Engineering the Compositional Architecture of Core-Shell Upconverting Lanthanide-Doped Nanoparticles for Optimal Luminescent Donor in Resonance Energy Transfer: The Effects of Energy Migration and Storage.
Förster Resonance Energy Transfer (FRET) between single molecule donor (D) and acceptor (A) is well understood from a fundamental perspective and is widely applied in biology, biotechnology, medical diagnostics, and bio-imaging. Lanthanide doped upconverting nanoparticles (UCNPs) have demonstrated their suitability as alternative donor species. Nevertheless, while they solve most disadvantageous features of organic donor molecules, such as photo-bleaching, spectral cross-excitation, and emission bleed-through, the fundamental understanding and practical realizations of bioassays with UCNP donors remain challenging. Among others, the interaction between many donor ions (in donor UCNP) and many acceptors anchored on the NP surface and the upconversion itself within UCNPs, complicate the decay-based analysis of D-A interaction. In this work, the assessment of designed virtual core-shell NP (VNP) models leads to the new designs of UCNPs, such as …@Er, Yb@Er, Yb@YbEr, which are experimentally evaluated as donor NPs and compared to the simulations. Moreover, the luminescence rise and decay kinetics in UCNP donors upon RET is discussed in newly proposed disparity measurements. The presented studies help to understand the role of energy-transfer and energy migration between lanthanide ion dopants and how the architecture of core-shell UCNPs affects their performance as FRET donors to organic acceptor dyes.


Multiple Intestinal Bacteria Associated with the Better Protective Effect of Bifidobacterium pseudocatenulatum LI09 against Rat Liver Injury.
Bifidobacterium pseudocatenulatum LI09 could protect rats from D-galactosamine- (D-GalN-) induced liver injury. However, individual difference in the protective effects of LI09 on the liver injury remains poorly understood. The present study is aimed at determining the multiple intestinal bacteria associated with the better protective effect of LI09 against D-GalN-induced rat liver injury. Two rat cohorts, i.e., the nonsevere and severe cohorts, were divided based on their liver injury severity. Higher level of ALB and lower levels of ALT, AST, TBA, TB, IL-5, and MIP-3α were determined in the nonsevere cohort than the severe cohort. The alpha diversity indices (i.e., observed species, Shannon, and Pielou indices) did not yield significant differences between the intestinal microbiota of the nonsevere and severe cohorts. The intestinal microbiota composition was different between the two cohorts. Ten phylotypes assigned to Bacteroides, Clostridia_UCG-014, Clostridium Lachnospiraceae, Lachnospiraceae_NK4A136, and Parabacteroides were closely associated with the nonsevere cohort, among which, ASV8_Lachnospiraceae_NK4A136 was the most associated one. At the structure level, two groups of phylotypes with most correlations were determined in the intestinal microbiota networks of the two cohorts. Among them, ASV135_Lachnospiraceae_NK4A136 was the most powerful gatekeeper in the microbiota network of the nonsevere cohort. In conclusion, some intestinal bacteria, e.g., Lachnospiraceae_NK4A136, Parabacteroides, and Clostridium, were associated with the better protective effect of LI09 against D-GalN-induced rat liver injury. They were likely to enhance the effectiveness of LI09, and their clinical application deserves further investigation.


[Difficulties in renal osteodystrophy treatment in patient undergoing long-term renal replacement therapy--a case study].
Abnormal mineral metabolism and altered bone structure and composition occur early in the course of chronic kidney disease. We present difficulties in renal osteodystrophy treatment in patient undergoing renal replacement therapy for twenty two years (dialysis, transplant, dialysis), which is not in the waiting list for kidney transplant (patient disagreement). Due to failure of conventional therapy of hyperparathyroidism (calcium, phosphate binders, vitamin D) he was needed parathyroidectomy twice. Now he presents a very low PTH level but hyperphosphatemia, hypercalcemia and calcium/phosphate product over upper limit. This disturbances led to extra skeletal calcification (skin, vessels, eyes - "red eyes syndrome", central nervous system). Even now having new phosphate binders we cannot keep plasma phosphate, calcium in normal range, probably due to inadequate diet and non-compliance. Effective therapy is still difficult in this patient.


The induction of activating transcription factor 3 (ATF3) contributes to anti-cancer activity of Abeliophyllum distichum Nakai in human colorectal cancer cells.
Recently, Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme. However, no specific pharmacological effects from A. distichum have been described. We performed in vitro study to evaluate anti-cancer properties of A. distichum and then elucidate the potential mechanisms. Cell viability was measured by MTT assay. ATF3 expression level was evaluated by Western blot or RT-PCR and ATF3 transcriptional activity was determined using a dual-luciferase assay kit after the transfection of ATF3 promoter constructs. In addition, ATF3-dependent apoptosis was evaluated by Western blot after ATF3 knockdown using ATF3 siRNA. Exposure of ethyl acetate fraction from the parts of A. distichum including flower, leaf and branch to human colorectal cancer cells, breast cancer cells and hepatocellular carcinoma reduced the cell viability. The branch extracts from A. distichum (EAFAD-B) increased the expression of activating transcription factor 3 (ATF3) and promoter activity, indicating transcriptional activation of ATF3 gene by EAFAD-B. In addition, our data showed that EAFAD-B-responsible sites might be between -147 and -85 region of the ATF3 promoter. EAFAD-B-induced ATF3 promoter activity was significantly decreased when the CREB site was deleted. However, the deletion of Ftz sites did not affect ATF3 promoter activity by EAFAD-B. We also observed that inhibition of p38MAPK and GSK3β attenuated EAFAD-B-mediated ATF3 promoter activation. Also, EAFAD-B contributes at least in part to increase of ATF3 accumulation. These findings suggest that the anti-cancer activity of EAFAD-B may be a result of ATF3 promoter activation and subsequent increase of ATF3 expression.


Cyclin D1 G870A polymorphism: Association with uterine leiomyoma risk and in silico analysis.
Uterine leiomyoma (UL) is the most common benign tumor causing considerable morbidity during the reproductive years in women. Cyclin D1 (CCND1) is a cell cycle regulatory protein that is required for the G1 phase, and increased expression levels of this protein may affect tumorigenesis. The present study aimed to assess the possible effect of the CCND1 G870A polymorphism on UL susceptibility. A total of 154 women with UL and 197 healthy women who were age-, body mass index (BMI)- and ethnicity-matched were genotyped for the CCND1 G870A (rs9344) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The effects of G870A transition on the structure of mRNA and proteins of CCND1 was evaluated using bioinformatics tools. The frequency of the CCND1 870AA genotype was significantly higher in women with UL compared with the control subjects, and the risk of UL was 1.4-fold higher in women with the AA genotype when compared with the GG genotype before and after adjusting for age, BMI, and ethnicity [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1-2 (P=0.02)]. The frequency of CCND1 870GA genotype was not significantly different between the two groups. The frequency of the CCND1 870A allele was significantly higher in the women with UL when compared with the control subjects (57 vs. 48%; P=0.02). The in silico analysis revealed that the G870A transition may fundamentally alter the structure of the CCND1-mRNA. Thus, the CCND1 870AA genotype was associated with UL susceptibility in a sample of women from the southeast of Iran.


Suppression of myoclonus in SCA2 by piracetam.
We report on a 30-year-old patient with advanced cerebellar degeneration due to SCA2. He presented with severe myoclonus, which was resistant to conventional therapy and dramatically improved after administration of 12-18 gm/die piracetam. Piracetam may be considered in the treatment of refractory myoclonus in spinocerebellar degenerations.


Test-retest reliability of psychoactive substance abuse and dependence diagnoses in telephone interviews using a modified Diagnostic Interview Schedule-Substance Abuse Module.
The test-retest reliability of lifetime substance abuse and dependence diagnoses obtained by telephone interviewers was investigated. Trained personnel administered two identical interviews based on a modified Diagnostic Interview Schedule-Substance Abuse Module (DISSAM) approximately a week apart for 100 respondents, of whom 55 were receiving alcohol or other drug treatment and 45 and randomly selected from residential households in one Michigan county. The uncorrected agreement for all lifetime dependence diagnoses exceeded 93% for all six categories assessed and the more conservative chance corrected agreement (Cohen's Kappa coefficient kappa) was .92 (alcohol),.76 (marijuana),.87 (cocaine), and .71 (other opiates). Kappa coefficients for hallucinogens and heroin dependence could not be calculated due to low (i.e., 5% or less) base rates. Likewise, kappa was calculated only for a single abuse diagnosis, alcohol, with kappa = .42 and 95% agreement. In the interpretation of kappa, the standard applied was: kappa ranging from .41 to .60 represented moderate agreement, kappa ranging from .61 to .80 represented substantial agreement, and kappa ranging from .81 to 1.00 represented excellent agreement. Thus, test-retest reliability was excellent for lifetime alcohol and cocaine dependence and was substantial for lifetime marijuana and other opiates dependence. These results indicate that lifetime psychoactive substance abuse diagnoses can be obtained fairly reliably over the telephone using trained lay interviewers.


The Centre for Medical Humanities, Royal Free and University College Medical School, London, England.
The Centre for Medical Humanities is based within the Royal Free and University College Medical School. With a student body of more than 2,000, this large United Kingdom medical school benefits from being a fully integrated component of University College London. With its strong humanities and science faculties, University College London was founded more than 175 years ago to make education available to wider social and religious groups. With this background, it is logistically and ideologically well suited to sustaining a medical humanities program. The Centre's aims are to raise awareness of the field of medical humanities, to develop resources for the academic and teaching communities, and to build a broad and well-grounded educational program supported by sound educational principles and innovative research. Since 1998, the Centre and its predecessor, the Medical Humanities Unit, which was established by a group of medical educators with a diverse range of interests in the arts and humanities, has built interdisciplinary links and collaborative relationships with individuals and institutions within the university and beyond, nationally and internationally. These links and relationships have provided invaluable contributions and stimulus to the Centre's activities. The undergraduate educational program described in this article includes core and optional teaching throughout the curriculum, and a 1-year intercalated Bachelor of Science in Medical Humanities degree. For postgraduates, the Centre offers the United Kingdom's first continuing professional development accredited 2-day course in medical humanities, and an annual residential retreat open only to graduates of the course.


[Studies on longevity tea].
This paper reports the preparation, physical and chemical identification and content determination of Longevity Tea. The preparation process is advanced, the content determination is simple and accurate and thus can be taken as standards for the quality control of Longevity Tea.


Application of evoked potentials to the prediction of discharge status in minimally responsive patients: a pilot study.
Evoked potentials (EPs) have been shown to have useful prognostic value during the acute phase of traumatic and anoxic coma. We have hypothesized that EPs obtained in the subacute phase can be used to assess prognosis for functional recovery in minimally responsive patients with diffuse brain damage due to either brain trauma or anoxia. This pilot study correlated graded brainstem auditory evoked potentials (BAEPs) and upper extremity somatosensory evoked potentials (UESSEPs) with outcome grade based on the discharge Disability Rating Scale (DRS) score of 33 patients admitted to a responsiveness assessment program of a brain injury rehabilitation unit with an initial DRS score of 22 or greater. Results indicated a significant correlation with outcome grade for both the BAEP grade (P < .02) and the UESSEP grade (P < .02). The BAEP had a higher sensitivity and lower specificity, as false-positive exceeded false-negative predictions. The UESSEP tended to predict outcome more accurately and with a balanced number of false-positive and false-negative predictions. EPs were also found to be useful for detecting occult impairment of sensory function. This pilot study demonstrates that EPs performed near the time of admission to the rehabilitation unit can be useful in guiding the rehabilitation management of the minimally responsive patient by helping to predict functional recovery and to detect occult impairment of sensory systems.


Anomalous intensity dependence of optical reorientation in azo-dye-doped nematic liquid crystals.
The intensity dependence of optical nonlinearity in a nematic liquid crystal doped with an azo-dye is investigated. The reorientational part of the nonlinearity changes from self-defocusing to self-focusing character while the intensity passes through the saturation value of trans-cis photoisomerization. This observation, in accordance with previous models, indicates that the optical torque generated by the trans-isomers is of opposite sign than the torque generated by the cis-isomers. At very low intensities a further reorientational nonlinearity was found, which is attributed to light-induced orientational redistribution of adsorbed molecules at the surface.


Archimedes' principle in fluidized granular systems.
We fluidize a granular bed in a rectangular container by injecting energy through the lateral walls with high-frequency sinusoidal horizontal vibrations. In this way, the bed is brought to a steady state with no convection. We measured buoyancy forces on light spheres immersed in the bed and found that they obey Archimedes' principle. The buoyancy forces decrease when we reduce the injected energy. By measuring ascension velocities as a function of gamma, we can evaluate the frictional drag of the bed; its exponential dependence agrees very well with previous findings. Rising times of the intruders ascending through the bed were also measured, they increase monotonically as we increase the density.


Psychoanalytic reflections on a particular form of language distortion.
A female obsessive patient communicated with her sister via a distortion of the Hebrew language, in which she masculinized the feminine gender second person pronoun and certain nouns. This treatment of words is analyzed in terms ranging from the concrete to the metaphoric uses of language. Lacan's emphasis on the meaning of the word is explored and is seen as an amplification rather than a replacement of the object relations approach to language and metaphor.


Angiotensin converting enzyme inhibitors: inhibition of growth, a novel mechanism of action.
Angiotensin II, a known vasopressor agent, recently has been implicated as a growth factor in the heart and vascular smooth muscle. Angiotensin converting enzyme (ACE) inhibitors, which block angiotensin II synthesis, have been found to prevent or reverse cellular growth in the heart and vasculature--a novel mechanism of action. Further study is required to determine the precise mechanisms through which angiotensin II promotes growth as well as the mechanisms through which ACE inhibitors block growth. Large scale clinical trials are needed to delineate further the effectiveness of ACE inhibitors in humans, especially regarding vascular smooth muscle growth.


Identification and activation of novel biosynthetic gene clusters by genome mining in the kirromycin producer Streptomyces collinus Tü 365.
Streptomycetes are prolific sources of novel biologically active secondary metabolites with pharmaceutical potential. S. collinus Tü 365 is a Streptomyces strain, isolated 1972 from Kouroussa (Guinea). It is best known as producer of the antibiotic kirromycin, an inhibitor of the protein biosynthesis interacting with elongation factor EF-Tu. Genome Mining revealed 32 gene clusters encoding the biosynthesis of diverse secondary metabolites in the genome of Streptomyces collinus Tü 365, indicating an enormous biosynthetic potential of this strain. The structural diversity of secondary metabolisms predicted for S. collinus Tü 365 includes PKS, NRPS, PKS-NRPS hybrids, a lanthipeptide, terpenes and siderophores. While some of these gene clusters were found to contain genes related to known secondary metabolites, which also could be detected in HPLC-MS analyses, most of the uncharacterized gene clusters are not expressed under standard laboratory conditions. With this study we aimed to characterize the genome information of S. collinus Tü 365 to make use of gene clusters, which previously have not been described for this strain. We were able to connect the gene clusters of a lanthipeptide, a carotenoid, five terpenoid compounds, an ectoine, a siderophore and a spore pigment-associated gene cluster to their respective biosynthesis products.


Construction of miRNA-regulated drug-pathway network to screen drug repurposing candidates for multiple sclerosis.
Given the high disability rate of multiple sclerosis (MS), there is a need for safer and more effective therapeutic agents. Existing literature highlights the prominent roles of miRNA in MS pathophysiology. Nevertheless, there are few studies that have explored the usefulness of existing drugs in treating MS through potential miRNA-modulating abilities.The current investigation identifies genes that may exacerbate the risk of MS due to their respective miRNA associations. These findings were then used to determine potential drug candidates through the construction of miRNA-regulated drug-pathway network through genes. We uncovered a total of 48 MS risk pathways, 133 MS risk miRNAs, and 186 drugs that can affect these pathways. Potential MS risk miRNAs that are also regulated by therapeutic candidates were hsa05215 and hsa05152. We analyzed the properties of the miRNA-regulated drug-pathway network through genes and uncovered a number of novel MS agents by assessing their respective Z-values.A total of 20 likely drug candidates were identified, including human immunoglobulin, aspirin, alemtuzumab, minocycline, abciximab, alefacept, palivizumab, bevacizumab, efalizumab, tositumomab, minocycline, etanercept, catumaxomab, and sarilumab. Each of these agents were then explored with regards to their likely mechanism of action in treating MS.The current investigation provides a fresh perspective on MS biological mechanisms as well as likely treatment strategies.


Effect of probiotics on the meat flavour and gut microbiota of chicken.
To date, no report has demonstrated the use of beneficial microbes for contributing to the flavour characteristics and gut microbiota diversity of chicken. Here, we selected six probiotics obtained from our laboratory and supplemented them in six different combinations to 420 newborn male Qingjiaoma chickens under the same controlled living environment (60 birds, no probiotic supplements). The results showed that chicken supplemented with Bacillus species showed beneficial effects in body weight. Acetate is the major fermentation production in the chicken caecum, and chicken supplemented with Pediococcus pentosaceus had the average higher short chain fatty acids (SCFAs) contents. In chicken caecal microflora, the abundance of Bacteroidetes bacteria was positively correlated with the content of propionate, butyrate, and isobutyrate, whereas an increase in acetate content was positively correlated to the abundance of Firmicutes. Compared to chickens without probiotic supplement, chickens supplemented with P. pentosaceus had more characteristic flavour compounds in the sampled breast meat, especially higher concentrations of (E)-2-heptenal, (E,E)-2,4-nonadienal, and certain C6-C9 unsaturated fatty acids. This resulted in a stronger chicken-fatty or fatty odour which directly improved the flavour. These findings suggest that probiotics can improve chicken meat flavour and increase gut microbiota diversity.


HPLC Analysis of Phenolic Acids, Antioxidant Activity and in vitro Effectiveness of Green and Roasted Caffea arabica Bean Extracts: A Comparative Study.
Coffee is a popular drink; it is one of the most commercialized food products and a rich source of biologically active compounds that are important for human health. This study aimed to prove the anticancer activity of Green Coffee (GC) and Roasted Coffee (RC) bean aqueous extracts (Coffea arabica) on breast cancer adenocarcinoma cell line (MCF-7) and the safety of both extracts on normal Human Peripheral Blood Lymphocytes culture (HPBL). Total phenolic content for GC and RC extracts was measured and result of both extracts were (0.308±0.016 & 0.233±0.013mg/g) respectively. The phenolic acids were screened by HPLC at the wavelength of 254& 278 and 300 nm and 5-caffeoylquinic acids (Chlorogenic acid), the predominant form of phenolic acids, was identified in GC and RC samples. Ferric Reducing Antioxidant Power (FRAP) as well as the free radical scavenging activity (DPPH) proved the antioxidant properties of both extracts. The DPPH IC50 mean values of GC and RC extracts were (2.4±0.08, 2.3±0.16 µg/ml) respectively. Cytotoxicity of both extracts on MCF-7 cells were evaluated by neutral red uptake assay which showed the IC50 mean values (377±5.7,500±8.1 µg/ml) for GC and RC extracts respectively. The safety of both extracts (0, 125, 250, 500 µg/ml) on HPBL was evaluated in vitro using trypan blue exclusion method and DNA single strand breaks (alkaline comet assay). Result revealed non-significant cytotoxic difference (P<0.001) between cultures especially at lower doses of GC and RC extracts except the highest dose of GC and RC extract which showed slightly significant damage (P<0.001). This study proved that GC and RC aqueous extracts were found to be selectively cytotoxic in vitro to cancerous cells (MCF-7 cell line) causing cell death with no cytotoxicity on normal human lymphocytes especially at lower doses.


Poa secunda local collections and commercial releases: A genotypic evaluation.
The genetics of native plants influence the success of ecological restoration, yet genetic variability of local seed collections and commercial seed releases remains unclear for most taxa. Poa secunda, a common native grass species in Intermountain West grasslands and a frequent component of restoration seed mixes, is one such species. Here, we evaluate the genetic variation of local Poa secunda collections in the context of wild populations and commercial seed releases. We evaluated AFLP markers for seven Poa secunda collections made over a 4000-hectare area and four commercial releases (High Plains, MT-1, Opportunity, and Sherman). We compare the genetic distance and distribution of genetic variation within and between local collections and commercial releases. The extent and patterns of genetic variation in our local collections indicate subtle site differences with most variation occurring within rather than between collections. Identical genetic matches were usually, but not always, found within 5 m2 collection sites. Our results suggest that the genetic variation in two Poa secunda releases (High Plains and MT-1) is similar to our local collections. Our results affirm that guidelines for Poa secunda seed collection should follow recommendations for selfing species, by collecting from many sites over large individual sites.


Overexpression of IL-6 but not IL-8 increases paclitaxel resistance of U-2OS human osteosarcoma cells.
The cytokines IL-6, initially recognized as a regulator of immune and inflammatory response and IL-8, a potential regulator of angiogenesis, also regulate the growth of many tumor cells. Human cancer cells selected for multidrug resistance to common chemotherapeutic agents demonstrate increased expression of IL-6 and IL-8. To determine whether IL-6 or IL-8 overexpression contributes directly to the drug resistant phenotype, IL-6 or IL-8 cDNA were introduced into the paclitaxel sensitive human osteosarcoma cell line U-2OS using the pIRESneo bicistronic expression vector. Interleukin-6 and IL-8 transfectants were selected for either high IL-6 or IL-8 secretion and evaluated in drug resistance assays. Two IL-6 and two IL-8 secreting clones express IL-6 or IL-8 levels of 10 ng/ml and 1 ng/ml in culture, while parental U-2OS and pIRESneo vector transfected control cells express IL-6 and IL-8 levels of 0.005 ng/ml and 0.1 ng/ml, respectively. MTT cytotoxicity with IL-6 transfected cells demonstrates a five-fold increase in resistance to paclitaxel and a four-fold increase in resistance to doxorubicin as compared to U-2OS. There are no changes in mitoxantrone or topotecan resistance in the IL-6 transfectants as compared to parental U-2OS. Northern analysis of IL-6 transfectants demonstrates that the resistant phenotype is not related to increased levels of MDR-1, MRP-1, or LRP. Western analysis also confirms that P-glycoprotein levels are not altered in IL-6 transfectants. Further supporting an MDR-1 independent mechanism of drug resistance, verapamil cannot reverse paclitaxel resistance in transfected cells, findings further supported by rhodamine 123 exclusion data. Treatment of IL-6 transfected cells with paclitaxel, compared with drug-sensitive parental U-2OS, shows U-2OS(IL-6) are significantly more resistant to apoptosis induced by paclitaxel and exhibit decreased proteolytic activation of caspase-3. In contrast U-2OS(IL-8) transfectants demonstrate no appreciable increase in paclitaxel resistance when compared with parental cells. In summary, while both IL-6 and IL-8 are overexpressed in paclitaxel resistant cell lines, only IL-6 has the potential to contribute directly to paclitaxel and doxorubicin resistance in U-2OS. This resistance is through a non-MDR-1 pathway.


Cultural ecology of prehistoric parasitism on the Colorado Plateau as evidenced by coprology.
The study of coprolites (desiccated feces) is recognized as a viable method for analyzing parasitism of prehistoric peoples. Eight species of helminth parasites, including nematodes, cestodes, and acanthcephalans, have been recovered from archaeological sites on the Colorado Plateau. The comparative analysis of parasitological findings illustrates the effects of changing subsistence strategies and varying life-style on prehistoric human parasitism. This comparative study is based on the analysis of coprolites recovered from one Archaic hunter-gatherer site and two Anasazi agricultural villages. Hunter-gatherers are represented by coprolites from Dust Devil Cave in south-eastern Utah. Coprolites of prehistoric agriculturalists from Antelope House in Canyon de Chelly, Arizona, and from Salmon Ruin in northwestern New Mexico were studied. The results demonstrate that helminth parasitism increased with the advent of agriculture. Between the agricultural sites, differences in patterns of excreta disposal, foraging behavior, and local ecology resulted in pronounced variations in both percentage of coprolites containing parasite remains and the number of parasite species represented.


Dynamin-related proteins and Pex11 proteins in peroxisome division and proliferation.
The abundance and size of cellular organelles vary depending on the cell type and metabolic needs. Peroxisomes constitute a class of cellular organelles renowned for their ability to adapt to cellular and environmental conditions. Together with transcriptional regulators, two groups of peroxisomal proteins have a pronounced influence on peroxisome size and abundance. Pex11-type peroxisome proliferators are involved in the proliferation of peroxisomes, defined here as an increase in size and/or number of peroxisomes. Dynamin-related proteins have recently been suggested to be required for the scission of peroxisomal membranes. This review surveys the function of Pex11-type peroxisome proliferators and dynamin-related proteins in peroxisomal proliferation and division.


Disruption of cell-cell contact-mediated notch signaling via hydrogel encapsulation reduces mesenchymal stem cell chondrogenic potential: winner of the Society for Biomaterials Student Award in the Undergraduate Category, Charlotte, NC, April 15 to 18, 2015.
Cell-cell contact-mediated Notch signaling is essential for mesenchymal stem cell (MSC) chondrogenesis during development. However, subsequent deactivation of Notch signaling is also required to allow for stem cell chondrogenic progression. Recent literature has shown that Notch signaling can also influence Wnt/β-catenin signaling, critical for MSC differentiation, through perturbations in cell-cell contacts. Traditionally, abundant cell-cell contacts, consistent with development, are emulated in vitro using pellet cultures for chondrogenesis. However, cells are often encapsulated within biomaterials-based scaffolds, such as hydrogels, to improve therapeutic cell localization in vivo. To explore the role of Notch and Wnt/β-catenin signaling in the context of hydrogel-encapsulated MSC chondrogenesis, we compared signaling and differentiation capacity of MSCs in both hydrogels and traditional pellet cultures. We demonstrate that encapsulation within poly(ethylene glycol) hydrogels reduces cell-cell contacts, and both Notch (7.5-fold) and Wnt/β-catenin (84.7-fold) pathway activation. Finally, we demonstrate that following establishment of cell-cell contacts and transient Notch signaling in pellet cultures, followed by Notch signaling deactivation, resulted in a 1.5-fold increase in MSC chondrogenesis. Taken together, these findings support that cellular condensation, and establishment of initial cell-cell contacts is critical for MSC chondrogenesis, and this process is inhibited by hydrogel encapsulation.


Next generation antihistamines: therapeutic rationale, accomplishments and advances.
Antihistamines, among the most commonly prescribed drugs in the world, have evolved considerably since the first generation was introduced >50 years ago. The first generation antihistamines (e.g., chlorpheniramine, diphenhydramine, promethazine and hydroxyzine) are still widely available and in use today. These drugs have considerable sedative effects caused by their ability to cross the blood-brain barrier. The next generation of antihistamines to emerge in the market were devoid of these sedative effects; however, two (terfenadine and astemizole) have shown rare but lethal cardiotoxic side effects. The third generation antihistamines, metabolites of the earlier drugs, have demonstrated no cardiac effects of the parent drugs and are at least as potent. Many have exhibited superior pharmacokinetic and pharmacological profiles, including an improved onset of action and duration of effect. The clinical benefit of these newer oral antihistamines will clearly help improve the quality of life of patients with chronic allergies.


Endothelial-Dependent Vasomotor Dysfunction in Infants After Cardiopulmonary Bypass.
Cardiopulmonary bypass-induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants. Single-center prospective observational cohort pilot study. Pediatric cardiac ICU at a tertiary children's hospital. Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion. None. Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2-4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2-4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R = 0.43; p = 0.008). Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes.


Gel electrophoretic detection of 7,8-dihydro-8-oxoguanine and 7, 8-dihydro-8-oxoadenine via oxidation by Ir (IV).
Two gel electrophoretic methods are described for detection of 7, 8-dihydro-8-oxoguanine and 7,8-dihydro-8-oxoadenine based on their further oxidation with one-electron oxidants including IrCl62-and IrBr62-. The products of nucleobase oxidation lead to enhanced piperidine-sensitive cleavage and to highly visible stop points in a primer extension assay. 8-oxoG and 8-oxoA lesions may be distinguished by the latter's inability to be oxidized by IrBr62-compared to IrCl62-Comparison is also made to oxidation by MnO4-.


Gene Therapy in Hemophilia: A Transformational Patient Experience.
Hemophilia is a bleeding disorder caused by a single absent/defective gene and characterized by a lack of functional clotting factors. People with hemophilia may experience joint damage, pain, and psychological impairments, all of which could contribute to reduced health-related quality of life (HRQoL). The current standard of care is clotting factor replacement, which is associated with regular infusions; therefore, alternative treatments such as gene therapy (GT) are in development. GT involves the delivery of a functional copy of the clotting factor 8/9 gene by a single infusion into the patient's cells, enabling them to produce their own clotting factor VIII/IX. The impact of treatment on patients' HRQoL can be assessed using hemophilia-specific patient-reported outcome (PRO) measures. Since these measures were designed before the advent of GT, there is a need for updated individualized PRO measures. Patient groups and regulatory authorities emphasize the need for increased patient engagement when considering clinical trial design. Here, we provide patients' perspective on undergoing GT and discuss how to capture the patient voice when measuring the therapy's transformative impact.


Malaria in Honiara, Solomon Islands: reasons for presentation and human and environmental factors influencing prevalence.
During February and March 1995, out-patients attending health clinics and the Central Hospital in East Honiara, Guadalcanal, Solomon Islands, were surveyed with the aim of determining factors influencing the differing rates of malaria, the proportion of transmission occurring within the town, and the reasons for presentation. Three hundred and nine adult patients, who were sick and had blood smears taken, were asked about their general knowledge of malaria transmission. Of those interviewed, 120 were visited at their home in East Honiara, to determine variables. EpiInfo 5.1 was used in analysis. A history of fever alone was not a good indicator of parasitemia. Most precautions, including bed nets, window screens and personal precautions were of little benefit. Significant protection was afforded individuals and families with indoor kitchens. Patients not completing their antimalarial treatment fared worse in terms of parasitemia and malaria history. Most malaria/parasitemia was indigenous to Honiara. Many patients had a good knowledge of malaria transmission and mosquitos, but this did not translate into a lower rate of parasitemia or malaria.


ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling.
Key nuclear processes in eukaryotes, including DNA replication, repair, and gene regulation, require extensive chromatin remodeling catalyzed by energy-consuming enzymes. It remains unclear how the ATP demands of such processes are met in response to rapid stimuli. We analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly(ADP-ribose) to ADP-ribose. In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP. The nuclear source of ATP is essential for hormone-induced chromatin remodeling, transcriptional regulation, and cell proliferation.


Diagnosis, prescription, and prognosis of a bell-state filter by quantum process tomography.
We apply the techniques of quantum process tomography to characterize errors and decoherence in a prototypical two-photon operation, a singlet-state filter. The quantum process tomography results indicate a large asymmetry in the process and also the required operation to correct for this asymmetry. We quantify residual errors and decoherence of the filtering operation after this modification.


[Air pollution due to the burning of thermoplastics II (author's transl)].
Following on from the first publication, (12) concerning the burning of plastics, another 13 chemical pure polymers were burnt in an electric oven to determine the level of solid and gaseous air pollution caused by their stackgases. All 13 polymers are highly combustible but require different burning temperatures (300-900 degrees C) in order to be burnt completely (i.e. without ashrest). With the exception of PMMA and PTFE, all plastics leave a very heavy tar- and soot deposit after burning. At the other end of the scale, burning at low temperature (300 degrees C) gives rise to high concentrations of alipathic aldehyds. The pH of the exhaust-gases, dissolved in water, is neutral to strong acid (PTFE), and will cause a severe corrosion. The nitrogen-containing polymers pollute by forming cyanides, nitrogenoxides and ammonia. PTFE gives off high concentrations of fluorid into the air. PMMA decomposes in its monomer methylmethacrylate and forms large amounts of aliphatic aldehyds. ABS and SBR cause a styrene pollution.


Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells.
mTOR is a major biological switch, coordinating an adequate response to changes in energy uptake (amino acids, glucose), growth signals (hormones, growth factors) and environmental stress. mTOR kinase is highly conserved through evolution from yeast to man and in both cases, controls autophagy and cellular translation in response to nutrient stress. mTOR kinase is the catalytic component of two distinct multiprotein complexes called mTORC1 and mTORC2. In addition to mTOR, mTORC1 contains Raptor, mLST8 and PRAS40. mTORC2 contains mTOR, Rictor, mSIN1 and Protor-1. mTORC1 activates p70S6K, which in turn phosphorylates the ribosomal protein S6 and 4E-BP1, both involved in protein translation. mTORC2 activates AKT directly by phosphorylating Serine 473. pAKT(S473) phosphorylates TSC2 (tuberin) and inactivates it, preventing its association with TSC1 (hamartin) and the inhibition of Rheb, an activator of mTOR. pAKT also phosphorylates PRAS40, releasing it from the mTORC1 complex, increasing its kinase activity. Finally, AKT regulates FOXO3 phosphorylation, sequestering it in the cytosol in an inactive state.


Torsion of spermatocele and aplasia of the vas deferens. A case report.
Torsion of a spermatocele combined with aplasia of the vas deferens is described. The purpose of this case report is that this rare condition should not be omitted from the differential diagnosis of the acute scrotum in childhood. The authors also support that the term "spermatocele" could be used in the non semen producing age of childhood, based upon the non age-dependent pathologic criteria.


Simultaneous Overexpression of Integrated Genes by Copy Number Amplification of a Mini-Yeast Artificial Chromosome.
A copy number amplification system for yeast artificial chromosomes (YACs) was combined with simultaneous overexpression of genes integrated into a YAC. The chromosome VII (1,105 kb) was successfully split to 887 kb, 44 kb containing the element for copy number amplification, and a 184-kb split-YAC. The 44-kb split-mini YAC was amplified a maximum of 9-fold, and the activity of the reporter enzymes integrated into the split-mini YAC increased about 5-7-fold. These results demonstrate that the mini-YAC containing a targeted chromosome region can be readily amplified, and the specific genes in the mini-YAC could be overexpressed by increasing the copy number.


A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls with androgen excess.
Serine-threonine kinase STK11 catalyzes the AMP-activated protein kinase complex. We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy. We studied the effects of a single nucleotide polymorphism (SNP) (rs8111699) in STK11 on endocrine-metabolic and body composition indexes before and after 1 year of metformin in 85 hyperinsulinemic girls with androgen excess, representing a continuum from prepuberal girls with a combined history of low birth weight and precocious pubarche over to postmenarchial girls with hyperinsulinemic ovarian hyperandrogenism. Metformin was dosed at 425 mg/day in younger girls and 850 mg/day in older girls. STK11 rs8111699 was genotyped. Endocrine-metabolic features were assessed in the fasting state; body composition was estimated by absorptiometry. Genotype effects were similar in younger and older girls. At baseline, the mutated G allele in STK11 rs8111699 was associated with higher insulin and IGF-I levels (both P < 0.005). The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response. Such differences were found for 1-year changes in body composition, circulating insulin, IGF-I, free androgen index, and lipids (all P < 0.005). In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy.


Short-term exposure to air pollution and infant mortality: A systematic review and meta-analysis.
Infant mortality is a widely reported indicator of population health and a leading public health concern. In this systematic review and meta-analysis, we review the available literature for epidemiologic evidence of the association between short-term air pollution exposure and infant mortality. Relevant publications were identified through PubMed and Web of Science databases using comprehensive search terms and screened using predefined inclusion/exclusion criteria. We extracted data from included studies and applied a systematic rubric for evaluating study quality across domains including participant selection, outcome, exposure, confounding, analysis, selective reporting, sensitivity, and overall quality. We performed meta-analyses, using both fixed and random-effect methods, and estimated pooled odds ratios (ORs) and 95 % confidence intervals (95%CI) for pollutants (nitrogen dioxide (NO2), sulfur dioxide (SO2), coarse particulate matter (PM10), fine particulate matter (PM2.5), ozone (O3), carbon monoxide (CO)) and infant mortality, neonatal mortality, or postneonatal mortality. Our search returned 549 studies. We excluded 490 studies in the abstract screening phase and an additional 37 studies in the full text screening phase, leaving 22 studies for inclusion. Among these 22 studies, 14 included effect estimates for PM10, 13 for O3, 11 for both NO2 and CO, 8 for SO2, and 3 for PM2.5. We did not calculate a pooled OR for PM2.5 due to the limited number of studies available and demonstrated heterogeneity in the effect estimates. The pooled ORs (95%CI) with the greatest magnitudes were for a 10-ppb increase in SO2 or NO2 concentration in the days before death (1.07 [95%CI: 1.02, 1.12], 1.04 [95%CI: 1.01, 1.08], respectively). The pooled OR for PM10 was 1.02 (95%CI: 1.00, 1.03), and the pooled ORs for CO and O3 were 1.01 (95%CI: 1.00, 1.02) and 0.99 (95%CI: 0.97, 1.01). Increased exposure to SO2, NO2, PM10, or CO is associated with infant mortality across studies.


Sr1/2Ce5/14□1/7WO4: a new modulated ternary scheelite compound.
For the first time, a ternary tetragonal scheelite structure tungstate with strontium and cerium cations, (Sr,Ce)WO4, was synthesized. As much as 35% Ce could be inserted into the structure, leaving 1\over 7 of the (Sr,Ce) cation sites vacant. Partial ordering of Sr and Ce, with atomic displacements, were shown by high-resolution electron microscopy. Two-dimensional incommensurate modulations occur in this material, in small domains 20 nm in size. The band gap of this compound is significantly lower than the band gap of SrWO4 and this was related to the distortions of WO4 and (Sr,Ce)O8 polyhedra. The band gap value of 3.2 eV makes Sr1/2Ce5/14□1/7WO4 a promising candidate for violet luminescence.


Characteristics and outcome of patients with difficult weaning from mechanical ventilation: an 18 years' experience of a respiratory intermediate unit attached to a pulmonary department.
Respiratory dysfunction often persists in post intensive care unit (ICU) patients and intermediate care facilities have been established to ensure the continuous of appropriate care. The data of patients with difficult weaning from mechanical ventilation admitted to a respiratory intermediate unit (RIU) attached to a pulmonary department of a General Hospital, were retrospectively analyzed. Clinical characteristics, weaning from mechanical ventilation and tracheostomy, ICU readmission and RIU mortality were examined over a period of 18 years (1993- 2010) that was randomly divided into three six-year-periods. A total of 548 patients (age 56.7±17.9 years) [mean ± standard deviation (SD)], of whom 80% with tracheostomy in place and 37.6% with pressure ulcers, were examined. The ICU stay was 30.1±24.7 days (mean ± SD) and increased over time (p<0.05). Patients' baseline disorders were: chronic respiratory disease (41.3%), chronic cardiovascular diseases (10.6%), neuromuscular disease (22.8%) and miscellaneous (25.3%). The length of RIU stay (22.8±19.5 days) was constant over the examined periods but an increase in age and maintenance of tracheostomy were observed; 80% of patients were liberated from mechanical ventilation and 58.5% from tracheostomy, whereas the RIU mortality was 15%. In their vast majority patients with chronic respiratory failure, who were admitted to RIU,were weaned from mechanical ventilation, although in a substantial percentage the maintenance of tracheostomy was mandatory after discharge. Hippokratia 2015, 19 (1): 37-40.


Sequentially administrated of pemetrexed with icotinib/erlotinib in lung adenocarcinoma cell lines in vitro.
Combination of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) had been proved to be a potent anti-drug for the treatment of tumors. However, survival time was not extended for the patients with lung adenocarcinoma (AdC) compared with first-line chemotherapy. In the present study, we attempt to assess the optimal schedule of the combined administration of pemetrexed and icotinib/erlotinib in AdC cell lines. Human lung AdC cell lines with wild-type (A549), EGFR T790M (H1975) and activating EGFR mutation (HCC827) were applied in vitro to assess the differential efficacy of various sequential regimens on cell viability, cell apoptosis and cell cycle distribution. The results suggested that the antiproliferative effect of the sequence of pemetrexed followed by icotinib/erlotinib was more effective than that of icotinib/erlotinib followed by pemetrexed. Additionally, a reduction of G1 phase and increased S phase in sequence of pemetrexed followed by icotinib/erlotinib was also observed, promoting cell apoptosis. Thus, the sequential administration of pemetrexed followed by icotinib/erlotinib exerted a synergistic effect on HCC827 and H1975 cell lines compared with the reverse sequence. The sequential treatment of pemetrexed followed by icotinib/erlotinib has been demonstrated promising results. This treatment strategy warrants further confirmation in patients with advanced lung AdC.


Advancements in ferroptosis research and therapeutic strategies for alcoholic liver disease: a narrative review.
Ferroptosis is a novel mechanism of programmed cell death characterized by an iron overload-induced lipid peroxidation cascade. The incidence of alcoholic liver disease (ALD) is rising globally, contributing to markedly high morbidity and mortality. ALD pathogenesis is an intricate and continuously evolving process. Several basic and clinical investigations have established a correlation between ferroptosis and ALD initiation and progression. Additionally, anti-ferroptosis drugs have demonstrated effectiveness in ameliorating alcohol-induced liver injury. This review aims to provide an overview of recent advancements in ferroptosis research pertaining to ALD, encompassing imbalance of antioxidant systems, iron overload, autophagy, mitochondria, epigenetic changes, and prospective therapeutic drugs targeting ferroptosis. Our aim is to reveal the potential of ferroptosis-related diagnoses and therapeutic interventions for the treatment of ALD.


[Peptide drug cortexin inhibits brain caspase-8].
Cortexin, a drug containing hydrolyzed brain peptides, has long been used in clinics, but the mechanisms of its action remain obscure. We have hypothesized that cortexin-related neuroprotection is associated with the ability of the drug to inhibit brain proteases. Cortexin effectively inhibited brain caspase-8, while its effects on caspase-1, -3, -9, cathepsin B and calpain were much less pronounced or absent. In addition, we isolated a peptide fraction from cortexin holding all the inhibitory capacity of the original drug, but with a much more simple composition. Both cortexin and its fraction prevented neuronal damage in a culture model of glutamate-induced cell death. Neuroprotective effect of Cortexin may be mediated by inhibition of the initiator caspase-8 in the brain.


Congenital gastric teratoma with gastric perforation mimicking meconium peritonitis.
A case of congenital immature gastric teratoma along with spontaneous gastric perforation in a 1-day-old boy is presented. The clinical features are similar to those of meconium peritonitis. Coincidentally, the child had an arachnoid cyst at 25 months of age. To the best of the authors knowledge, this case of congenital immature gastric teratoma associated with gastric perforation mimicking meconium peritonitis, is the first description in the English-language literature.


On the Kirkwood-Buff inversion procedure.
A general approach is presented to express the Kirkwood-Buff integrals, the central component of the Kirkwood-Buff theory of solutions, in terms of thermodynamic properties of solution mixtures. A general expression valid for any number of components is provided in terms of matrix cofactors, while explicit expressions are given for three and four component mixtures. The corresponding symmetric ideal solution values are also presented for four and higher component mixtures.


Efficacy and Cost-Effectiveness of Anti-VEGF for Treating Diabetic Retinopathy in the Indian Population.
In the present study, we aimed to evaluate the efficacy, safety, and cost-effectiveness of the anti-vascular endothelial growth factor (anti-VEGF), namely ranibizumab (RBZ) or bevacizumab (BVZ), after either focal or grid or scatter laser photocoagulation, for the treatment of diabetic macular edema (DME) in the Indian population. Retrospective data were collected in the Regional Institute of Ophthalmology, Kolkata, India between January 2018 and June 2019. Seventy-seven eyes received 3 consecutive monthly intravitreal injections of RBZ (0.5 mg) and were followed by prompt laser photocoagulation (within 7-10 days after the third injection). Similarly, 51 eyes received 3 consecutive monthly intravitreal injections of BVZ (1.25 mg), an off-label drug, and were followed by prompt laser therapy. Safety assessments of the therapy, as well as surrogate markers of biochemical derangements related to diabetic retinopathy (DR), were also investigated at the end of 12 months. Seventy-seven subjects who were given a treatment of RBZ+laser therapy showed average 6.87±5.53 letters gain in their best-corrected visual acuity (BCVA) score, whereas the ones treated with off-label BVZ+ laser therapy demonstrated improvement in BCVA of an average 6.82±5.76 letters in "Early Treatment Diabetic Retinopathy Study" (ETDRS) chart. The study also highlights the cost-effectiveness of both RBZ+laser and BVZ+laser therapies for the treatment of DME in DR. The results demonstrated that a subject has to pay 20.951 times more cost (in INR) for RBZ+laser therapy compared to BVZ+laser therapy, to get an almost similar outcome. BVZ is found to be the more attractive option for treating DME in DR for its cost-friendliness over RBZ in terms of BCVA outcome, as well as the safety perspectives, at least for the economically backward population in developing countries, like India.


Evidence for angiotensin-stimulated proximal tubular fluid reabsorption in normotensive and hypertensive rats: effect of acute administration of captopril.
The effects of captopril on mean arterial blood pressure and proximal tubular fluid reabsorption (JV) were examined in anaesthetized normotensive rats and in the non-clipped kidneys of two-kidney, one-clip Goldblatt hypertensive rats. In the normotensive animals, captopril reduced arterial blood pressure from 121 +/- SD 9 to 106 +/- 10 mmHg and JV decreased from 3.78 +/- 0.45 to 2.57 +/- 0.58 X 10(-4) mm3 mm-2 s-1. Captopril had a greater effect on blood pressure in the hypertensive animals (172 +/- 17 reduced to 133 +/- 23 mmHg) although the decrease in JV from 3.62 +/- 0.12 to 2.40 +/- 0.40 was similar to that observed in normotensive animals. These results provide evidence that, in the anaesthetized rat, angiotensin II contributes to the maintenance of the rate of proximal fluid reabsorption. The magnitude of the angiotensin-stimulated component of proximal fluid absorption is similar in normotensive and two-kidney, one-clip Goldblatt hypertensive rats.


Cytokine-Induced Killer Cells As Pharmacological Tools for Cancer Immunotherapy.
Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3+CD56+ natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor. Furthermore, we briefly sum up the clinical trials on CIK cells and compare the effect of clinical CIK therapy with other immunotherapies. Finally, further research is needed to clarify the pharmacological mechanism of CIK and provide evidence to formulate uniform culturing criteria for CIK expansion.


Leukotriene receptor antagonism prevents lung protein leakage and hypoxaemia in a septic cat model.
Products of the arachidonic acid cascade have been found to play an important role in the pathophysiology in experimental shock and in ARDS. The effect of cysteinyl-leukotriene (cLT) blockade on the development of respiratory failure during septic shock was examined. Ventilated cats received an infusion of Escherichia coli bacteria. Pretreatment was given with diethylcarbamazine (DEC), a leukotriene synthetase inhibitor, or a new potent cLT receptor antagonist, ICI 198,615. With a gamma camera, the distributions of plasmatransferrin radiolabelled with indium-113m chloride (113mIn) and erythrocytes radiolabelled with technetium-99m (99mTc) were measured over the lungs. A normalized slope index (NSI) reflecting protein leakage, based on the transferrin extravasation, was calculated. In the nonseptic control group (n = 7) NSI was 4.4 x 10(-4) +/- 0.7 x 10(-4).min-1 (mean +/- SEM). Unpretreated septic animals (n = 7) showed a protein leakage after bacterial infusion, with a NSI of 34 +/- 3.5 x 10(-4).min-1. Pretreatment with DEC (n = 6) significantly reduced NSI to 16 +/- 1.5 x 10(-4).min-1. In the group pretreated with ICI 198,615 (n = 8), NSI was 9 +/- 1.2 x 10(-4).min-1. Arterial oxygen tension (PaO2) remained at baseline level of 20 +/- 1.0 kPa during the experimental period in both the nonseptic control group and the ICI 198,615 pretreated group. In the unpretreated septic group, PaO2 fell progressively from a preseptic value of 21 +/- 0.9 to 12 +/- 1.5 kPa after 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)


Argon laser therapy of verrucous nevi.
In one patient afflicted with a systemic verrucous nevus, a marked improvement was obtained by repeated treatments with an argon laser. In two patients it was possible to remove localized verrucous nevus completely. There was no recurrence in the follow-up of 8 and 14 months, respectively.


Changes of post-transcriptional modification of wye base in tumor-specific tRNAPhe.
Nucleotide sequences of normal mouse liver tRNAPhe and tumor-specific tRNAPhes isolated from Ehrlich ascites tumor and neuroblastoma cells were examined by post-labeling techniques. The results showed that their sequences are identical, except for changes in post-transcriptional modifications that are located in the anticodon region. Normal mouse liver tRNAPhe contained Cm32, Gm34 and YOH37. On the other hand, tumor-specific tRNAPhes were found in one of two possible configurations: 1) Cm32, Gm34 and Y*OH37 (under-modified YOH) or 2) C32, G34 and m1G37. The ratio of the two forms of tRNAPhes differed in different tumor cells; Ehrlich ascites tumor tRNAPhe had mainly Y*OH-containing tRNAPhe whereas neuroblastoma tRNAPhe has predominantly m1G-containing tRNAPhe. It was concluded that tumor-specific tRNAPhes are products of different extents of modification, rather than of new tRNA transcription.


Listening and Hearing: A Voice Hearer's Invitation into Relationship.
Although historically overlooked, empirical links between trauma and psychosis have received growing attention over the past decade. Increasingly, clinical researchers have also zeroed in on the role that distressing or traumatic life events play in the psychosocial formation and maintenance of psychosis. This paper re-locates anomalous experiences in their human contexts, and asks that clinicians and researchers engage with these contexts. The author shares a first person account of her experience changing her relationships with dominance in order to reclaim and accept her human being-ness, a reorientation supported by her involvement in the world hearing voices network movement and community. She calls for mental health systems, providers, and researchers to collaborate with the persons at the center of their work-to dare to listen, hear, and connect for mutual learning, healing, and wholeness. The article concludes with recommendations and a rallying call for services to be made more inclusive and to re-center in meaningful collaboration with people with lived experience. More comprehensive, meaningful, and accountable practices can be co-created when people are met equally as human subjects, both responsible and accountable for change.


Tissue distribution, molecular profile, and shedding of a cytoplasmic antigen identified by the monoclonal antibody 465.12S to human melanoma cells.
The mouse immunoglobulin G2 monoclonal antibody (MoAb) 465.12S reacts with a cytoplasmic antigen present in human melanoma cells but not detectable in melanocytes. Indirect immunofluorescent staining of a large number of surgically removed normal adult and fetal tissues with the MoAb 465.12S detected the cytoplasmic antigen in epithelial cells from several organs. The intensity of staining was greater in adult tissues than in the corresponding fetal tissues. Furthermore, the MoAb 465.12S stained nearly all of the surgically removed tumors tested but did not stain many of the normal tissues from which they originated. In almost all cases, the intensity and frequency of staining wa greater for tumor cells than for corresponding normal tissues. From cultured carcinoma and melanoma cells, the MoAb 465.12S immunoprecipitated four glycopolypeptides with molecular weights of 94,000, 75,000, 70,000, and 25,000. Incorporation of 3H-labeled sugars into the various components of the cytoplasmic antigen revealed that the M.W. 75,000 component was unusual in that it contained only glucosamine and mannose. The antigenic determinant defined by the MoAb 465.12S appears to be protein rather than carbohydrate in nature since it is heat sensitive and is expressed on the antigens synthesized by cells in presence of tunicamycin. Analysis of the spent culture medium of carcinoma and melanoma cell lines revealed that the cytoplasmic antigen is readily shed by these cells and consists of a major M.W. 94,000 and a minor M.W. 72,000 component. Treatment of cultured melanoma cells with the antibiotic tunicamycin showed that glycosylation of the cytoplasmic antigen is required for its shedding and/or stability in the spent culture medium.


Identification of class I genes in cartilaginous fish, the most ancient group of vertebrates displaying an adaptive immune response.
Sharks are members of the most primitive class of vertebrates (Chondrichthyes) shown to have an adaptive immune system. Suprisingly, however, class I genes have not been identified unambiguously in this taxon, and absence of class I loci or a failure to express class I genes might explain some of the relatively "weak" adaptive immune responses documented in cartilaginous fish. We report here the isolation of three unique cDNA clones from two different species of sharks that encode bona fide class I proteins. These clones exhibit different sequence and expression profiles indicating that they are likely to represent both classical and nonclassical class I lineages. In addition, our preliminary analysis suggests that there may be transfer of gene segments among shark class I genes over evolutionary time. The cloning of shark class I genes completes the identification of molecules that define the adaptive immune system (including Ig, TCR, and MHC class II proteins) in this taxon. Thus, simple models invoking a total absence of certain molecular hallmarks of the immune system to account for poor immune responsiveness in cartilaginous fish should be abandoned.


Evaluation of Unintended Social and Economic Consequences of an Unplanned School Closure in Rural Illinois.
School closure is one of the primary measures considered during severe influenza pandemics and other emergencies. However, prolonged school closures may cause unintended adverse consequences to schools, students, and their families. A better understanding of these consequences will inform prepandemic planning, and help public health and education authorities in making informed decisions when considering school closures. We conducted a household survey and interviewed school officials following an 8-day long closure of a school district in rural Illinois. We described household responses regarding difficulties of school closure, and summarized main themes from school official interviews. A total of 208 (27%) household surveys were completed and returned. This school closure caused difficulties to 36 (17%) households; uncertain duration of closure, childcare arrangements, and lost pay were the most often reported difficulties. Having 1 adult in the household losing pay and household income below $25,000 were significantly associated with overall difficulty during this school closure. Concern about student health and safety was the most frequent theme in school administrator interviews. Whereas the majority of responding households did not report difficulties during this school closure, households with 1 adult losing pay during the closure reported incurring additional expenses for childcare.


[Immunohistochemical detection of p21ras, c-myc and p53 oncoproteins in hepatocellular carcinoma and in non-neoplastic liver tissue].
Genetic and epigenetic alterations have been described in animal hepatocarcinogenesis models but need to be studied in human being. To assess the immunoreactivity of p21ras, c-myc and p53 oncoproteins in hepatocellular carcinoma and non neoplastic tissue. Association of the immunoreactivity of these markers with histological grades and patterns, hepatitis B and C were additionally studied. Detection of oncoproteins p21ras, c-myc and p53 was performed immunohistochemically in hepatocellular carcinoma (47 cases) and surrounding non neoplastic liver tissue (40 cases). Oncoproteins p21ras, c-myc and p53 were detected in 44,7%, 53,2% and 36,2% of the hepatocellular carcinoma cases, respectively. The p21ras and c-myc immunoreactivity has shown a significant association. However there was no association of p21ras, c-myc and p53 detection with hepatitis B and C virus infections, histological grades and patterns. The same significant association between p21ras and c-myc was observed in non-neoplastic tissue with cirrhosis when compared with tissue without it. The p53 immunoreactivity was negative in all non-neoplastic liver tissue samples. The immunoreactivity detection of p21ras, c-myc and p53 corroborates previous evidence of their detection in hepatocellular carcinoma that suggest the participation of these proteins in human hepatocarcinogenesis. The significant association between p21ras and c-myc oncoproteins in hepatocellular carcinoma and in cirrhosis can point to an interaction between them mainly, in hepatocarcinogenesis that occurs through cirrhosis.


A more rapid, sensitive, and specific HPLC-MS/MS method for nifedipine analysis in human plasma and application to a pharmacokinetic study.
A more rapid, sensitive and specific high-performance liquid chromatography coupled to -tandem mass spectrometry (HPLC-MS/MS) was developed and validated for the quantification of nifedipine in human plasma, and applied to the pharmacokinetic study of nifedipine in Chinese healthy volunteers. Nifedipine and internal standard (IS) acetaminophen in plasma were extracted with ethyl acetate, separated on a C18 (150 mm×4.6 mm, 5 µm) reversed-phase column, eluted with acetonitrile mixed with 5 mM ammonium acetate solution (pH=6.62) (60:40, v/v), ionized by negative ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor→product ions of m/z 354.1→222.2 for nifedipine and 150.1→107.1 for the IS. A single oral dose of 20 mg nifedipine sustained release tablets and blood samples (4 mL) was collected before and 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, and 36 h after administration. The main pharmacokinetic parameters of nifedipine, as Tmax, t1/2α, t1/2β, t1/2z, Cmax, AUC0~36, AUC0~∞ were 2.80±0.50 h, 6.78±2.52 h, 6.82±2.53 h, 6.69±2.22 h, 76.69±19.51 (ng/mL), 546.49±162.28 (ng · h/mL) and 564.05±176.74 (ng · h/mL), respectively. The calibration curve was linear over the concentration range of 0.17-102 ng/mL (r2>0.99, n=5) with a lower limit of quantification (LLOQ) of 0.17 ng/mL. The intra- and inter-day precision was less than 15% for all quality control samples at concentrations of 0.42, 6.53 and 81.60 ng/mL and the accuracy (relative error, RE) was - 3.92% to 7.31% at 3 quality control levels. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision and stabilities were validated, and can fulfill the requirement of pharmacokinetic study of nifedipine sustained release tablets in Chinese volunteers.


An evolutionarily conserved gene family encodes proton-selective ion channels.
Ion channels form the basis for cellular electrical signaling. Despite the scores of genetically identified ion channels selective for other monatomic ions, only one type of proton-selective ion channel has been found in eukaryotic cells. By comparative transcriptome analysis of mouse taste receptor cells, we identified Otopetrin1 (OTOP1), a protein required for development of gravity-sensing otoconia in the vestibular system, as forming a proton-selective ion channel. We found that murine OTOP1 is enriched in acid-detecting taste receptor cells and is required for their zinc-sensitive proton conductance. Two related murine genes, Otop2 and Otop3, and a Drosophila ortholog also encode proton channels. Evolutionary conservation of the gene family and its widespread tissue distribution suggest a broad role for proton channels in physiology and pathophysiology.


[Relative functional changes in neutrophils in early period of acute lung injury in rabbit].
To explore the relationship of interleukin-8 (IL-8), adherence function of neutrophil (PMN) and acute lung injury (ALI). Eighteen male New Zealand rabbits were divided into two groups randomly: the control group (n=8) and the ALI group (n=10). The model of ALI was replicated by using intravenous lipopolysaccharide (LPS) in the rabbits of group ALI. Blood pressure, heart rate, blood gas analysis, hemogram, CD11b expression intensity on the surface of PMN, concentration of serum IL-8 and malondialdehyde (MDA) were measured at each time point. Specimens for pathology were obtained at the end of experiment. In group ALI, blood pressure, heart rate and pH declined obviously. PMN count was lowered obviously at 3 hours and increased at 6 hours to some extent. CD11b expression intensity on the surface of PMN, the concentration of serum IL-8 and MDA were increased progressively (all P<0.05). The main changes in the microscopic examination were inflammatory granulocyte infiltration, disseminated thickening of alveolar septa and focal hemorrhages. There were significant correlations between CD11b and IL-8 (r2=0.813, Y=26.729X), and between CD11b and the grades of pathological changes at 6 hours after intravenous LPS (r2=0.771, Y=0.011 02X+5.292). LPS could induce the release of large amount of IL-8, and it activates the expression of CD11b on the surface of PMN, which shows high degree of correlation with IL-8 and the degree of pathological changes in the lung. Therefore, both of them could serve as sensitive indexes for the diagnosis of ALI.


Chronic non-specific diarrhoea in childhood: how often is it iatrogenic?
Epidemiological data, the appropriateness of the medical approach, the effectiveness of unrestricted diet and the subsequent course of chronic non-specific diarrhoea (CNSD) were evaluated in 20 children, mean age at diagnosis 4.7 y, and mean duration of diarrhoea 24 months. A mean of 2.4 previous hospital admissions and a mean of 2.5 diagnoses other than CNSD were recorded per child before admission. On admission, 14/20 were following an elimination diet and 8/20 had an inadequate caloric intake; 16/20 had a weight/height ratio below the 50th percentile. In all cases a normal diet prescribed during hospitalization improved the diarrhoea and increased weight. A telephone interview performed 5.6 y after discharge revealed that in 10/20 of the cases, the parents were disappointed with the unrestricted diet prescribed during hospitalization. Nevertheless they reported that CNSD stopped spontaneously in a mean time of 1.7 y.


Ureteroscopic management of upper urinary tract urothelial malignancies.
The endoscope has made the transition from diagnostic tool to therapeutic aid in the upper urinary tract in recent years. Because of success using the ureteropyeloscope in the treatment of patients with upper tract stones and strictures, investigators are now looking at endoscopic management of urothelial malignancies above the bladder.


Long-time and unitary properties of semiclassical initial value representations.
We numerically compare the semiclassical "frozen Gaussian" Herman-Kluk propagator [Chem. Phys. 91, 27 (1984)] and the "thawed Gaussian" propagator put forward recently by Baranger et al. [J. Phys. A 34, 7227 (2001)] by studying the quantum dynamics in some nonlinear one-dimensional potentials. The reasons for the lack of long-time accuracy and norm conservation in the latter method are uncovered. We amend the thawed Gaussian propagator with a global harmonic approximation for the stability of the trajectories and demonstrate that this revised propagator is a true alternative to the Herman-Kluk propagator with similar accuracy.


New records and descriptions of Ichneumonidae (Hymenoptera) from Mexico.
Based on a large quantity ichneumonid material collected mainly from the Mexican states of Veracruz and Quintana Roo, faunistic records of 79 species belonging to subfamilies Acaenitinae, Banchinae, Cryptinae, Cylloceriinae, Labeninae, Lycorininae, Microleptinae, Pimplinae, Tersilochinae, and Tryphoninae are provided. Three species are described as new to science: Latosculum ortegai Kasparyan Khalaim, sp. nov. (Cryptinae), Eusterinx madorae Khalaim Kasparyan, sp. nov. (Microleptinae) and Neotheronia veracruzana Khalaim, sp. nov. (Pimplinae). Two genera, Nipponaetes Uchida (Cryptinae) and Meggoleus Townes (Tersilochinae), and six species, Nipponaetes hansoni (Gauld) (Cryptinae), Lycorina moralesi Gauld (Lycorininae), Neotheronia murilloi Gauld (Pimplinae), Meggoleus pampahermosensis Alvarado (Tersilochinae), Phytodietus moragai Gauld, and Zagryphys zulaya Gauld (Tryphoninae), are first records from Mexico. Females of three species, Cestrus tenuiventris (Cresson), Mallochia macula Kasparyan Ruíz-Cancino (Cryptinae), and Phytodietus moragai Gauld (Tryphoninae), are recorded and described for the first time.


Honey Bees' Behavior Is Impaired by Chronic Exposure to the Neonicotinoid Thiacloprid in the Field.
The decline of pollinators worldwide is of growing concern and has been related to the use of plant-protecting chemicals. Most studies have focused on three neonicotinoid insecticides (clothianidin, imidacloprid, and thiamethoxam) currently subject to a moratorium in the EU. Here, we focus on thiacloprid, a widely used cyano-substituted neonicotinoid thought to be less toxic to honey bees and of which use has increased in the last years. Honey bees (Apis mellifera carnica) were exposed chronically to thiacloprid in the field for several weeks at a sublethal concentration. Foraging behavior, homing success, navigation performance, and social communication were impaired, and thiacloprid residue levels increased both in the foragers and the nest mates over time. The effects observed in the field were not due to a repellent taste of the substance. For the first time, we present the necessary data for the risk evaluation of thiacloprid taken up chronically by honey bees in field conditions.


Structure of the vitread face of the monkey optic disc (Macaca mulatta). SEM on frozen resin-cracked optic nerveheads supplemented by TEM and immunohistochemistry.
The authors applied frozen resin cracking after hexamethyldisilazane (HMDS) desiccation on the monkey optic disc region. The cracked face through the central part of the optic disc showed that the inner limiting membrane of the retina continued into the limiting membrane of Elschnig, and this, in turn, continued into the central meniscus of Kuhnt. At the disc margin the membrane was about 70 nm in thickness, due to a large fibrillar component. Elschnig's membrane was about 50 nm in thickness and was composed of both fibrils and flocculent material. The membrane covering the central meniscus of Kuhnt was about 20 nm in thickness. The number of fibrils here was very low, and the membrane consisted of flocculent material. The positive immunohistochemical stainings for GFA and vimentin of Elschnig's membrane and Kuhnt's meniscus were noteworthy. The positive staining disappeared when the membrane continued into the inner limiting membrane of the retina, supporting the different structural composition.


Scedosporium inflatum infection in immunocompromised haematological patients.
We report four cases of Scedosporium inflatum (S. inflatum) infection in severely immunocompromised haematological patients. Six well-documented cases of S. inflatum disseminated infection in haematological patients have been reported: four in Australia and two in Spain. Their clinical and pathological characteristics are heterogenous, particularly in the Australian cases. However, the clinical and pathological profile emerging from our and other Spanish cases is homogenous and very similar to the clinico-pathological spectrum of other disseminated mycoses, including Aspergillus and S. apiospermum. The optimal treatment of S. inflatum infection is unknown and the outcome in haematological patients is very poor. Eight patients died despite systemic antifungal treatment.


Terminological subset of the International Classification for Nursing Practice for patients hospitalized due to burns.
To develop a proposal of a terminological subset of the International Classification for Nursing Practice for burned patients. This is a methodological study following the steps: identification of clinical findings; mapping of terms; construction of statements of diagnoses/results and nursing interventions; content validation of statements; and structuring of the subset with the theoretical model of Basic Human Needs. Content validation was performed by 26 specialist nurses, through the Content Validity Index, with statements ≥ 0.80 being considered validated. A total of 36 diagnoses/results and 119 interventions were validated. Among these, the ones with the highest index were: Respiratory System Function, Impaired/Respiratory System Function, Effective; Volume of Fluids, Impaired/Volume of Fluids, Effective; Burn Wound/Wound Healing, Effective; Pain, Acute/Pain, Absent, and as interventions: To Monitor Vital Signs; to Monitor Fluid Balance; to Treat Skin Condition; to Assess Response to Pain Management (Control). The validated statements depict the burned people basic human needs, with the psychobiological ones being the most prevalent.


Mechanisms of fast and stringent search in homologous pairing of double-stranded DNA.
Self-organization in the cell relies on the rapid and specific binding of molecules to their cognate targets. Correct bindings must be stable enough to promote the desired function even in the crowded and fluctuating cellular environment. In systems with many nearly matched targets, rapid and stringent formation of stable products is challenging. Mechanisms that overcome this challenge have been previously proposed, including separating the process into multiple stages; however, how particular in vivo systems overcome the challenge remains unclear. Here we consider a kinetic system, inspired by homology dependent pairing between double stranded DNA in bacteria. By considering a simplified tractable model, we identify different homology testing stages that naturally occur in the system. In particular, we first model dsDNA molecules as short rigid rods containing periodically spaced binding sites. The interaction begins when the centers of two rods collide at a random angle. For most collision angles, the interaction energy is weak because only a few binding sites near the collision point contribute significantly to the binding energy. We show that most incorrect pairings are rapidly rejected at this stage. In rare cases, the two rods enter a second stage by rotating into parallel alignment. While rotation increases the stability of matched and nearly matched pairings, subsequent rotational fluctuations reduce kinetic trapping. Finally, in vivo chromosome are much longer than the persistence length of dsDNA, so we extended the model to include multiple parallel collisions between long dsDNA molecules, and find that those additional interactions can greatly accelerate the searching.


Underperception of Naps in Older Adults Referred for a Sleep Assessment: An Insomnia Trait and a Cognitive Problem?
To examine the frequency and determinants of underperception of naps in older adults referred for a sleep assessment. Prospective study. Outpatient geriatric sleep clinic. Individuals aged 60 and older referred for insomnia complaints or suspected sleep apnea (N = 135). Tests included clinical interview, sleepiness scale, anxiety and depression scale, Insomnia Severity Index (ISI), Mini-Mental State Examination (MMSE), and overnight polysomnography, followed by multiple sleep latency tests. At the end of each of four nap opportunities, participants answered whether they had slept during the test. Nap underperception was defined as two or more unperceived naps. Of the 105 participants who napped at least twice, 42 (40%) did not perceive at least two naps. These participants had lower MMSE scores (P = .01) and were more likely to be taking benzodiazepines (P = .008) than the 63 participants who did not underperceive their naps but had similar demographic characteristics, sleep diagnoses, depression and anxiety scores, and polysomnography measures. Both groups had similarly short mean daytime sleep latencies (9.7 ± 4.5 minutes and 9.8 ± 3.7 minutes), but participants who underperceived their naps scored lower on the Epworth Sleepiness Scale (5.6 ± 4.0, vs 9.6 ± 4.8, P < .001). An ISI of 11 or greater, a MMSE score of 26 or less, and a sleepiness score of 8 or less were each independently associated with underperception of naps. The combination of these three factors yielded a positive predictive value of 93% and a negative predictive value of 71% for nap underperception. Older adults referred for sleep consultation with cognitive impairment and greater insomnia symptoms frequently underperceive naps, leading them to underestimate their level of sleepiness. In such cases, objective measures of daytime sleepiness would be better than the Epworth Sleepiness Scale.


Nephrotic syndrom with heart disease: a reappraisal.
The evidence that heart failure alone may cause a nephrotic syndrome is inconclusive. Mercurial diuretics, which have also been implicated as a cause of the nephrotic syndrome, had been given in 23 of the 24 well-documented cases.Two cases of heart disease and nephrotic syndrome are described. Glomerular lesions were minimal on light microscopy, but thickening of the glomerular tuft basement membrane and partial fusion of the epithelial cell foot processes were apparent on elecronmicroscopy. The response to prednisone was such as to justify a trial of corticosteroid therapy in such cases despite the presence of cardiac disease.


Hyperbaric oxygen therapy: a meeting place for medicine and dentistry.
The hyperbaric medicine facility at Hennepin County Medical Center has been serving patients from throughout the region for more than 40 years. Some of these patients have head and neck cancer and are suffering delayed complications of radiation therapy. Such patients are often referred by dentists, oral surgeons, and otolaryngologists. This article summarizes outcomes for patients who have received hyperbaric oxygen therapy for 3 conditions: soft-tissue radiation injury before undergoing dental extractions, osteoradionecrosis, and soft-tissue radiation injury prior to receiving dental implants in the irradiated area.


The influence of crowding on clinical practice in the emergency department.
This study aimed to clarify the association between the crowding and clinical practice in the emergency department (ED). This 1-year retrospective cohort study conducted in two EDs in Taiwan included 70,222 adult non-trauma visits during the day shift between July 1, 2011, and June 30, 2012. The ED occupancy status, determined by the number of patients staying during their time of visit, was used to measure crowding, grouped into four quartiles, and analyzed in reference to the clinical practice. The clinical practices included decision-making time, patient length of stay, patient disposition, and use of laboratory examinations and computed tomography (CT). The four quartiles of occupancy statuses determined by the number of patients staying during their time of visit were <24, 24-39, 39-62, and >62. Comparing >62 and <24 ED occupancy statuses, the physicians' decision-making time and patients' length of stay increased by 0.3h and 1.1h, respectively. The percentage of patients discharged from the ED decreased by 15.5% as the ED observation, general ward, and intensive care unit admissions increased by 10.9%, 4%, and 0.7%, respectively. CT and laboratory examination slightly increased in the fourth quartile of ED occupancy. Overcrowding in the ED might increase physicians' decision-making time and patients' length of stay, and more patients could be admitted to observation units or an inpatient department. The use of CT and laboratory examinations would also increase. All of these could lead more patients to stay in the ED.


Understanding Protein Structure Deformation on the Surface of Gold Nanoparticles of Varying Size.
Gold nanoparticles (AuNPs) have been of recent interest due to their unique optical properties and their biocompatibility. Biomolecules spontaneously adsorb to their surface, a trait that could potentially be exploited for drug targeting. Currently, it is unclear whether protein-AuNP interactions at the nanoparticle surface are dependent on nanoparticle size. In this work, we investigate whether varying surface curvature can induce protein unfolding and multilayer binding in citrate-coated AuNPs of various sizes. A recently developed NMR-based approach was utilized to determine the adsorption capacity, and protein NMR spectra were compared to determine whether nanoparticle size influences protein interactions at the surface. In addition, transmission electron microscopy (TEM) and dynamic light scattering (DLS) were employed to corroborate the NMR studies. Over a broad range of AuNP sizes (14-86 nm), we show that adsorption capacity can be predicted by assuming that proteins are compact and globular on the nanoparticle surface. Additionally, roughly one layer of proteins is adsorbed regardless of AuNP size. Our results hold for two proteins of significantly different sizes, GB3 (6 kDa) and bovine carbonic anhydrase (BCA, 29 kDa). However, the unstable drkN SH3 domain (ΔḠ0 ≈ 0, 7 kDa) does not appear to follow the same trend seen for stable, globular proteins. This observation suggests that unstable proteins can deform significantly when bound to AuNP surfaces. Taken together, the results of this work can be used to improve our knowledge of the mechanism of protein-AuNP interactions to optimize their use in the biomedical field.


Structure and replication of chromosomes in competent cells of Bacillus subtilis.
Competent cultures of Bacillus subtilis 168 were fractionated on gradients of Renografin-76 to obtain a population enriched for competent cells. The cells in this fraction contained two nuclear bodies. The competent cell fraction synthesized deoxyribonucleic acid and ribonucleic acid at reduced rates compared to the noncompetent cell fraction and appeared to divide synchronously upon incubation. The state of the chromosome in competent cells was determined by density transfer experiments and marker frequency analyses. The results are consistent with a competent cell possessing two, or a multiple of two, chromosomes, one complete and the other partially duplicated. During subsequent growth the partially completed chromosome replicates preferentially.


Artificial cardiac pacing: 2. follow-up and complications.
Following insertion or implantation of an artificial cardiac pacemaker, both physician and patient are involved in aftercare to monitor the patient's cardiac status, the condition of the implantation site, and the function of the pacemaker. Among the complications that may occur are pacemaker malfunction and perforation of the ventricles. The physician and patient must also be alert to the possibility of electrical interference and to the physiologic factors that can modify pacemaker function.


THE GROWTH AND SIZE DISTRIBUTION OF CURRENT YEAR CLASS LOLIGO PEALEI.
1. This paper reports estimates of the growth rate and size distribution of current year class L. pealei based upon the population statistics of daytime, otter trawl collections in Menemsha Bight during the second half of 1967. 2. The selectivity of a #35 otter trawl with a 1.25-inch mesh (3.2-cm.) stretched measure cod end liner was estimated by a 50% retention of L. pealei with a dorsal mantle length of approximately 3.7 cm. 3. The current year class, summed older year classes and individual older year classes of L. pealei were found to have lognormal size-frequency distributions. 4. The current year class could readily be separated from the older year classes by the use of Cassie's method on lognormal probability paper. 5. The growth rate of a median individual in the current year class of 1967 was found to be 1.8 cm. dorsal mantle length per month for the first four months past hatching. 6. Approximately one-half of the one-year-old L. pealei did not mature sexually before the second fall migration. None of the current year class L. pealei matured before the first fall migration. 7. The results indicate that L. pealei egg deposition is isolated in time and location, and repeated throughout the Vineyard Sound area from at least June through September.


The relationship between inflammation, dyslipidemia and physical exercise: from the epidemiological to molecular approach.
Dyslipidemia and inflammation are frequently found in some diseases, such as obesity, type 2 diabetes mellitus, and cancer cachexia. Recent literature has identified that lipids have a pivotal role in the activation of inflammatory pathways, increasing the production of inflammatory cytokines, mainly tumor necrosis factor alpha, interleukin 6 and 1β. On the other hand, cytokines can promote disruption of lipid metabolism, in special cholesterol reverse transport, which is linked to development of atherosclerosis. With this in mind, acute and chronic exercise trainings have been pointed as important tools to counteract both dyslipidemia symptoms and systemic inflammation. Moreover, physical activity has been recommended in the prevention/treatment of the above mentioned outcomes by important health organizations around the world, mainly because it costs less and generates fewer side effects than isolated medicine. Despite the well-documented capacity of acute and chronic exercise training to counteract sustained disease-related immunometabolism, we have chosen to take a look from a current perspective in molecular pathways and in the field of epidemiology. The aim of the present review was therefore to discuss the results of dyslipidemia and inflammatory conditions with acute and chronic exercise training, which underlies the field of molecular pathways and epidemiology. The mechanisms underlying the response to the treatment are considered.


Intra-aortic balloon pumping in the elderly: percutaneous versus surgical catheter insertion.
The feasibility and safety of percutaneous versus intra-aortic balloon pumping (IABP) in the elderly were evaluated in 45 patients who were over 65 years of age (range 65-79). All the patients required counterpulsation for complicated acute myocardial infarction. IABP insertion was attempted by the surgical technique in 22 patients, while the percutaneous approach was performed in 23. A consistent improvement in the incidence rate of successful insertion was attained with the use of the percutaneous technique as compared with the surgical one (91.3% v 59.1%, P is less than 0.05). Furthermore, no major complication was observed with the percutaneous catheter, while a 9.1% (2/22) incidence rate of serious complications was reported with the surgical technique. Thus, percutaneous IABP substantially decreased the unsuccessful insertions and the risk of severe complications in old patients, despite presumably severe aorto-iliac disease. No specifically age-related technical problem seems, therefore, to limit the applicability of intra-aortic counterpulsation to elderly patients, when percutaneous IABP is employed.


Simple blood tests can predict compensated liver cirrhosis in patients with chronic hepatitis C.
Twenty to fifty percent of patients with chronic hepatitis C virus infection will insidiously progress to cirrhosis after 10-20 years' follow-up. The aim of this study is to retrospectively evaluate the role of simple non-invasive blood tests in detecting the presence of compensated liver cirrhosis in Chinese patients with chronic hepatitis C. One hundred and eleven biopsy-proven chronic hepatitis C patients were enrolled, 23 (20.7%) patients showed cirrhosis with class A in Child-Pugh's classification and were all asymptomatic. Liver biochemistry, complete blood count, and serum N-terminal propeptide of type III procollagen were determined and then compared between chronic hepatitis C patients with compensated cirrhosis and without cirrhosis. Multivariate logistic regression analysis was used to predict factors associated with compensated cirrhosis. Multivariate logistic regression analysis showed platelet count < or = 140,000/mm3 (odds ratio: 23.44, P < 0.001), globulin/albumin ratio > or = 1 (odds ratio: 31.47, P = 0.008), and AST/ALT ratio > or = (odds ratio: 6.58, P = 0.035) were significant predictors associated with hepatitis C virus-related compensated cirrhosis. Platelet count < or = 140,000/mm3 had 83% sensitivity and 85% specificity in detecting liver cirrhosis. Globulin/albumin ratio > or = 1 had 43% sensitivity, 98% specificity and AST/ALT ratio > or = 1 had 39% sensitivity, 92% specificity in detecting liver cirrhosis. Combined tests with AST/ALT > or = 1 and globulin/albumin > or = 1, platelet count < or = 140,000/mm3 and globulin/albumin > or = 1 had 100% specificity, 100% positive predictive value but lower sensitivity (22% and 39% respectively), lower negative predictive value (83% and 86%, respectively) in detecting hepatitis C virus-related compensated liver cirrhosis. Simple blood tests with platelet count < or = 140,000/mm3, globulin/albumin ratio > or = 1, and AST/ALT ratio > or = 1 can indicate liver cirrhosis in follow-up patients with chronic hepatitis C.


Functional, thermal, and antimicrobial properties of soluble soybean polysaccharide biocomposites reinforced by nano TiO2.
This study describes a new polysaccharide-based bionanocomposite developed through solvent casting. Different concentrations (i.e., 0%, 1%, 3%, and 5% (w/w)) of nano titanium dioxide (TiO2-N) were incorporated into soluble soybean polysaccharide (SSPS), and the functional properties of the resultant SSPS films were estimated. Incorporation of TiO2-N into the SSPS matrix decreased water vapor permeability from 7.41 to 4.44 × (10(-11)gm(-1) s(-1) Pa(-1)) and oxygen permeability from 202 to 98 (cm(3)μmm(-2) d(-1) atm(-1)). Moisture content also decreased, the glass transition temperature increased, and the mechanical properties and heat seal strength of the SSPS films improved. SSPS bionanocomposite films showed excellent antimicrobial activity against Escherichia coli and Staphylococcus aureus. In summary, TiO2-N shows potential use as a filler in SSPS-based films for the food and non-food industries.