Val, Leu, Ile, Met, Trp, Phe, and Thr, and most of these plasma amino acid levels were depressed after hepatectomy. By administration of amino acids for 12 hours just after hepatectomy, the DNA synthesizing enzymes were almost normally induced. This suggests that amino acids administration just after hepatectomy is effective to induce the DNA synthesizing enzymes for hepatic regeneration.


A controlled study of the effectiveness of public health HIV partner notification services.
Health departments inconsistently provide partner notification services to persons with HIV. We surveyed a randomly selected sample of 370 patients at the largest HIV clinic in Washington State, USA, using a self-administered anonymous questionnaire. Patients who reported talking to health department staff about partner notification were more likely to report notifying at least one sex partner following their HIV diagnosis than patients who did not talk to health department staff (68 vs. 45%, odds ratio = 2.5, 95% confidence interval = 1.6-3.9).


Ling classification describes endoscopic progressive process of achalasia and successful peroral endoscopy myotomy prevents endoscopic progression of achalasia.
To verify the hypothesis that the Ling classification describes the endoscopic progressive process of achalasia and determine the ability of successful peroral endoscopic myotomy (POEM) to prevent endoscopic progression of achalasia. We retrospectively reviewed the endoscopic findings, symptom duration, and manometric data in patients with achalasia. A total of 359 patients (197 women, 162 men) with a mean age of 42.1 years (range, 12-75 years) were evaluated. Symptom duration ranged from 2 to 360 mo, with a median of 36 mo. Patients were classified with Ling type I (n = 119), IIa (n = 106), IIb (n = 60), IIc (n = 60), or III (n = 14), according to the Ling classification. Of the 359 patients, 349 underwent POEM, among whom 21 had an endoscopic follow-up for more than 2 years. Pre-treatment and post-treatment Ling classifications of these 21 patients were compared. Symptom duration increased significantly with increasing Ling classification (from I to III) (P < 0.05), whereas lower esophageal sphincter pressure decreased with increasing Ling type (from I to III) (P < 0.05). There was no difference in sex ratio or onset age among the Ling types, although the age at time of diagnosis was higher in Ling types IIc and III than in Ling types I, IIa, and IIb. Of the 21 patients, 19 underwent high-resolution manometry both before and after treatment. The mean preoperative and postoperative lower esophageal sphincter pressure were 34.6 mmHg (range, 15.3-59.4 mmHg) and 15.0 mmHg (range, 2.1-21.6 mmHg), respectively, indicating a statistically significant decrease after POEM. All of the 21 patients were treated successfully by POEM (postoperative Eckardt score ≤ 3) and still had the same Ling type during a mean follow-up period of 37.8 mo (range, 24-51 mo). The Ling classification represents the endoscopic progressive process of achalasia and may be able to serve as an endoscopic assessment criterion for achalasia. Successful POEM (Eckardt score ≤ 3) seems to have the ability to prevent endoscopic evolvement of achalasia. However, studies with larger populations are warranted to confirm our findings.


Influence of LY 300164 alone or in combination with carbamazepine or diphenylhydantoin on the body temperature in mice.
This study was aimed at evaluating the body temperature of mice following the injection of LY 300164, an AMPA/kainate receptor antagonist, alone or in combination with carbamazepine or diphenylhydantoin. LY 300164, injected alone at the dose of 2 mg/kg, produced a potent hypothermic effect between 15 and 30 min, or 60 and 90 min, after the drug administration. The combined treatment of LY 300164 (2 mg/kg) with diphenylhydantoin (3.6 mg/kg) resulted in a significant decrease of body temperature at the time period between 0 and 30 min, whilst LY 300164 (2 mg/kg) co-administered with carbamazepine (5 mg/kg) did not affect the animal temperature. Moreover, either diphenylhydantoin (11.8 mg/kg) or carbamazepine (15.8 mg/kg) injected alone exerted the hypothermic effects elicited at times ranging between 0 and 15 min, or 60 and 90 min, after the respective drug dose administration. In conclusion, hypothermia induced by LY 300164 along with its neuroprotective effects, may be useful in various brain conditions related with neuronal loss in which hypothermia offers some profitable effects, prolonging a survival rate of neurons in the central nervous system.


Application of Bayesian decomposition for analysing microarray data.
Microarray and gene chip technology provide high throughput tools for measuring gene expression levels in a variety of circumstances, including cellular response to drug treatment, cellular growth and development, tumorigenesis, among many other processes. In order to interpret the large data sets generated in experiments, data analysis techniques that consider biological knowledge during analysis will be extremely useful. We present here results showing the application of such a tool to expression data from yeast cell cycle experiments. Originally developed for spectroscopic analysis, Bayesian Decomposition (BD) includes two features which make it useful for microarray data analysis: the ability to assign genes to multiple coexpression groups and the ability to encode biological knowledge into the system. Here we demonstrate the ability of the algorithm to provide insight into the yeast cell cycle, including identification of five temporal patterns tied to cell cycle phases as well as the identification of a pattern tied to an approximately 40 min cell cycle oscillator. The genes are simultaneously assigned to the patterns, including partial assignment to multiple patterns when this is required to explain the expression profile. The application is available free to academic users under a material transfer agreement. Go to http://bioinformatics.fccc.edu/ for more details.


Motor neuron-specific RhoA knockout delays degeneration and promotes regeneration of dendrites in spinal ventral horn after brachial plexus injury.
Dendrites play irreplaceable roles in the nerve conduction pathway and are vulnerable to various insults. Peripheral axotomy of motor neurons results in the retraction of dendritic arbors, and the dendritic arbor can be re-expanded when reinnervation is allowed. RhoA is a target that regulates the cytoskeleton and promotes neuronal survival and axon regeneration. However, the role of RhoA in dendrite degeneration and regeneration is unknown. In this study, we explored the potential role of RhoA in dendrites. A line of motor neuronal RhoA conditional knockout mice was developed by crossbreeding HB9Cre+ mice with RhoAflox/flox mice. We established two models for assaying dendrite degeneration and regeneration, in which the brachial plexus was transection or crush injured, respectively. We found that at 28 days after brachial plexus transection, the density, complexity, and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice were slightly decreased compared with that in Cre mice. Dendrites underwent degeneration at 7 and 14 days after brachial plexus transection and recovered at 28-56 days. The density, complexity, and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice recovered compared with results in Cre mice. These findings suggest that RhoA knockout in motor neurons attenuates dendrite degeneration and promotes dendrite regeneration after peripheral nerve injury.


CD40 ligand-CD40 interaction induces chemokines in cervical carcinoma cells in synergism with IFN-gamma.
Cellular immunity plays a major role in controlling human papilloma virus infection and development of cervical carcinoma. Mononuclear cell infiltration possibly due to the action of chemokines becomes prominent in the tumor tissue. In fact, the macrophage chemoattractant protein-1, MCP-1, was detected in cervical squamous cell carcinoma in situ, whereas absent in cultured cells. From this, unknown environmental factors were postulated regulating chemokine expression in vivo. In this study, we show high CD40 expression on cervical carcinoma cells and CD40 ligand (CD40L) staining on attracted T cells in tumor tissue, suggesting a paracrine stimulation mechanism via CD40L-CD40 interactions. We therefore investigated chemokine synthesis in nonmalignant and malignant human papilloma virus-positive cell lines after CD40L exposure. Constitutive expression of MCP-1, MCP-3, RANTES, and IFN-gamma-inducible protein-10 was almost undetectable in all cell lines tested. CD40L was able to induce MCP-1 production; however, despite much higher CD40 expression in malignant cells, MCP-1 induction was significantly lower compared with nontumorigenic cells. After sensitization with IFN-gamma, another T cell-derived cytokine showing minimal effects on CD40 expression levels, CD40 ligation led to a more than 20-fold MCP-1 induction in carcinoma cell lines. An even stronger effect was observed for IFN-gamma-inducible protein-10. Our study highlights the synergism of T cell-derived mediators such as CD40L and IFN-gamma for chemokine responses in cervical carcinoma cells, helping to understand the chemokine expression patterns observed in vivo.


Decreased diacylglycerol metabolism enhances ERK activation and augments CD8+ T cell functional responses.
Modulation of T cell receptor signal transduction in CD8(+) T cells represents a novel strategy toward enhancing the immune response to tumor. Recently, levels of guanine exchange factors, RasGRP and SOS, within T cells have been shown to represent a key determinant in the regulation of the analog to the digital activation threshold of Ras. One important for regulating activation levels of RasGRP is diacylglycerol (DAG), and its levels are influenced by diacylglycerol kinase-ζ (DGKζ), which metabolizes DAG into phosphatidic acid, terminating DAG-mediated Ras signaling. We sought to determine whether DGKζ-deficient CD8(+) T cells demonstrated enhanced in vitro responses in a manner predicted by the current model of Ras activation and to evaluate whether targeting this threshold confers enhanced CD8(+) T cell responsiveness to tumor. We observed that DGKζ-deficient CD8(+) T cells conform to most predictions of the current model of how RasGRP levels influence Ras activation. But our results differ in that the EC(50) value of stimulation is not altered for any T cell receptor stimulus, a finding that suggests a further degree of complexity to how DGKζ deficiency affects signals important for Ras and ERK activation. Additionally, we found that DGKζ-deficient CD8(+) T cells demonstrate enhanced responsiveness in a subcutaneous lymphoma model, implicating the analog to a digital conversion threshold as a novel target for potential therapeutic manipulation.


[Clinical characteristics of elderly Japanese patients with amyotrophic lateral sclerosis; with special reference to the development of respiratory failure].
To clarify the characteristics of elderly-onset amyotrophic lateral sclerosis (ALS). We analyzed the pattern of progression of clinical symptoms and respiratory dysfunction in 26 sporadic ALS patients (19 men, 7 women; mean age 73.2 +/- 6.0 years) with onset at age 65 years or older (E-ALS). We compared the results with those of 28 ALS patients (20 men, 8 women; 53.7 +/- 7.6 years) with younger onset ALS (Y-ALS). Among E-ALS patients, the bulbar palsy type (BP) was the most common (11 patients, 42%) followed by the respiratory failure type (RF) (7 patients, 27%). In contrast, upper extremity type (UE) was the most common (14 patients, 50%) in Y-ALS patients. Mean vital capacity percentage (%VC) at the initial examination was 71.1 +/- 20.4% (vital capacity (VC): 2.12 +/- 0.85 L) in all E-ALS patients, 64.5 +/- 14.5% in BP, 58.1 +/- 5.1% in RF, 94.4 +/- 11.1% in lower extremity type (LE), and 73.9 +/- 30.2% in UE. In all Y-ALS patients, %VC was 90.1 +/- 14.0% (2.94 +/- 0.57 L). The initial % VC value in E-ALS was significantly lower than that in Y-ALS (p < 0.01). VC was lower in RF and BP among E-ALS patients. It was also lower in BP E-ALS patients than in BP Y-ALS patients. Mean period from initial symptom until first examination was significantly shorter in RF in both groups, followed by BP. Twenty-two patients with E-ALS and 26 with Y-ALS died from respiratory failure. Four patients with E-ALS and 2 with Y-ALS required a mechanical ventilator. The mean period until death or ventilation support was 20.9 +/- 10.4 months in E-ALS, and 38.8 +/- 21.1 months in Y-ALS. Significantly shorter survival was observed in E-ALS than Y-ALS (p<0.01). In E-ALS patients, the mean period until death or ventilation support was 21.4 +/- 9.1 months with BP, 10.3 +/- 7.6 months with RF, 29.8 +/- 4.0 months with LE, and 29.3 +/- 5.4 months with UE. This period was significantly shorter in RF patients in both groups, followed by BP patients (p< 0.05, 0.01). Time until death or ventilation support was significantly shorter in BP and UE patients with E-ALS than in those with Y-ALS (p< 0.05). In regard to the progression of respiratory function deterioration, early % VC was lower in E-ALS than in Y-ALS patients, and the period until VC fell below 1 L was shorter. The period until death was particularly short in elderly BP and RF patients, suggesting the possibility that the duration until death from respiratory failure is shorter in E-ALS, because of a decrease in respiratory reverse capacity that accompanies age.


Hypomagnesemia in the Cancer Patient.
Hypomagnesemia is a common medical problem that contributes to the morbidity and mortality of patients with cancer. This review summarizes magnesium physiology and highlights the mechanisms underlying magnesium disturbances due to cancer and cancer treatment. The causes of hypomagnesemia can be categorized according to the pathophysiologic mechanism: decreased intake, transcellular shift, gastrointestinal losses, and kidney losses. Patients with cancer are at risk for opportunistic infections, frequently experience cardiovascular complications, and often receive classes of medications that cause or exacerbate hypomagnesemia. Also, cancer-specific therapies are responsible for hypomagnesemia, including platinum-based chemotherapy, anti-EGF receptor mAbs, human EGF receptor-2 target inhibitors (HER2), and calcineurin inhibitors. Urinary indices, such as the fractional excretion of magnesium, can provide useful information about the etiology. The management of hypomagnesemia depends on the magnitude of hypomagnesemia and the underlying cause. We recommended checking serum magnesium at the beginning of treatment and as part of routine monitoring throughout cancer treatment. Opportunities exist for potential research and practice improvement, including further characterization of hypomagnesemia regarding the clinical effect on cancer outcomes, preventing hypomagnesemia in patients receiving high-risk anticancer agents, and developing effective therapeutic strategies.


Prevalence and characteristics of gastroesophageal reflux in children with otitis media in Isfahan, Iran.
Otitis media (OM) is the most common cause of childhood hearing loss and reason to visit the pediatrician. Furthermore, gastroesophageal reflux (GER) has been associated with a variety of upper aerodigestive tract symptoms or diseases, such as sinusitis, laryngitis, and otits. The objective of the present study was to determine the frequency of GER in children, aged 3 months to 7 years, with OM. This retrospective case-control study was conducted on 50 children with OM and 50 healthy children. Presence of GER as the main variables was diagnosed by clinical examination in all studied children using the questionnaires with 2 age-stratified versions of the pediatric GER disease symptoms for children 2 years old and younger, and children 3-7 years old. The prevalence of GER in children with OM and controls was 58% and 22% respectively (P = 0.0005). The frequency of irritability, congestion, and feeding complex in children with OM were significantly more than in control groups. Among children with recurrent acute OM (AOM), and chronic serous OM (CSOM) the prevalence of GER was significantly more than controls (61.1%, vs. 22% for AOM, P = 0.004, and 72.7% vs. 22%, P= 0.003). In children with AOM, regurgitation, vomiting, irritability and congestion were significantly higher than controls included. In children with CSOM, regurgitation, vomiting, and congestion were significantly higher than controls. Results show a significant association between GER and OM, AOM and CSOM in children with OM compares to healthy children. This shows that looking for GER in children with OM may help improving treatments outcomes.