Determination of bifonazole and identification of its photocatalytic degradation products using UPLC-MS/MS.
The main goal of the presented work was to investigate the effect of ZnO or/and TiO2 on the stability of bifonazole in solutions under UVA irradiation. To this end, a simple and reproducible UPLC method for the determination of bifonazole in the presence of its photocatalytic degradation products was developed. Linearity was studied in the range of 0.0046-0.15 mg mL-1 with a determination coefficient of 0.9996. Bifonazole underwent a photocatalytic degradation process under the experimental conditions used. Comparative studies showed that combination of TiO2 /ZnO (1:1 w/w) was a more effective catalyst than TiO2 or ZnO with a degradation rate of up to 67.57% after 24 h of irradiation. Further, kinetic analyses indicated that the photocatalytic degradation of bifonazole in the mixture of TiO2 /ZnO can be described by a pseudo-first order reaction. Statistical comparison clearly indicated that the presence of TiO2 /ZnO also affected the stability of bifonazole from a cream preparation after 15 h of UVA exposure (p < 0.05). Ten photodegradation products of bifonazole were identified for the first time and their plausible fragmentation pathways, derived from MS/MS data, were proposed. The main pathway in the photocatalytic transformation of bifonazole in the presence of ZnO or/and TiO2 involves hydroxylation of the methanetriyl group and/or adjacent phenyl rings and cleavage of the imidazole moiety.


Shigella as a Food borne Pathogen.
Shigellosis is classically thought of as a waterborne disease; however, public health data suggest that foodborne outbreaks are a significant, if not the major cause of the disease in the United States. The role of Shigella as a foodborne pathogen is reviewed, including discussions of taxonomy, epidemiology, virulence factors, growth and survival in foods and model systems, and methods for detection/identification in food products.


Differences in the RNA binding sites of iron regulatory proteins and potential target diversity.
Posttranscriptional regulation of genes of mammalian iron metabolism is mediated by the interaction of iron regulatory proteins (IRPs) with RNA stem-loop sequence elements known as iron-responsive elements (IREs). There are two identified IRPs, IRP1 and IRP2, each of which binds consensus IREs present in eukaryotic transcripts with equal affinity. Site-directed mutagenesis of IRP1 and IRP2 reveals that, although the binding affinities for consensus IREs are indistinguishable, the contributions of arginine residues in the active-site cleft to the binding affinity are different in the two RNA binding sites. Furthermore, although each IRP binds the consensus IRE with high affinity, each IRP also binds a unique alternative ligand, which was identified in an in vitro systematic evolution of ligands by exponential enrichment procedure. Differences in the two binding sites may be important in the function of the IRE-IRP regulatory system.


Immunosuppression facilitates the reactivation of latent papillomavirus infections.
At mucosal sites, papillomavirus genomes can persist in the epithelial basal layer following immune-mediated regression. Subsequent T-cell depletion stimulates a 3- to 5-log increase in the viral copy number, to levels associated with productive infection. Reappearance of microlesions was rare within the short time frame of our experiments but was observed in one instance. Our studies provide direct evidence that immunosuppression can trigger the reactivation of latent papillomavirus genomes, as previously proposed in humans.


Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing.
We reported that interstitial collagenase is produced by keratinocytes at the edge of ulcers in pyogenic granuloma, and in this report, we assessed if production of this metalloproteinase is a common feature of the epidermal response in a variety of wounds. In all samples of chronic ulcers, regardless of etiology, and in incision wounds, collagenase mRNA, localized by in situ hybridization, was prominently expressed by basal keratinocytes bordering the sites of active re-epithelialization indicating that collagenolytic activity is a characteristic response of the epidermis to wounding. No expression of mRNAs for 72- and 92-kD gelatinases or matrilysin was seen in keratinocytes, and no signal for any metalloproteinase was detected in normal epidermis. Immunostaining for type IV collagen showed that collagenase-positive keratinocytes were not in contact with an intact basement membrane and, unlike normal keratinocytes, expressed alpha 5 beta 1 receptors. These observations suggest that cell-matrix interactions influence collagenase expression by epidermal cells. Indeed, as determined by ELISA, primary cultures of human keratinocytes grown on basement membrane proteins (Matrigel; Collaborative Research Inc., Bedford, MA) did not express significant levels of collagenase, whereas cells grown on type I collagen produced markedly increased levels. These results suggest that migrating keratinocytes actively involved in re-epithelialization acquire a collagenolytic phenotype upon contact with the dermal matrix.


The newborn infant's thermal environment in the delivery room when skin-to-skin care has to be interrupted.
Newborns are prone to hypothermia immediately following birth. Hypothermia is associated with increased morbidity and mortality rates. We sought to assess the thermal environment and metabolic costs associated with exposure to various situations in the delivery room when skin-to-skin care (SSC) has to be curtailed. Environmental variables (air temperature: Ta; relative humidity: RH; radiative temperature: Tr; and air convection velocity) were recorded during sequences reproducing SSC, in the maternity unit's various rooms ("passive environments") and in incubators ("active environments"). Analytical calorimetry was then used to calculate the body heat loss (BHL) from these data. The analysis of 1280 measurements of Ta, RH, Tr, and air convection velocity in SSC, passive and active environments revealed that (i) the thermohygrometric environment during SSC was optimal (Ta: 32.7 ± 3.2 °C; RH: 50.9 ± 5.6%), (ii) BHL rose when SSC had to be interrupted, and (iii) the use of a radiant incubator prevented hypothermia and reduced dry BHL but not humid BHL (9.4 ± 1.5 kcal/kg/h; p < .001), relative to SSC (5.8 ± 2.0 kcal/kg/h; p < .001). The newborn infant's thermohygrometric environment is optimal during SSC in the delivery room. When SSC was interrupted, Ta and RH always decreased, and BHL increased in all passive environments.


Thrombospondin-1 expression in breast cancer: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components.
Thrombospondin (TSP-1) is a 450-kd adhesive glycoprotein that was initially discovered in platelets and subsequently in a variety of cell types. Several reports suggest that TSP-1 possesses tumour suppressor function, through its ability to inhibit tumour neovascularization. In this study we investigated tissue sections from 124 breast carcinomas for the immuno-histochemical expression of TSP-1 protein and its relationship to several clinicopathological parameters. The possible relationship to hormone receptors content, p53 protein, proliferation associated indices, angiogenesis, VEGF expression and extracellular matrix components (tenascin, fibronectin, laminin, collagen type IV and syndecan-1) was also estimated. TSP-1 was detected in the perivascular tissue, at the epithelial-stromal junction, in the stroma and in the tumour cells. High tumour cell TSP-1 expression was observed in 9.7%, moderate in 17.7%, mild in 10.5%, while 62.1% of the cases were negative for TSP-1 expression. The survival analysis showed an increased risk of recurrence associated with low TSP-1 tumour cell expression. High stromal TSP-1 expression was observed in 3.2% of the cases, moderate in 3.3%, mild in 27.4%, while 63.6% of the cases showed absence of TSP-1 expression. This expression was higher in invasive lobular type of breast cancer and inversely correlated with the lymph node involvement and the estrogen receptor content. Stromal TSP-1 expression was also positively correlated with extracellular matrix components expression, tenascin, fibronectin, collagen type IV, laminin, and syndecan-1. The relationship of TSP-1 expression with tumor angiogenesis, growth fraction and p53 protein expression was not significant. Our data suggest that TSP-1 expression seems to be associated with favorable biological behavior and may have clinical value in terms of predicting the risk of recurrence. In addition, TSP-1 might not be a direct anti-angiogenic factor, although it seems to be implicated in the remodeling of breast cancer tissue through interaction with other extracellular matrix components.


Colocalization and ligand-dependent discrete distribution of the estrogen receptor (ER)alpha and ERbeta.
To investigate the relationships between the loci expressing functions of estrogen receptor (ER)alpha and that of ERbeta, we analyzed the subnuclear distribution of ERalpha and ERbeta in response to ligand in single living cells using fusion proteins labeled with different spectral variants of green fluorescent protein. Upon activation with ligand treatment, fluorescent protein-tagged (FP)-ERbeta redistributed from a diffuse to discrete pattern within the nucleus, showing a similar time course as FP-ERalpha, and colocalized with FP-ERalpha in the same discrete cluster. Analysis using deletion mutants of ERalpha suggested that the ligand-dependent redistribution of ERalpha might occur through a large part of the receptor including at least the latter part of activation function (AF)-1, the DNA binding domain, nuclear matrix binding domain, and AF-2/ligand binding domain. In addition, a single AF-1 region within ERalpha homodimer, or a single DNA binding domain as well as AF-1 region within the ERalpha/ERbeta heterodimer, could be sufficient for the cluster formation. More than half of the discrete clusters of FP-ERalpha and FP-ERbeta were colocalized with hyperacetylated histone H4 and a component of the chromatin remodeling complex, Brg-1, indicating that ERs clusters might be involved in structural changes of chromatin.


Siderophile element systematics of IAB complex iron meteorites: New insights into the formation of an enigmatic group.
Siderophile trace element abundances and the 187Re-187Os isotopic systematics of the metal phases of 58 IAB complex iron meteorites were determined in order to investigate formation processes and how meteorites within chemical subgroups may be related. Close adherence of 187Re-187Os isotopic data of most IAB iron meteorites to a primordial isochron indicates that the siderophile elements of most members of the complex remained closed to elemental disturbance soon after formation. Minor, presumably late-stage open-system behavior, however, is observed in some members of the sLM, sLH, sHL, and sHH subgroups. The new siderophile element abundance data are consistent with the findings of prior studies suggesting that the IAB subgroups cannot be related to one another by any known crystallization process. Equilibrium crystallization, coupled with crystal segregation, solid-liquid mixing, and subsequent fractional crystallization can account for the siderophile element variations among meteorites within the IAB main group (MG). The data for the sLM subgroup are consistent with equilibrium crystallization, combined with crystal segregation and mixing. By contrast, the limited fractionation of siderophile elements within the sLL subgroup is consistent with metal extraction from a chondritic source with little subsequent processing. The limited data for the other subgroups were insufficient to draw robust conclusions about crystallization processes involved in their formation. Collectively, multiple formational processes are represented in the IAB complex, and modeling results suggest that fractional crystallization within the MG may have been a more significant process than has been previously recognized.


[An epidemiologic survey on blood lead levels in preschool children living in towns of Hunan Province].
To investigate blood lead levels (BLLs) and influencing factors of BLLs among preschool children living in towns of Hunan Province. A total of 2 044 preschool children (1,108 boys and 936 girls) from towns of 12 regions in Hunan Province were enrolled by a cluster sampling between September 2008 and June 2009. The average age of the children was 4.4 ± 1.1 years (range 2 to 6 years). BLLs were determined using the atomic absorption spectrographic method. The influencing factors of BLLs were investigated using a standard questionnaire and logistic regression analysis. The mean BLLs of the children were 81.9 ± 34.5 μg/L. BLLs more than 100 μg/ L were noted in 482 children (23.58%). Of the 482 children, 472 (23.09%) showed BLLs of 100-199 μg/L and 10 (0.49%) showed BLLs ≥ 200 μg/L. There were significant differences in the prevalence of elevated BLLs (≥ 100 μg/L) among different age groups (P < 0.01). The prevalence of elevated BLLs in boys (28.99%) was significantly higher than that in girls (21.98%) (P < 0.01). There were significant differences in the prevalence of elevated BLLs in children from different regions (P < 0.01). The logistic regression analysis showed that the male (OR = 1.449, P < 0.01), father's occupational lead exposure (OR = 1.314, P < 0.01)and maternal frequent use of hair dyes (OR = 1.678, P < 0.05) were risk factor for elevated BLLs. The prevalence of elevated BLLs is higher in preschool children living in towns of Hunan Province and is associated with a child's region and age. The male, father's occupational lead exposure and maternal frequent use of hair dyes are risk factor for elevated BLLs.


Bilingual listeners' perception of temporally manipulated English passages.
The current study measured, objectively and subjectively, how changes in speech rate affect recognition of English passages in bilingual listeners. Ten native monolingual, 20 English-dominant bilingual, and 20 non-English-dominant bilingual listeners repeated target words in English passages at five speech rates (unprocessed, two expanded, and two compressed), in quiet and in noise. For noise conditions, performance was measured at a signal-to-noise ratio that was determined through an adaptive procedure to avoid ceiling and floor effects. Listeners also made subjective judgments of speech rate, speech clarity, and performance confidence. In noise, stepwise improvement was observed as rate slowed down. A similar effect was not found in quiet. This pattern in performance was largely comparable across listener groups but was most robust in English-dominant listeners. Changes in speech rate and presence of noise significantly affected listeners' subjective ratings; however, no intergroup differences were observed for any of the subjective ratings. Bilingual listeners benefited from slow speech rates, more evidently so in noise than in quiet. Their performance, however, did not reach a monolingual level, even at the most favorable rate. Nonetheless, all listeners reported comparable confidence when processing temporally manipulated English passages.


[Three-dimensional reconstruction technique in gastrocnemius flap surgery: initial clinical application].
To discuss the experience with three-dimensional reconstruction technique in initial clinical application in gastrocnemius muscle flap surgery. From 2007 to 2008, 7 patients received gastrocnemius muscle flap surgeries to repair the wounds. Preoperative CT angiography or magnetic resonance imaging (MRI) was performed after injection of the contrast media for individualized three-dimensional gastrocnemius muscle flap reconstruction using Amira4.1 software. According to the size of the defect in the wound, individualized three-dimensional gastrocnemius muscle flap was designed and harvested from the posterior leg. Individualized three-dimensional reconstruction of the gastrocnemius flap was performed in 7 cases, and the reconstructed flaps clearly displayed the blood vessels, skin and the adjacent three-dimensional structures. In 6 cases the main perforating branched and trunk of the blood vessels in the designed flap were consistent with the surgical findings; in 1 case, the perforating branches failed to be clearly displayed in the designed flap, and surgical examination identified perforating branches with an average diameter of 0.5 mm (minimally 0.3 mm). The flaps survived in all the 7 cases. Three-dimensional reconstruction of the gastrocnemius flap based on the lower limb CT angiography or MRI allows three-dimensional observation of the anatomy of the flap and accurate marking of the extent of the flap to be harvested, therefore avoiding intraoperative injuries to the blood vessels to better survival of the flaps.


Bacterial Communities in the Embryo of Maize Landraces: Relation with Susceptibility to Fusarium Ear Rot.
Locally adapted maize accessions (landraces) represent an untapped resource of nutritional and resistance traits for breeding, including the shaping of distinct microbiota. Our study focused on five different maize landraces and a reference commercial hybrid, showing different susceptibility to fusarium ear rot, and whether this trait could be related to particular compositions of the bacterial microbiota in the embryo, using different approaches. Our cultivation-independent approach utilized the metabarcoding of a portion of the 16S rRNA gene to study bacterial populations in these samples. Multivariate statistical analyses indicated that the microbiota of the embryos of the accessions grouped in two different clusters: one comprising three landraces and the hybrid, one including the remaining two landraces, which showed a lower susceptibility to fusarium ear rot in field. The main discriminant between these clusters was the frequency of Firmicutes, higher in the second cluster, and this abundance was confirmed by quantification through digital PCR. The cultivation-dependent approach allowed the isolation of 70 bacterial strains, mostly Firmicutes. In vivo assays allowed the identification of five candidate biocontrol strains against fusarium ear rot. Our data revealed novel insights into the role of the maize embryo microbiota and set the stage for further studies aimed at integrating this knowledge into plant breeding programs.


Micro-computed tomography imaging and analysis in developmental biology and toxicology.
Micro-computed tomography (micro-CT) is a high resolution imaging technique that has expanded and strengthened in use since it was last reviewed in this journal in 2004. The technology has expanded to include more detailed analysis of bone, as well as soft tissues, by use of various contrast agents. It is increasingly applied to questions in developmental biology and developmental toxicology. Relatively high-throughput protocols now provide a powerful and efficient means to evaluate embryos and fetuses subjected to genetic manipulations or chemical exposures. This review provides an overview of the technology, including scanning, reconstruction, visualization, segmentation, and analysis of micro-CT generated images. This is followed by a review of more recent applications of the technology in some common laboratory species that highlight the diverse issues that can be addressed.


Arabidopsis response regulators ARR3 and ARR4 play cytokinin-independent roles in the control of circadian period.
Light and temperature are potent environmental signals used to synchronize the circadian oscillator with external time and photoperiod. Phytochrome and cryptochrome photoreceptors integrate light quantity and quality to modulate the pace and phase of the clock. PHYTOCHROME B (phyB) controls period length in red light as well as the phase of the clock in white light. phyB interacts with ARABIDOPSIS RESPONSE REGULATOR4 (ARR4) in a light-dependent manner. Accordingly, we tested ARR4 and other members of the type-A ARR family for roles in clock function and show that ARR4 and its closest relative, ARR3, act redundantly in the Arabidopsis thaliana circadian system. Loss of ARR3 and ARR4 lengthens the period of the clock even in the absence of light, demonstrating that they do so independently of active phyB. In addition, in white light, arr3,4 mutants show a leading phase similar to phyB mutants, suggesting that circadian light input is modulated by the interaction of phyB with ARR4. Although type-A ARRs are involved in cytokinin signaling, the circadian defects appear to be independent of cytokinin, as exogenous cytokinin affects the phase but not the period of the clock. Therefore, ARR3 and ARR4 are critical for proper circadian period and define an additional level of regulation of the circadian clock in Arabidopsis.


Characterization of telomere-binding activity of replication factor C large subunit p140.
The large subunit of RFC (RFC p140) has been suggested to be associated with the 3'-end of elongating DNA primer and to recruit proliferating cell nuclear antigen (PCNA) onto DNA polymerase delta. Previously, we isolated a cDNA clone encoding a DNA-binding domain of RFC p140 as a telomeric repeat (TTAGGG)n binding protein. This domain was shown to have a specific affinity for the 5'-phosphate ends of a telomere repeat sequence. In order to investigate the structure and function of RFC p140, we constructed the full-length recombinant RFC p140 as well as N- and/or C-terminal deleted mutants and analyzed their telomere-binding activities. South-Western blot and gel mobility shift analyses revealed that deletion of the N- but not the C-terminal region enhances recognition of the telomeric repeat sequence and 5'-phosphate ends, suggesting the negative effect of the N-terminal region of the RFC p140 binding to the telomeric repeat. On the other hand, the C-terminal truncated RFC inhibits the telomerase activity more than the N-terminal-deleted and full-length RFC p140. The inhibitory effect of RFC p140 on telomerase activity is completely diminished by both terminal deletions. Thus, a certain interaction of the N- and C-terminal regions is considered to be required for RFC p140 to suppress telomerase activity. Taken together, these results suggest that both telomeric repeat-binding and telomerase inhibitory activities of RFC p140 are finely regulated by the intrinsic N- and C-terminal regions.


Massive haemoperitoneum complicating metastasis in the liver.
The rare phenomenon of gross intra-abdominal bleeding due to hepatic metastasis was seen in a young male who a short time before had undergone orchiectomy because of embryonal cell carcinoma. Following laparotomy, 4 liters of fresh blood were drained from the peritoneal cavity and the left lobe of the liver, containing a single large metastasis, was removed. It is stressed that when no other cause of such haemorrhage can be found in a patient known to have had malignancy, the possibility of bleeding from a metastasis should be considered and appropriate measures taken.


Toroidal micelles of uniform size from diblock copolymers.
Uniform nanodonuts: Stable toroidal micelles that have a highly uniform size and shape spontaneously self-assemble from a selective THF/ethanol solvent mixture (see 3D AFM image). The donut-shaped micelles can be used as a template to grow gold nanoparticles, which form along the ring surface.


Pax2/5/8 and Pax6 alternative splicing events in basal chordates and vertebrates: a focus on paired box domain.
Paired box transcription factors play important role in development and tissue morphogenesis. The number of Pax homologs varies among species studied so far, due to genome and gene duplications that have affected PAX family to a great extent. Based on sequence similarity and functional domains, four Pax classes have been identified in chordates, namely Pax1/9, Pax2/5/8, Pax3/7, and Pax4/6. Numerous splicing events have been reported mainly for Pax2/5/8 and Pax6 genes. Of significant interest are those events that lead to Pax proteins with presumed novel properties, such as altered DNA-binding or transcriptional activity. In the current study, a thorough analysis of Pax2/5/8 splicing events from cephalochordates and vertebrates was performed. We focused more on Pax2/5/8 and Pax6 splicing events in which the paired domain is involved. Three new splicing events were identified in Oryzias latipes, one of which seems to be conserved in Acanthomorphata. Using representatives from deuterostome and protostome phyla, a comparative analysis of the Pax6 exon-intron structure of the paired domain was performed, during an attempt to estimate the time of appearance of the Pax6(5a) mRNA isoform. As shown in our analysis, this splicing event is characteristic of Gnathostomata and is absent in the other chordate subphyla. Moreover, expression pattern of alternative spliced variants was compared between cephalochordates and fish species. In summary, our data indicate expansion of alternative mRNA variants in paired box region of Pax2/5/8 and Pax6 genes during the course of vertebrate evolution.


Electronic conferencing for continuing medical education: a resource survey.
The use of electronic technologies to link participants for education conferences is an option for providers of Continuing Medical Education. In order to profile the kinds of electronic networks currently offering audio- or videoteleconferences for physician audiences, a survey was done during late 1985. The information collected included range of services, fees, and geographic areas served. The results show a broad diversity of providers providing both interactive and didactic programming to both physicians and other health care professionals.


Gossypol inhibits basal and estrogen-stimulated DNA synthesis in human breast carcinoma cells.
Estrogen stimulates the growth of hormone-dependent human breast cancer. Failure of chemotherapy frequently results from the development of multidrug resistance. Gossypol (GP), a naturally occurring toxin, inhibits the growth of various carcinoma cells. Thus, the effects of GP on 17 beta-estradiol (E2)-stimulated DNA synthesis were studied in two hormone-dependent human breast carcinoma cell lines: the wild-type MCF-7 and the multidrug-resistant MCF-7 Adr cells. Cells (5 x 104/well) were cultured for 24 hrs in a chemically-defined, serum-free medium consisting of 1:1 mixture of Dulbecco's Modified Eagle's medium and Ham's nutrient mixture F12 (DMEM/F12) supplemented with insulin (5.0 micrograms/ml), transferrin (5.0 micrograms/ml), epidermal growth factor (EGF; 10.0 ng/ml) and antibiotics E2 (0 or 10.0 nM), GP (0, 2.5, 5.0, 10.0 or 20.0 microM) and bovine serum albumin (BSA; 0 or 0.1 mg/ml) were used as treatments in a factorial experimental design. Cells were treated for 24 hrs and finally pulsed with 3H-thymidine (5.0 microCi/ml) for 3 hrs. E2 significantly stimulated 3H-thymidine incorporation in both MCF-7 and MCF-7 Adr cells. GP at 10.0 and 20.0 microM inhibited both basal and E2-stimulated DNA synthesis in human breast cancer cells. The inhibitory effects of GP at 10.0 microM, but not at 20.0 microM, were blocked by BSA treatment. Results from the present study indicate that GP treatment was antiproliferative in both drug-sensitive and multidrug-resistant cancer cells and that the antiproliferative effects of GP on human breast cancer cells were mediated through mechanisms independent of estrogenic responses. Thus, GP could be potentially very useful for treatment of human breast cancer patients, especially those who have developed multidrug resistance.


Long-term outcome of endoscopic shortening and stiffening of the vocal folds to raise the pitch.
In this study, we aimed to assess the long-term effects of the mucosal layer plastic surgery of the vocal folds performed on the voices of male-to-female transgenders. This retrospective cohort study enrolled 22 patients who were operated during 2004-2010 by a combined technique of transmucosal anterior suturing and stiffening of the vocal folds through a longitudinal cordotomy incision using CO2 laser. Long-term effects were assessed based on completed questionnaires on four different categories including subjective evaluation of patient's own voice perception and a standardized voice inventory (VHI), as well as an acoustic assessment and videolaryngoscopic examination. Out of the 22 patients contacted, 16 returned the questionnaires, and 13 of them participated in the subsequent acoustic analysis and videolaryngoscopic assessment. Results of the study were as follows: The total VHI score, after the procedure, was 32. F0 increased significantly for both the vowel/a/ and text from 157 to 207 Hz and 139 to 162 Hz, respectively. Perturbation measures did not show a significant change. F0 did not correlate with the VHI score. One patient had symptomatic anterior perforation that needed re-operation. The combination of transmucosal anterior suturing and stiffening of the vocal folds by laser cordectomy results in significant elevation of the F0 in the long term and in acceptable levels of VHI score compared to other reports. In conclusion, the results of the procedures show that it is enough to get the mucosal edges sutured together without the need to suture either the ligaments or the muscle of the vocal folds. The need for revision is minimal with this procedure.


Quantitative comparison of soft tissue-bone interface at chondral ligament insertions in the rabbit knee joint.
At chondral ligament insertions the calcified fibrocartilage interdigitates deeply with the lamellar bone. The shape of this interface is formed under physiological loading conditions. For the purpose of morphological comparison between different ligament entheses in the rabbit knee, the number and frequency of interdigitations and thickness of calcified fibrocartilage were quantitated at the femoral insertion of the medial collateral ligament, both insertions of the cruciate ligaments, and the tibial insertion of the patellar ligament. Among the insertions, the femoral insertion of the medial collateral ligament showed the lowest frequency and depth of interdigitations at the soft tissue-bone interface, but had the thickest zone of calcified fibrocartilage. An inverse relationship was found at the insertion interface of the cruciate and patellar ligaments. The frequency and depth of interdigations at the bone-soft tissue interface at different chondral entheses seem to be related to the mechanical strength of the respective ligament; meanwhile it may be hypothesised that the thickness of the calcified fibrocartilage might be more related to the amount of motion which takes place at an insertion.


[Characteristics of Antimony Migration and Transformation and Pollution Evaluation in a Soil-Crop System Around a Tin Mine in Hunan Province].
This study used 193 sets of farmland soil and agricultural product samples collected from around a tin mine in Hunan Province, China, to explore the antimony (Sb) content characteristics and pollution status of soil and agricultural products and to provide a scientific basis for the prevention and control of soil antimony pollution in antimony mining areas and the safe use of farmland. We analyzed the amount of antimony in the soil, basic physical and chemical properties, and antimony content in agricultural products; studied the characteristics of antimony migration and transformation in the soil-agricultural product system; and conducted safety assessments on soil and agricultural products. The results showed that the soil ω(Sb) in the central area of the mine, the southern area of the mine, the central township area, the urban-rural transfer area, and the northern area of the mine reached (2348±2165), (1298±884.1), (311.8±526.5), (302.5±355.9), and (215.6±183.2) mg·kg-1, and the exceeding multiples reached 65.22, 36.06, 8.66, 8.40, and 5.99 times, respectively. The antimony enrichment coefficients of lettuce, scallion, cabbage, water spinach, garlic, and pea seedlings in agricultural products were 0.01-0.1, which indicated good antimony absorption capacity. The antimony enrichment coefficients of loofah, asparagus lettuce, pepper, carrot, bitter gourd, corn, eggplant, cowpea, and celery were less than 0.01, and the antimony absorption capacity was relatively poor. The safety assessment results showed that roots, allium, and garlic vegetables had a high risk of antimony pollution; leafy vegetables and legumes had a higher risk of antimony pollution; and solanaceous vegetables, melons, and fruit vegetables and corn (cereals) had a high risk of antimony pollution. Therefore, it is urgent to take soil antimony pollution control measures in the mining area. At the same time, in order to realize the safe use of agricultural land in the mining area, the farmland far away from the low antimony content of the soil in the central area of the mine should be selected as the planting area, and the agricultural products with weak antimony absorption capacity should be planted first.


Single-Pill Combination of Perindopril/Indapamide/Amlodipine in Patients with Uncontrolled Hypertension: A Randomized Controlled Trial.
Patients with hypertension often require a combination of three antihypertensive agents to achieve blood pressure control, but very few single-pill triple combinations are available. The aim of this study was to determine whether a single-pill triple combination of perindopril, indapamide, and amlodipine was as effective as a dual-pill combination of perindopril/indapamide plus separate amlodipine at reducing blood pressure in patients with uncontrolled, essential hypertension. This international, multicenter, open-label, randomized controlled trial was conducted in men or women aged ≥18 years old with confirmed essential hypertension (SBP ≥140 and <160 mmHg and DBP ≥90 and <100 mmHg), uncontrolled on maximal dose antihypertensive monotherapy or with a single dose of dual therapy. Patients were randomly assigned to: single-pill triple combination of perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) or dual-pill combination perindopril 5 mg/indapamide 1.25 mg + amlodipine 5 mg (Per/Ind + Aml) once daily for 12 weeks. The primary endpoint was change in office supine SBP and DBP from baseline to week 12. The proportion of responders defined as those with normalized BP (SBP <140 mmHg and DBP <90 mmHg), and/or decrease of SBP ≥20 mmHg, and/or decrease of DBP ≥10 mmHg at week 12 (W12) compared with baseline was also assessed. Secondary efficacy endpoints included change in office supine SBP and DBP, response, and BP control at weeks 4 and 8. The tolerability of the treatments was also assessed. A total of 148 patients were randomized: 75 to Per/Ind/Aml and 73 to Per/Ind + Aml. Mean supine SBP and DBP were 149.1 ± 4.7 and 94.1 ± 3.1 mmHg, respectively, with no relevant between-group difference. At week 12, both triple-therapy regimens were associated with clinically significant reductions in SBP compared with baseline (-21.5 ± 11.7 and -20.0 ± 12.9 mmHg, respectively). Reductions in office supine DBP were also clinically significant (-15.3 ± 7.8 and -14.8 ± 9.0 mmHg, respectively). The proportion of treatment responders was high in both groups: 89.2 and 87.1%, respectively. The reduction in office supine SBP/DBP was already evident at week 4 and maintained for the duration of the study in both groups. The majority of patients were treatment responders at week 4 (89.2 and 82.9%, respectively) and had achieved BP control (87.8 vs. 78.6%, respectively), which was maintained until week 12 in both treatment groups. Both treatments were well tolerated with no between-group differences. In adult patients with uncontrolled essential hypertension on treatment, single-pill triple-combination therapy with Per/Ind/Aml is as effective as the same dose dual-pill combination of Per/Ind + Aml. Both treatments were associated with clinically significant BP reductions compared with baseline and were well tolerated. Clinical trials number: http://www.controlled-trials.com ISRCTN: 16442558. Les Laboratoires Servier.


[Communication server in the hospital--advantages, expenses and limitations].
The common situation in a hospital with multiple departments is a heterogeneous set of subsystems, one or more for each department. Today, we have a rising number of requests for an information interchange between these independent systems. The exchange of patients data has a technical and a conceptional part. Establishing a connection between more than two subsystems requires links from one system to all the others, each of them with its own code translation, interface and message transfer. A communication server is an important tool for significantly reducing the amount of work for the technical realisation. It reduces the number of interfaces, facilitates the definition, maintenance and documentation of the message structure and translation tables and helps to keep control on the message pipelines. Existing interfaces can be adapted for similar purposes. Anyway, a communication server needs a lot of configuration and it is necessary to know about low-level internetworking on different hard- and software to take advantage of its features. The code for writing files on a remote system and for process communication via TCP/IP sockets or similar techniques has to be written specifically for each communication task. There are first experiences in the university school of medicine in Mainz setting up a communication server to connect different departments. We also made a checklist for the selection of such a product.


Effects of reflective warning markers on wildlife.
Light pollution has become one of the top issues in environmental pollution, especially concerning how secondary light pollution, such as from traffic reflective materials, influences animal distribution and behavior. In this study, 15 camera traps were set up at sites with or without reflective warning markers (RWM) in coniferous forests on Cangshan Mountain located in Dali Prefecture, China. The results showed that the number of independent photographs and species at sites without RWMs were significantly higher than those at sites with RWMs. Significant differences were found between daytime and nighttime composition of bird species and non-flying mammals between two sites. This study found that RWMs had negative effects on wildlife, with the avoidance response of birds to RWMs being more obvious than that of animals at daytime. It is recommended that the use of reflective materials be carefully considered, especially in protected areas.


Characteristics of children hospitalized with severe dehydration and persistent diarrhoea in Bangladesh.
The study analyzed data from a systematic sample of children, aged less than five years, who presented with persistent diarrhoea (diarrhoea of more than 14 days duration). It aims to differentiate (a) non-severe persistent diarrhoea (with no or mild dehydration) and (b) severe persistent diarrhoea (with moderate or severe dehydration), and to identify individual characteristics associated with severe persistent diarrhoea. In total, 7,505 patients, who represented a 4% systematic sample of the patient population, were seen during January 1993-December 1995. Of them, 297 (4%) presented with persistent diarrhoea. The male:female ratio was 2:1. Eighty-three percent of them had mild or no dehydration, and 17% had moderate or severe dehydration. Severe malnutrition of the study patients defined as weight-for-age z-score < -3, weight-for-length z-score < -3 and length-for-age z-score < -3 were 33.9%, 9.7%, and 22.7% respectively. Only 3% had oedematous malnutrition, and 11% had xerophthalmia. Factors independently associated with severe persistent diarrhoea by logistic regression analyses were: number of watery stool > 10 times during the last 24 hours prior to admission (OR, 10.0; CI, 1.2-87, p = 0.03), lower respiratory tract infection (OR, 111; CI, 4.2-2955, p = 0.004), and lack of mothers' education (OR, 7.8; CI, 1.4-41.9, p = 0.016) after controlling for confounders. Awareness and health education of mothers or caregivers and better case management during acute diarrhoeal episode might prevent the development of severe persistent diarrhoea in young children. In addition, children with severe persistent diarrhoea might need special attention to have adequate rehydration and control of extraintestinal infections, including respiratory tract infection.


Addressing the Palliative Setting in Advanced Lung Cancer Should Not Remain a Barrier: A Multicenter Study.
Implementation of early palliative care (EPC) into daily oncology practice remains difficult. One of the barriers preventing oncologists from starting EPC is open communication about the palliative setting. The aim of this study was to investigate the relevance of this communication barrier. In this cross-sectional multicenter study, 106 patients with advanced thoracic cancer were issued a questionnaire to survey 3 dimensions of interest: illness understanding, observation of conversation regarding prognosis and end-of-life (EoL) care, and information preferences of the patients. Only 45% of subjects were aware that their treatment was not curative. When comparing presumed treatment goals between patients who were aware that their treatment could not cure them and patients likely to think that their treatment could cure them, 39% of the former chose quality of life versus 9% of the latter, whereas 36% of the former chose cure versus 13% of the latter (χ2 = 17.7, P = .001). Seventy-five percent never had a conversation about EoL care. More than 50% found a discussion about prognosis and EoL care to be very important. This study reveals the existence of a communication barrier and underlines the importance of sustained emphasis with regard to the palliative intent of the treatment. Patients who are aware that they could not be cured were more aware of the primary goal of their treatment, namely quality of life. Most patients did not discuss prognosis and EoL care despite their wish for such a communication.


[Protection of hypothermic preserved isolated rat hearts by resveratrol and its underlying mechanism].
To investigate whether resveratrol (RES) plays a protective role in hypothermic preserved isolated rat hearts and whether it is mediated by regulation of silent information regulator protein-1 (Sirt-1) expression. The Langendorff model of isolated rat heart was used. After stored in different Celsior solution at 4 degrees C for 9 h, SD rat hearts were randomly divided into 7 groups: blank control group;9 h group (soley hypothermic preservation for 9 h); RES group (3, 10, 30 micromol/L RES treatment plus hypothermic preservation for 9 h ), niacinamide (NAM) group (40 micromol/L NAM added in Celsior solution plus hypothermic preservation for 9 h), RES + NAM group (30 micromol/L RES and 40 micromol/L NAM were added in Celsior solution plus hypothermic preservation for 9 h). The morphological changes of cardiomyocytes were detected by the HE staining with the light microscope. The mRNA and protein expression levels of Sirt-1 were detected by Real-Time PCR and Western blot respectively. (1) Compared with the blank control group, myocardiocytes were injured remarkably in the 9 h group and the Sirt-1 mRNA and protein expression levels were decreased significantly (P < 0.01); (2) Compared with the 9 h group, rat myocardial injury was alleviated gradually in 3, 10, 30 micromol/L RES group and the Sirt-1 mRNA and protein expression levels were increased in a dose-dependent manner (P < 0.05); (3) The above protective effects of RES were attenuated by Sirt-1 inhibitor NAM. RES can protect myocardiocytes from injury caused by long range hypothermic preservation and this protective effect maybe mediated by upregulation of Sirt-1 expression.


A new flavonol glucoside from the aerial parts of Sida glutinosa.
Phytochemical investigation on the dried aerial parts of Sida glutinosa has led to the isolation of a new flavonol glucoside, glutinoside (1), along with seven known compounds, 24(28)-dehydromakisterone A (2), 1,2,3,9-tetrahydropyrrolo[2,1-b]-quinazolin-3-amine (3), docosanoic acid, 1-triacontanol, campesterol, stigmasterol, and β-sitosterol. The structures of these compounds were elucidated by means of extensive spectroscopic techniques as well as GC/MS analysis (for sterols) and comparison with the literature data. All these seven known compounds are reported from this plant for the first time.


Advanced Messaging Intervention for Medication Adherence and Clinical Outcomes Among Patients With Cancer: Randomized Controlled Trial.
Medication adherence is crucial for improving clinical outcomes in the treatment of patients with cancer. The lack of adherence and adverse drug reactions can reduce the effectiveness of cancer therapy including the quality of life. The commonly used intervention methods for medication adherence continue to evolve, and the age of fifth-generation (5G) messaging has arrived. In this study, we conducted a prospective, pilot randomized controlled trial to evaluate the effect of 5G messaging on medication adherence and clinical outcomes among patients with cancer in China. The research population was patients with nonsmall cell lung cancer undergoing pemetrexed chemotherapy who require regular folic acid (FA) and vitamin B12 supplements. The intervention and control groups were assigned to 5G messaging and second-generation (2G) messaging, respectively. The patients' medication adherence and quality of life were assessed at baseline and 1-month and 3-month time points. Moreover, the chemotherapy-related hematologic or nonhematologic toxicities, as well as the serum levels of FA and vitamin B12, were measured. Of the 567 patients assessed for eligibility between January and May 2021, a total of 154 (27.2%) patients were included. Overall, 80 were randomized to the control group and 74 to the intervention group. The odds of adherence in the 5G messaging intervention group were significantly higher than the control group at the 1-month (62/69, 90% vs 56/74, 76%; adjusted odds ratio 2.67, 95% CI 1.02-7.71) and 3-month (50/60, 83% vs 48/64, 75%; adjusted odds ratio 2.36, 95% CI 1.00-5.23) time points. Correspondingly, the FA and vitamin B12 serum levels of patients in the 5G messaging group were higher than those of the control group. Regarding hematologic toxicities, only the incidence of leukopenia in the intervention group was lower than that in the control group (25/80, 31% in the control group vs 12/74, 16% in the intervention group; P=.04). There were no differences in nonhematologic toxicities and quality of life between the 2 groups. In summary, we conclude that compared with conventional 2G text-based messaging, a 5G messaging intervention can better improve medication adherence and clinical outcome among patients with cancer. Chinese Clinical Trial Registry ChiCTR2200058188; https://www.chictr.org.cn/showproj.html?proj=164489.


Applications of 99mTc-sestamibi in oncology.
Hexakis (2-methoxyisobutylisonitrile) technetium-99m (99mTc-SestaMIBI) is a radiopharmaceutical used in nuclear medicine for myocardial perfusion imaging. In the literature different non-cardiac applications of 99mTc-SestaMIBI have been reported. Clinical studies have been performed also in non-oncologic disease (such as thyroid adenoma, diabetic foot, osteomyelitis, pulmonary actinomycosis, aneurysmal bone cyst. Sudeck's atrophy). Several models for the uptake mechanism of this radiopharmaceutical have been proposed such as binding to an 8-10 kDa cytosolic protein, simple lipid partitioning, or a membrane translocation mechanism involving diffusion and passive transmembrane distribution. Most evidence points in the direction of the third hypothesis. Many studies have indicated that uptake of hexakis (alkylisonitrile) technetium complexes is dependent on mitochondrial and plasma membrane potentials like other lipophilic cations. This explains the initial biodistribution of 99mTc-SestaMIBI to tissues with negative plasma membrane potentials and with relatively high mitochondrial content (like heart, liver, kidney and skeletal muscle tissue). Malignant tumours also possess these properties in order to maintain their increased metabolism. This behaviour encouraged the study of 99mTc-SestaMIBI as an interesting tracer imaging various tumour types: osteosarcoma, brain, lung, breast, nasopharyngeal, parathyroid and thyroid cancer. Recent research on cell cellular physiology has further revealed an active transport of 99mTc-SestaMIBI out of the tumour cells, against the potential gradient. The same mechanism is also responsible for resistance to a structurally and functionally different group of cytotoxic agents such as vinca alkaloids, epipodophyllotoxins, anthracyclins and actinomycin D. This peculiar type of resistance is due to amplification of the mammalian MDR1 gene, located on chromosome 7. For this reason the 99mTc-SestaMIBI uptake in vivo could permit the prediction of the response to the chemotherapy, when the decreased accumulation of 99mTc-SestaMIBI implies the presence of P-gp enriched tissues. In the next future a particular attention should be dedicated to this matter since one of the most important goals of the clinical trials is the demonstration of the usefulness of 99mTc-SestaMIBI for in vivo assessment of multidrug resistance.


Place learning in scopolamine-treated rats: the roles of distal cues and catecholaminergic mediation.
Experiments 1 and 2 tested the hypothesis that cholinergic receptor antagonists impair place learning in a water maze by interfering with the processing of distal, visual cues. Extramaze cues were offered to rats in the form of geometrical patterns arranged on the inner circumference of a curtain surrounding the water maze. In Experiment 1 the animals were offered both the distal cues and proximal cues in the form of pingpong balls in fixed positions on the surface of the water while only distal cues were present in Experiment 2. Animals were injected with either scopolamine (0.5 mg/kg body wt) or saline 20 min prior to the daily place learning sessions. Upon reaching criterion level performance the animals were tested on "rotation" sessions on which the distal cues were displaced. The outcome of such "rotations" demonstrated that-regardless of the presence or absence of proximal cues-scopolamine-treated rats relied at least as much as normal animals on the distal cues. The acquisition phase of both Experiments 1 and 2 demonstrated an almost complete lack of scopolamine-associated impairment in acquisition and performance of the place learning task. In Experiment 3 (when scopolamine was no longer administered) the subjects of Experiment 2 were exposed to a series of pharmacological "challenges" of their place learning performance and eventually to surgical ablation of the anteromedial prefrontal cortex. The outcome of the pharmacological challenges and the postoperative test of task performance demonstrated that the place learning performance of animals which had acquired the task under scopolamine was mediated by a neural substrate dissimilar to the substrate of task performance in normal animals. Rats acquiring the task while deprived of the cholinergic system demonstrated above-normal contributions to task mediation from catecholaminergic-probably dopaminergic-mechanisms and tentative results pointed to a "shift" toward prefrontal task mediation.


Effect of ionic stress on apoptosis and the expression of TRPM2 in human olfactory neuroepithelial-derived progenitors.
Disturbed ion homeostasis and apoptosis have been implicated in the pathophysiology of bipolar disorder (BD). TRPM2, a nonselective cation channel, is involved in apoptosis and is possibly linked with BD. In this study, monensin, a sodium ionophore, was used to model the increase [Na(+)](in) and [Ca(2+)](in) seen in BD patients. Human olfactory neuroepithelial-derived progenitors (ONP), which possess neuronal markers, were utilized to investigate the effects of monensin on apoptosis and the response of TRPM2, and the effects of lithium on the cellular response to monensin. Monensin treatment for 6 h activated caspase-3, -7 and poly(ADP-ribose) polymerase (PARP), inducing apoptosis. [Na(+)](in) increased to twice the basal level and reached steady state after 2 h of 10(-6) M monensin treatment, while [Ca(2+)](in) rose after 6 h of the treatment. Monensin treatment for 24 h decreased expression of the long form of TRPM2, and increased expression of the short form. Lithium (1 mM) pretreatment reduced the [Na(+)](in) and [Ca(2+)](in) elevation caused by monensin, down-regulated the levels of caspase-3, -7 and PARP, and reduced expression of TRPM2. Our findings suggest that the elevation of [Na(+)](in) and [Ca(2+)](in) induced ONP apoptosis and altered the expression of TRPM2. Lithium pretreatment attenuated the apoptosis induced by ionic stress.


Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration.
Etanercept and infliximab are tumor necrosis factor (TNF) antagonists that have been recently approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). This study was undertaken to investigate the occurrence of lymphoproliferative disorders in patients treated with these agents. Relevant data in the MedWatch postmarket adverse event surveillance system run by the US Food and Drug Administration were reviewed. We identified 26 cases of lymphoproliferative disorders following treatment with etanercept (18 cases) or infliximab (8 cases). The majority of cases (81%) were non-Hodgkin's lymphomas. The interval between initiation of therapy with etanercept or infliximab and the development of lymphoma was very short (median 8 weeks). In 2 instances (1 infliximab, 1 etanercept), lymphoma regression was observed following discontinuation of anti-TNF treatment, in the absence of specific cytotoxic therapy directed toward the lymphoma. Although data from a case series such as this cannot establish a clear causal relationship between exposure to these medications and the risk of lymphoproliferative disease, the known predisposition of patients with RA and CD to lymphoma, the known excess of lymphoma in other immunosuppressed populations, and the known immunosuppressive effects of the anti-TNF drugs provide a biologic basis for concern and justification for the initiation of additional epidemiologic studies to formally evaluate this possible association.


Identification and sensory evaluation of volatile compounds in oxidized porcine liver.
Headspace solid phase microextraction (HS-SPME) was used to isolate the off-flavor volatile compounds, which are formed during the oxidation of porcine liver induced by iron. Poly(dimethylsiloxane)/divinylbenzene fiber was used in the HS-SPME. Changes in the volatile compounds of oxidized porcine liver and unsaturated fatty acids induced by iron were examined. Results showed that 1-octen-3-one (metallic), hexanol (weak metallic), 1-octen-3-ol (mushroomlike), (E)-2-nonenal (cardboardlike), and (E,E)-2,4-decadienal (fatty, oily) were the main contributors to the overall off-flavor of porcine liver. The results of the sensory evaluation revealed that oxidized arachidonic acid has a major impact on metallic and liverlike off-flavor and that when liverlike off-flavor is perceived, metallic is also included. Oxidized linolenic acid was the most important contributor to the objectionable fishy off-flavor. Oxidized porcine liver exhibited distinct metallic, liverlike, and weak fishy background notes. Liverlike flavor had a high correlation coefficient with odor characteristics such as metallic (0.839) and fishy (0.777). In this study, it was clearly observed that the stronger the metallic and fishy off-flavor the higher the perception of liverlike off-flavor.


The presence of desmosine and isodesmosine in eggshell membrane protein.
Investigation of eggshell membrane by amino acid analysis and radioimmunoassay established the presence of the crosslinking amino acids desmosine and isodesmosine at levels of 28 microgram/100 mg dry weight. Specific enzymatic and chemical hydrolysis indicates that these crosslinks are present as constituents of eggshell membrane protein and do not reflect the presence of small amounts of elastin. The eggshell membrane protein has approximately 10 times the level of lysine-derived aldehyde found in elastin.


Pathway to nursing for urban core youth.
The issue of diversity in the workforce as one component of a nursing workforce shortage is a growing problem. Underrepresentation of minority nurses in clinical settings is also suspected to play a role in low patient satisfaction with health care. After holding a focus group of local high school students and their parents, a school of nursing located in an urban core developed an outreach program to help increase the enrollment of students from the urban core, and to help assure that they are prepared in every way to persist to graduation. This intervention program is described in this article.


Separation in Logistic Regression: Causes, Consequences, and Control.
Separation is encountered in regression models with a discrete outcome (such as logistic regression) where the covariates perfectly predict the outcome. It is most frequent under the same conditions that lead to small-sample and sparse-data bias, such as presence of a rare outcome, rare exposures, highly correlated covariates, or covariates with strong effects. In theory, separation will produce infinite estimates for some coefficients. In practice, however, separation may be unnoticed or mishandled because of software limits in recognizing and handling the problem and in notifying the user. We discuss causes of separation in logistic regression and describe how common software packages deal with it. We then describe methods that remove separation, focusing on the same penalized-likelihood techniques used to address more general sparse-data problems. These methods improve accuracy, avoid software problems, and allow interpretation as Bayesian analyses with weakly informative priors. We discuss likelihood penalties, including some that can be implemented easily with any software package, and their relative advantages and disadvantages. We provide an illustration of ideas and methods using data from a case-control study of contraceptive practices and urinary tract infection.


Self-limiting nitrogen/hydrogen plasma radical chemistry in plasma-enhanced atomic layer deposition of cobalt.
Cobalt (Co) is a potential candidate in replacing copper for interconnects and has been applied in trenches in the semiconductor industry for over twenty years. A non-oxidizing reactant is required in the plasma-enhanced atomic layer deposition (PE-ALD) of thin films of metals to avoid O-contamination. PE-ALD of Co has been demonstrated experimentally with plasma sources of NH3 or a mixture of N2 and H2, but the growth mechanism and key reactions are not clear. In this study, we have investigated the reactions of plasma-generated predominant species, i.e. radicals ˙H, ˙N, ˙NH and ˙NH2, at metal precursor (CoCp2) treated Co(001) and Co(100) surfaces using static DFT calculations at 0 K and molecular dynamics simulations at 600 K. The proposed reaction mechanisms are (1) ˙N radicals play an important role in eliminating the surface-bound Cp ligand (if any) via pyridine (C5H5N) formation and desorption, whereas ˙H radicals have endothermic reactions for eliminating the Cp ligand via CpH formation and desorption; (2) the surface NHx species are eliminated by ˙H radicals via NH3 formation and desorption. The simulations of these key reactions show that on the Co(001) surface, the remaining Cp ligand and surface NHx species after the metal precursor pulse will be completely removed with ˙N and ˙H radicals, resulting in Co atoms deposited on the Co(001) surface at a coverage of 3.03 Co nm-2. However, on the Co(100) surface, the surface NH2 species cannot be completely removed via NH3 formation and desorption due to overall endothermic reactions. Instead, ˙H radicals react with trench N species, resulting from H transfer in the metal precursor pulse, to form NH. These trench N species cannot be eliminated completely on the Co(100) surface, which will be the source of N impurities in the deposited Co thin films. At the post-plasma stage, the metal surface will be covered with NHx-terminations with plasma generated ˙NH radicals and is then ready for the next deposition cycle. Our DFT results highlight and explain why ammonia or H2/N2 plasma, which produce NHx species, are required to deposit high-quality and low-impurity Co thin films using Co metallocene precursors.


The nurse case manager in acute care settings. Job description and function.
Nurse administrators face many decisions about the emerging role of the nurse case manager (NCM). Who should be the NCM? What are the skills needed? How should the professional nurse function in the new role? The author reports the results of a study that helps answer these questions.


β1 integrin targeting potentiates antiangiogenic therapy and inhibits the growth of bevacizumab-resistant glioblastoma.
Antiangiogenic therapies like bevacizumab offer promise for cancer treatment, but acquired resistance, which often includes an aggressive mesenchymal phenotype, can limit the use of these agents. Upregulation of β1 integrin (ITGB1) occurs in some bevacizumab-resistant glioblastomas (BRG) whereby, mediating tumor-microenvironment interactions, we hypothesized that it may mediate a mesenchymal-type resistance to antiangiogenic therapy. Immunostaining analyses of β1 integrin and its downstream effector kinase FAK revealed upregulation in 75% and 86% of BRGs, respectively, compared with pretreatment paired specimens. Furthermore, flow cytometry revealed eight-fold more β1 integrin in primary BRG cells compared with cells from bevacizumab-naïve glioblastomas (BNG). Fluorescence recovery after photobleaching of cells engineered to express a β1-GFP fusion protein indicated that the mobile β1 integrin fraction was doubled, and half-life of β1 integrin turnover in focal adhesions was reduced markedly in BRG cells compared with bevacizumab-responsive glioblastoma multiforme cells. Hypoxia, which was increased with acquisition of bevacizumab resistance, was associated with increased β1 integrin expression in cultured BNG cells. BRGs displayed an aggressive mesenchymal-like phenotype in vitro. We found that growth of BRG xenograft tumors was attenuated by the β1 antibody, OS2966, allowing a 20-fold dose reduction of bevacizumab per cycle in this model. Intracranial delivery of OS2966 through osmotic pumps over 28 days increased tumor cell apoptosis, decreased tumor cell invasiveness, and blunted the mesenchymal morphology of tumor cells. We concluded that β1 integrin upregulation in BRGs likely reflects an onset of hypoxia caused by antiangiogenic therapy, and that β1 inhibition is well tolerated in vivo as a tractable strategy to disrupt resistance to this therapy.


[Syndrome differentiation-based treatment with traditional Chinese medicine for proteinuria in patients with chronic kidney disease: a randomized multicenter trial].
To evaluate the clinical efficacy of syndrome differentiation-based treatment with traditional Chinese medicine (TCM) versus losartan therapy in addition to basic treatment for management of proteinuria in patients with chronic kidney disease. This multicenter, randomized, and case-controlled clinical trial was conducted among 81 consecutive patients meeting the inclusion criteria. The patients were randomized consecutively to receive TCM treatments according to the syndrome patterns in TCM (spleen and kidney Qi and Yin deficiency, and spleen and kidney Qi and Yang deficiency, n=60) or oral losartan therapy (50 mg/day, n=21) in addition to the basic treatments. All the patients were followed up for 24 weeks to observe the clinical effects. The patients in TCM group showed a significantly higher overall response rate (93.33%) than those in losartan group (76.20%, P<0.05). The TCM score in the two groups were all decreased at week 24 as compared with baseline (P<0.01 or P<0.05). The TCM scores in both groups decreased significantly after the treatments as compared with the baseline scores (P<0.05). After a 8-week-long treatment, Scr, eGFR and Cys-C, U-Pro/24 h, and MA/Cr all decreased significantly in TCM group (P<0.05) but showed no significant changes in losartan group (P>0.05). Syndrome differentiation-based TCM treatment in addition to basic treatments can produce satisfactory therapeutic effects on proteinuria in patients with chronic kidney disease by improving the clinical symptoms, reducing TCM symptom scores and proteinuria, and protecting the renal functions.


Cryostorage of cloned amino Acid analog-resistant carrot and tobacco suspension cultures.
Five clones were isolated from five different amino acid analog-resistant Daucus carota L. var. Sativa and Nicotiana tabacum L. cv. Xanthi cell lines. The individual clones were similar in their resistance to dl-5-methyltryptophan, S-(2-aminoethyl)-l-cysteine, or azetidine-2-carboxylic acid, and in their corresponding free amino acid levels.The cell suspensions were stored using a controlled freezing rate at -196 degrees C with concentrations up to 40% of the four cryoprotectants: mannitol, proline, dimethylsulfoxide, glycerol, and combinations of dimethyl-sulfoxide and glycerol. No less than 55% post-thaw viability, determined by phenosafranin dye exclusion, was obtained after storage using a cryoprotectant mixture of 10% glycerol and 10% dimethylsulfoxide. Growth of the cryostored cells could be obtained consistently only by using feeder plate methodology with this combination of cryoprotectants. Post-thaw viability and percentage of cells demonstrating growth, as estimated by growth kinetics, were found to be similar. This indicates that little selection occurred during the freezing and recovery process. In addition, the amino acid analog-resistant traits were unaltered following cryostorage.Suspension cultures of Datura innoxia Mill. were frozen similarly with maximum post-thaw viability of 38%, but subsequent growth was not obtained.Protoplasts of D. innoxia, tobacco and carrot were also cryostored using a mixture of 10% dimethylsulfoxide and 10% glycerol as cryoprotectants. Viabilities of no less than 40% were obtained, however, only the carrot protoplasts regenerated cell walls and underwent cell division.


Immune reconstitution inflammatory syndrome in HIV-infected patients with disseminated histoplasmosis.
Four HIV-1-infected patients presented with unusual clinical manifestations in the course of disseminated histoplasmosis, including liver abscesses, compressive lymphadenitis, intestinal obstruction, uveitis and arthritis within a median of 45 days after initiation of highly active antiretroviral therapy (HAART). They had a median increase of 106 CD4 cells/mul and granulomas with caseation in three. Partial immune reconstitution induced by HAART during disseminated histoplasmosis either related to the variety capsulatum or duboisii may be associated with immune reconstitution inflammatory syndrome.


The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds.
Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-atom macrocycle rather than typical trithiazolylpyridine cores embedded in 26-atom and 29-atom peptide macrocycles. We describe the cloning of an 11-gene berninamycin cluster from Streptomyces bernensis UC 5144, its heterologous expression in Streptomyces lividans TK24 and Streptomyces venezuelae ATCC 10712, and detection of variant and incompletely processed scaffolds. Posttranslational maturation in S. lividans of both the wild-type berninamycin prepeptide (BerA) and also a T3A mutant generates macrocyclic compounds as well as linear variants, which have failed to form the pyridine and the macrocycle. Expression of the gene cluster in S. venezuelae generates a variant of the 35-atom skeleton of berninamycin, containing a methyloxazoline in the place of a methyloxazole within the macrocyclic framework.


Actinium-225 in targeted alpha-particle therapeutic applications.
Alpha particle-emitting isotopes are being investigated in radioimmunotherapeutic applications because of their unparalleled cytotoxicity when targeted to cancer and their relative lack of toxicity towards untargeted normal tissue. Actinium- 225 has been developed into potent targeting drug constructs and is in clinical use against acute myelogenous leukemia. The key properties of the alpha particles generated by 225Ac are the following: i) limited range in tissue of a few cell diameters; ii) high linear energy transfer leading to dense radiation damage along each alpha track; iii) a 10 day halflife; and iv) four net alpha particles emitted per decay. Targeting 225Ac-drug constructs have potential in the treatment of cancer.


[Variations of the frequency of the diagnosis of depression in Chile].
Different publications have found an increase of depression diagnostic during last years. In this work chilean information available for the last decade in different hospitals (psychiatric, no psychiatric, public-private) is reviewed. Results confirm an increase of relative frequency of depressive disorders according to different classifications systems. Sex differences and possible explanations for this variation in diagnostic frequency are analyzed. Clinical practice would be the principal variable in this modifications.


Two-phase anaerobic digestion of the organic fraction of municipal solid waste: estimation of methane production.
Energy generation from methane (CH(4)) is one of the primary targets of the anaerobic digestion process. Consequently, the focus of this study was to investigate the effect on CH(4) production of total solids (TS) loading (measured as % TS) and hydraulic residence time (HRT) during the treatment of the organic fraction of municipal solid waste (OFMSW). Laboratory-scale, two-phase anaerobic digestion systems were employed with each system consisting of an acidogenic reactor and a methanogenic reactor linked in series. The group A runs in the experiment explored the effect on digester performance of four variations in methanogenic HRT (15, 20, 25 and 30 days) at three different feed TS concentrations (8, 12 and 15%). The group B runs compared the actual methane yield (0.14 to 0.45 L g VSfeed−1)) to that predicted by the Chen-Hashimoto model. Results from the group A runs indicated that acidogenesis improved with an increase in % TS and a decrease in HRT; while, methanogenesis behaved inversely, achieving higher yields at the lower % TS and longer HRT values. In comparison with the group B runs, the Chen-Hashimoto model under-predicted (by an average of 16.5 ± 6.6%) the CH(4) yield obtained from the digestion of OFMSW.


Presence in peripheral blood of healthy individuals of autoreactive T cells to a membrane antigen present on bone marrow-derived cells.
Intrathymic clonal deletion is thought to be the major mechanism responsible for tolerance to nonsequestered antigens such as the ones expressed by bone marrow-derived cells. In the case of sequestered antigens that potentially do not come in contact with T cells in the thymus, it is thought that autoreactive T cells are present in periphery but are tightly regulated to prevent autoimmune disease. Indeed, autoreactive T cells to sequestered antigens can be isolated in healthy individuals. However, the presence of autoreactive T cells to nonsequestered circulating antigens had not been observed. In this report, we present evidence for the presence, in the periphery of all healthy individuals tested (n = 25), of autoreactive T cells to GpIIb-IIIa, a membrane antigen present on bone marrow-derived cells that is expressed on circulating platelets and on the cell surface of the epithelial cells of the thymic stroma early in intrauterine life. Using an in vitro T-cell proliferation assay, we have demonstrated that activation of these specific GpIIb-IIIa autoreactive alpha beta TCR+ CD4+ CD8- T cells requires internalization and processing of the GpIIb-IIIa by antigen-presenting cells and its presentation by HLA-DR class II molecules in the presence of exogenous interleukin 2 (IL-2). This indicates that some autoreactive T cells directed against membrane antigens present on bone marrow-derived cells and also expressed in the thymus are not necessarily eliminated by intrathymic deletion.


Ulnar variance in scaphoid nonunion.
Negative ulnar variance can be a risk factor in Kienböck's disease, wrist instability, and scaphoid bone fracture. This study focused on the ulnar variance in wrists with scaphoid bone nonunion. We retrospectively reviewed posteroanterior wrist radiographs of 65 patients who were diagnosed as established scaphoid nonunion and underwent open reduction and bone grafting between 2005 and 2010. We used reference radiographs from contralateral wrists of 65 consecutive skeletally- mature patients with distal radius fracture as the control group and then measured ulnar variance and compared it in both groups. Ulnar variance was measured in standard posteroanterior wrist X-rays of 65 scaphoid nonunion and 65 normal controls. Twenty five patients (38.5%) in the scaphoid nonunion group had negative ulnar variance, and the mean value was -0.26 (± 1.24) mm (range: -3, +2). In the control group, 15 subjects (23.1 %) had an ulnar minus wrist, and the mean ulnar variance was + 0.54 (± 1.47) mm (range: -3, +4) .The difference in ulnar variance was significant between the two groups (P-value = 0.001). Ulnar variance may influence developing of nonunion process in scaphoid bone fracture.


Evaluation of the severity of ulcerative colitis using endoscopic dual red imaging targeting deep vessels.
Background and study aims Colonoscopies can predict long-term prognoses in patients with ulcerative colitis (UC). Recently, a new imaging technology has been developed that uses 3 types of illumination with center wavelengths of 540 nm, 600 nm, and 630 nm. The use of both the 600-nm and 630-nm lights (Dual red imaging; DRI) is critical for identifying blood vessels in deeper tissue. The aim of this study was to evaluate the usefulness of DRI for assessing the severity of inflammation in patients with UC. Patients and methods A total of 43 UC patients were retrospectively enrolled to evaluate the endoscopic severity of 112 colon segments, and Mayo endoscopic scores, DRI scores and the severity of inflammation on a visual analogue scale (VAS) were compared. The Mayo endoscopic scores, DRI scores, and histologic scores were evaluated, and the interobserver agreement on DRI scores among 5 investigators was also assessed. The usefulness of DRI scores for predicting prognoses was also assessed in patients with clinical remission. Results The DRI scores were closely correlated with the VAS for the severity of colonic inflammation (r = 0.96) and the histologic scores (r = 0.72 - 0.8). The DRI scores had a higher rate of interobserver agreement (κ values = 0.63 - 0.88) than the Mayo endoscopic scores (κ values = 0.44 - 0.59). Inter-observer agreement between 4 non-experts was also excellent (mean κ value = 0.76, range 0.63 - 0.82). The expected time until recurrence was significantly longer in patients with lower DRI scores (P < 0.01). Conclusion DRI can be used in patients with mild to moderate endoscopic severity because it targets the deep vascular pattern. The prognosis of UC can be predicted by assessing deep vessels using DRI.


A Density Functional Theory Investigation of Nin , Pdn , and Ptn Clusters (n=1-4) Adsorbed on Buckminsterfullerene.
In this study, we examine the adsorptions of Ni, Pd, and Pt clusters on C60 by using a computational approach. Our calculation results show that the base structure of C60 can host Nin /Pdn /Ptn (n=1-4) clusters with good adsorption stability and the complexes establish either two or no unpaired electrons. The binding energy of Pd and Pt clusters increases as the number of metal atoms increases, implying that the coverage of C60 with Pd or Pt preferentially establishes a large-size metal cluster. A single metal atom favorably occupies the C-C bridge site. For dimer clusters, the three metals of interest share a similar binding fashion, in which two metal atoms establish direct interactions with the C-C bridge sites. For trimer adsorptions, the formation of linear and triangular structures is observed. Both Pt3 and Ni3 preferably constitute isosceles triangles on C60 , whilst Pd3 favorably establishes a linear shape. Finally, for each of the Ni4 and Pd4 adsorption cases, we observed three stable binding configurations: rhombus, tetrahedron, and Y-form. Whereas Ni4 establishes a tetrahedral form, Pd4 attains the most stable form with the Y-shape geometry on C60 . Overall, we observe that the trend of Pd binding to C60 tends to go beyond the fashion of Ni and Pt. In terms of magnetic alignment, the Pdn -C60 systems seem to be non-magnetic in most cases, unlike the Ni and Pt cases, the structures of which possess magnetic moments of 2 μB in their most stable forms.


Distributed Particle Filter for Target Tracking: With Reduced Sensor Communications.
For efficient and accurate estimation of the location of objects, a network of sensors can be used to detect and track targets in a distributed manner. In nonlinear and/or non-Gaussian dynamic models, distributed particle filtering methods are commonly applied to develop target tracking algorithms. An important consideration in developing a distributed particle filtering algorithm in wireless sensor networks is reducing the size of data exchanged among the sensors because of power and bandwidth constraints. In this paper, we propose a distributed particle filtering algorithm with the objective of reducing the overhead data that is communicated among the sensors. In our algorithm, the sensors exchange information to collaboratively compute the global likelihood function that encompasses the contribution of the measurements towards building the global posterior density of the unknown location parameters. Each sensor, using its own measurement, computes its local likelihood function and approximates it using a Gaussian function. The sensors then propagate only the mean and the covariance of their approximated likelihood functions to other sensors, reducing the communication overhead. The global likelihood function is computed collaboratively from the parameters of the local likelihood functions using an average consensus filter or a forward-backward propagation information exchange strategy.


Poor glycaemic control and arrhythmias.
To evaluate number, type, and complexity of arrhythmias in diabetics compared with controls and, among diabetics, comparing good glycaemic control (GGC) and poor glycaemic control (PGC) patients. We compared Ambulatory Electrocardiogram recordings of 92 diabetics and 100 controls. The glycaemic profile of 50 diabetics, taken the same day as the Ambulatory ECG recording, was subdivided into GGC (gluco-stick mean values between 100 and 140 mg/dL) or PGC (gluco-stick values ≤99 mg/dL in 3-of-4 daily determination or gluco-stick values ≥140 mg/dL in 3-of-4 daily determination). Diabetics show a higher prevalence of either ventricular ectopic beats (VEBs) (93.47% vs. 82% controls, p < 0.05) and heart rate (both in sinus rhythm and in atrial fibrillation) (98.35 ± 10 beats/min in diabetics vs. 78.10 ± 8.1 in controls, p < 0.001). Moreover, diabetics with PGC show either a higher prevalence of VEBs (96.42% vs 77.27% in GGC, p < 0.05) and of supraventricular ectopic beats (SVEBs) (96.42% vs. 68.18 in GGC, p < 0.05); furthermore, diabetics with PGC show more severe and complex atrial and ventricular arrhythmias (SVEBs 32.14% vs 0%, p < 0.05; VEBs 39.28% vs 9.09%, p < 0.05). The analysis of our sample shows that the arrhythmogenic condition is not only provided from diabetic condition per se but it is enhanced in PGC. Infact PGC patients showed higher number of VEBs, often polymorphic, expression of more severe arrhythmic and cardiovascular outcome. This could be partially explained by hyperactivation of autonomic nervous system during metabolic stress (which increases mean heart rate). Moreover more severe diabetic patients may present coronary microangiopathy that can further explain their arrhythmogenic tendency.


Composition and volume of fluid swallowed by fetal sheep.
Oesophageal cannulations were performed in seven fetal sheep between 109 and 128 d of gestation. Fluid swallowed by the fetuses was collected externally and periodically returned to the fetal stomach by a peristaltic pump. The volume of fluid swallowed daily was calculated from the movement of water in a parallel pump circuit. Samples of oesophageal fluid were removed from the collection bag at the same time as tracheal and amniotic fluid samples. Oesophageal fluid was very viscous and was usually intermediate in colour between tracheal and amniotic fluids. After reduction of viscosity by dithiothreitol, the compositions of the three fluids were analysed. Mean concentrations of Na+, Cl- and protein, and mean osmolarity of oesophageal fluid, were intermediate between values obtained in tracheal and amniotic fluids. [K+] was often greater in oesophageal fluid than would be expected by the relative contribution of tracheal and amniotic fluids as indicated by [Na+] and [Cl-] in the three fluids. It is suggested that the high viscosity of oesophageal fluid and its relatively high [K+] may result from fetal salivary secretions. Ionic concentrations in individual sets of samples show that the proportions of tracheal and amniotic fluids swallowed by the fetus are variable from day to day. The mean daily volumes of fluid swallowed by the seven fetuses ranged from 98 to 577 ml, and are in agreement with previously published data.


[Primary large cell neuroendocrine carcinoma of the urinary bladder].
Large cell neuroendocrine carcinoma of the urinary bladder is rare. In the last five years, we have had the opportunity to see this type of cancer in an 88-year-old and in a 66-year-old males. In both cases, transurethral resection of carcinoma of the bladder was carried out. In the first case, urothelial carcinoma was detected and deeper in the bladder wall, large cell neuroendocrine carcinoma structures were found. In the second case, the bladder was only infiltrated with large cell neuroendocrine carcinoma. Both tumors expressed NSE, CD56 and synaptophysin. Other markers, such as those against calcitonin, chromogranin, PP, VIP, serotonin, gastrin, glucagon and somatostatin did not react with the tumor. In the first case, no tumor dissemination was found; in the second case, clinical methods confirmed dissemination into the liver, left adrenal gland, spleen and paracaval lymph nodes. Given his age, the first patient only received symptomatic therapy. The other patient underwent chemotherapy and his condition is stable. Paraneoplastic manifestations of the tumors were not clinically found. Histogenetic origin of neuroendocrine tumors is not fully clarified. In some cases, tumor development is thought to be associated with Brunns nests, cystitis cystica and urothelial carcinoma stem cells.


Shorter incubation period is associated with severe disease progression in patients with COVID-19.
The diagnosed COVID-19 cases revealed that the incubation periods (IP) varied a lot among patients. However, few studies had emphasized on the different clinical features and prognosis of patients with different IP. A total of 330 patients with laboratory-confirmed COVID-19 were enrolled and classified into immediate onset group(IP<3 days, I group, 57 cases) and late onset group(IP>10 days, L group, 75 cases) based on IP. The difference of clinical characteristics and prognosis of the two groups were compared. There were more patients with fever in I group than in L group(P = 0.003), and counts of all the total lymphocytes, total T lymphocytes, CD4 + and CD8 + T lymphocytes were significantly different between the two groups(all P < 0.01). Besides, patients in L group had more GGOs in CT scan than I group and there were more patients in I group receiving antibiotic treatment than in L group(P < 0.001). For disease aggravation, the median CT scores were comparable between the two groups, but individually, there were more patients with increased CT score during hospitalization in I group than in L group. The aggravation incidence of CT presentation was 21.1% in I group, significantly higher than L group(8.0%, P = 0.042). Multivariable COX models suggested that IP was the only independent factors for CT aggravation. Conclusively, patients with different IP were different in clinical symptoms, laboratory tests, and CT presentations. Shorter IP was associated with the aggravation of lung involvement in CT scan.


Association of serotypes of Streptococcus pneumoniae with age in invasive pneumococcal disease.
A total of 7,764 isolates from patients with invasive pneumococcal disease (IPD) were collected from 1992 to June 2006. Data on serotypes were available for 5,022 isolates (64.7% of all invasive isolates). Some 54.0% of the isolates originated from adults >or=16 years of age, and 46.0% were from children <16 years of age. The leading serotypes were 14, 23F, 1, 6B, 7F, 3, and 4. The serotypes significantly more common in children were 14, 6B, 19F, and 18C, while among adults, serotypes 3 and 4 were predominant. Serotype 7F was statistically more prevalent among children <4 months old than among the other age groups. Among children aged >or=4 months and <1 year, serotype 19F occurred statistically more frequently; and among children aged >or=1 year to <5 years, serotypes 14, 6B, and 18C were overrepresented. The serotypes predominantly affecting patients younger than the remaining collective of patients were 14, 6B, 19F, and 18C, while patients with IPD caused by serotypes 3, 4, and 9V were older than the collective, on average.


[Oropharyngeal dysphagia in patients with multiple sclerosis].
The aim of this study is to evaluate the prevalence of the clinical and videofluoroscopic (VDF) symptoms of oropharyngeal dysphagia in patients with multiple sclerosis, and to describe its therapeutic management. We studied 23 patients suffering from multiple sclerosis to evaluate the characteristics of the disease, the VDF exploration of swallowing and therapeutic strategies. The VDF exploration enables us to define the VDF symptoms that assess the safety and efficiency of swallowing for the oral and pharyngeal phases. The therapeutic strategies include: changes in the characteristics of the diet, changes of posture and active manoeuvres. The patients studied presented a mean EDSS score 7.4 (4-9). There were alterations in swallowing efficiency and/or safety in more than 80% of the patients. In 52% there was some change in the swallowing safety. 40% of them were silent aspirators. All these patients were fed orally without any complications, in 78% the volume of the bolus has been modified and changes have taken place in the consistency (thickening for liquids); in 43%, moreover, postural strategies were employed and active manoeuvres (supraglottic swallow) were introduced in 13% in order to improve swallowing safety. There is a high prevalence of clinical and VDF symptoms of oropharyngeal dysphagia in patients with advanced multiple sclerosis. VDF enables us to diagnose the pathophysiological mechanism of aspiration and the existence of silent aspirators, and helps us to introduce specific therapeutic interventions for each patient, thereby achieving safe and efficient swallowing, while prolonging oral feeding.


On-Skin Triboelectric Nanogenerator and Self-Powered Sensor with Ultrathin Thickness and High Stretchability.
Researchers have devoted a lot of efforts on pursuing light weight and high flexibility for the wearable electronics, which also requires the related energy harvesting devices to have ultrathin thickness and high stretchability. Hence, an elastic triboelectric nanogenerator (TENG) is proposed that can serve as the second skin on human body. The total thickness of this TENG is about 102 µm and the device can work durably under a strain of 100%. The carbon grease is painted on the surface of elastomer film to work as stretchable electrode and thus the fine geometry control of the electrode can be achieved. This elastic TENG can even work on the human fingers without disturbing body movement. The open-circuit voltage and short-circuit current from the device with a contact area of 9 cm2 can reach 115 V and 3 µA, respectively. Two kinds of self-powered sensor systems with optimized identification strategies are also designed to demonstrate the application possibility of this elastic TENG. The superior characteristics of ultrathin thickness, high stretchability, and fine geometry control of this TENG can promote many potential applications in the field of wearable self-powered sensory system, electronics skin, artificial muscles, and soft robotics.


Nonesterified fatty acid content of rabbit kidney cortex slices after warm ischemia and low temperature preservation.
Nonesterified fatty acid content (NEFA) of rabbit kidney cortex slices preserved at low temperature after warm ischemia was examined. Kidney tissue slices were subjected to 60 min of warm (37 degrees C) ischemia induced by anoxic gaseous phase incubation and then either had reperfusion simulated by normothermic oxygenated aqueous incubation or were preserved at 5 degrees C up to 18 h with UW sodium gluconate solution and then reincubated at normothermia. Slice NEFA content increased during ischemia and remained significantly higher than controls during simulated reperfusion. Ischemic tissue slice NEFA content was significantly reduced by both 3- and 18-h preservations. There was a significant increase in NEFA content in 3-h preserved slices during simulated reperfusion. This increase was relatively unaffected by the addition of KCN to the incubation medium, suggesting that mitochondrial injury was induced by ultrashort preservation of ischemic tissue slices. Ischemic tissue slices preserved for 18 h increased in NEFA content during simulated reperfusion but did not appear more damaged than slices subjected to ischemia alone. Addition of quinacrine (100 micromol/l) to the cold preservation solution significantly reduced NEFA content during simulated reperfusion of slices preserved both 3 and 18 h with a greater effect in 18-h preserved slices. Quinacrine had no effect when added only during simulated reperfusion. KCN addition during simulated reperfusion indicated that quinacrine acted as a mitochondrial protectant in the absence of phospholipase inhibition under these conditions. This study showed that cold preservation may be useful for resuscitation of ischemic tissues harvested for transplantation. Treatments administered during cold preservation of ischemic tissue can have a lasting beneficial effect during reperfusion and may be more effective than similar treatments given only during reperfusion.


Development and commissioning of a Monte Carlo photon beam model for the forthcoming clinical trials in microbeam radiation therapy.
A new radiotherapy technique, named microbeam radiation therapy (MRT), is under development at the ID17 Biomedical Beamline of the European Synchrotron Radiation Facility (ESRF). This innovative method is based on the fact that normal tissue can withstand high radiation doses in small volumes without any significant damage. The promising results obtained in the preclinical studies have paved the way to forthcoming clinical trials, which are currently in preparation. Highly accurate dose calculations at the treatment planning stage are required in this context. The aims of this study are the development and experimental benchmarking of a photon beam source model, which will be the core of the future MRT treatment planning system (TPS). The ID17 x-ray source was modeled by the synchrotron ray tracing code SHADOW. The Monte Carlo (MC) simulation code PENELOPE/PENEASY was employed to transport the photon beam from the source to the patient position through all the beamline components. The phase-space state variables of the particles reaching the patient position were used as an input to generate a photon beam model. Computed dose distributions in a homogeneous media were experimentally verified by using Gafchromic(®) films in a solid-water phantom. Benchmarking was split into two phases. First, the lateral dose profiles and the percentage depth-dose (PDD) curves in the broad beam configuration were considered. The acceptability criteria for radiotherapy dose computations recommended by international protocols such as the Technical Reports Series 430 (TRS 430) of the International Atomic Energy Agency (IAEA) were used. Second, the analogous dosimetric magnitudes in MRT irradiations, i.e., PDD of the central microbeam and the corresponding peak-to-valley dose ratios (PVDR) were evaluated and compared with MC calculations. A full characterization of the ID17 Biomedical Beamline (ESRF) synchrotron x-ray source and the development of an accurate photon beam model were achieved in this work. Calculated and experimental dose distributions agreed to within the recommended acceptability criteria described in international codes of practice (TRS 430) for broad beam irradiations. The overall deviation in low gradient areas amounted to 2%-3%. The maximum distance-to-agreement in high gradient regions was lower than 0.7 mm. MC calculations also reproduced MRT experimental results within uncertainty bars. These results validate the photon beam model for its use in MRT radiation therapy calculations. The first MC synchrotron photon beam model for MRT irradiations that reproduces experimental dose distributions in homogeneous media has been developed. This beam model will constitute an essential component of the TPS calculation engine for patient dose computation in forthcoming MRT clinical trials.


Solute Accumulation in Tobacco Cells Adapted to NaCl.
Cells of Nicotiana tabacum L. var Wisconsin 38 adapted to NaCl (up to 428 millimolar) which have undergone extensive osmotic adjustment accumulated Na(+) and Cl(-) as principal solutes for this adjustment. Although the intracellular concentrations of Na(+) and Cl(-) correlated well with the level of adaptation, these ions apparently did not contribute to the osmotic adjustment which occurred during a culture growth cycle, because the concentrations of Na(+) and Cl(-) did not increase during the period of most active osmotic adjustment. The average intracellular concentrations of soluble sugars and total free amino acids increased as a function of the level of adaptation; however, the levels of these solutes did not approach those observed for Na(+) and Cl(-). The concentration of proline was positively correlated with cell osmotic potential, accumulating to an average concentration of 129 millimolar in cells adapted to 428 millimolar NaCl and representing about 80% of the total free amino acid pool as compared to an average of 0.29 millimolar and about 4% of the pool in unadapted cells. These results indicate that although Na(+) and Cl(-) are principal components of osmotic adjustment, organic solutes also may make significant contributions.


Selection of nuclear genotypes associated with the thermo-sensitivity of Owen-type cytoplasmic male sterility in sugar beet (Beta vulgaris L.).
Cytoplasmic male sterility in sugar beet becomes thermo-sensitive when combined with specific genotypes, potentially offering a means to environmentally control pollination by this trait. The stability of cytoplasmic male sterility expression in several genetic backgrounds was investigated in sugar beet (Beta vulgaris L.). Nine genetically heterogenous plants from open-pollinated varieties were crossed with a cytoplasmic male sterile line to obtain 266 F1 plants. Based on marker analysis using a multiallelic DNA marker linked to restorer-of-fertility 1 (Rf1), we divided the F1 plants into 15 genotypes. We evaluated the phenotypes of the F1 plants under two environmental conditions: greenhouse rooms with or without daytime heating during the flowering season. Three phenotypic groups appeared: those consistently expressing male sterility, those consistently having restored pollen fertility, and those expressing male sterility in a thermo-sensitive manner. All plants in the consistently male sterile group inherited a specific Rf1 marker type named p4. We tested the potential for thermo-sensitive male sterile plants to serve as seed parents for hybrid seed production, and three genotypes were selected. Open pollination by a pollen parental line with a dominant trait of red-pigmented hypocotyls and leaf veins resulted in seed setting on thermo-sensitive male sterile plants, indicating that their female organs were functional. More than 99.9% of the progeny expressed the red pigmentation trait; hence, highly pure hybrids were obtained. We determined the nucleotide sequences of Rf1 from the three genotypes: One had a novel allele and two had known alleles, of which one was reported to have been selected previously as a non-restoring allele at a single U.S. breeding station but not at other stations in the U.S., or in Europe or Japan, suggesting environmental sensitivity.


Cancer incidence in California flight attendants (United States).
To examine unusual exposure opportunities to flight crews from chemicals, cosmic radiation, and electric and magnetic fields. This project evaluated the incidence of cancers of the breast and other sites among Association of Flight Attendants (AFA) members residing in California. AFA membership files were matched to California's statewide cancer registry to identify a total of 129 newly diagnosed invasive cancers among AFA members with California residential histories between 1988 and 1995. Compared to the general population, female breast cancer incidence was over 30% higher than expected, and malignant melanoma incidence was roughly twice that expected. Both of these are cancers that are associated with higher socioeconomic status and have been suggestively associated with various sources of radiation. Consistent with the results from Nordic studies of cabin crews and a recent meta-analysis of prior studies, these data suggest that follow-up investigations should focus on the potential relative contribution of workplace exposures and lifestyle characteristics to the higher rates of disease for these two cancers.